Duchenne muscular dystrophy with adrenal insufficiency and glycerol kinase deficiency: high resolution cytogenetic analysis with molecular, biochemical, and clinical studies.

A syndrome of Duchenne muscular dystrophy (DMD), adrenal hypoplasia, glycerol kinase deficiency, and mental retardation has been recognised. We report a further case ascertained from a history of DMD, severe mental retardation, and an Addison-like disorder. Cytogenetic analysis of the proband revealed an interstitial deletion of the short arm of the X chromosome. from Xp21.1 to Xp22.11, comprising about 9% of the length of the normal X chromosome. His mother was heterozygous for the deletion, but his maternal grandmother and sister both had two normal X chromosomes. DNA probe analysis confirmed the existence of a deletion in the affected boy, as probes 754, C7, XJ1-1, and pERT87 consistently failed to hybridize to his DNA. His sister was heterozygous for the RFLP associated with 754, thus confirming that she had two normal X chromosomes. There was no evidence of chronic granulomatous disease, other immunological defect, or retinitis pigmentosa in this case. Biochemical studies revealed gross glyceroluria and hyperglycerolaemia, indicating glycerol kinase deficiency which has been confirmed enzymatically. We have subsequently screened 21 other boys with DMD for glyceroluria and found one other case. Cytogenetic analysis has also been performed in nine other families, where a boy with DMD has been shown to have a deletion of DNA sequences localised to the region Xp21. None of these cases demonstrated any cytogenetic abnormality, nor has their clinical course been unusual.

A syndrome of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

,

    adrenal hypoplasia
    SYMPTOMS

,

    glycerol kinase deficiency
    BIOCHEMICAL

, and

    mental retardation
    SYMPTOMS

 has been recognised. We report a further case ascertained from a history of

    DMD
    DIAGNOSIS

,

    severe mental retardation
    SYMPTOMS

, and an

    Addison-like disorder
    DIAGNOSIS

.

    Cytogenetic analysis
    PARACLINICAL

 of the proband revealed an

    interstitial deletion of the short arm of the X chromosome. from Xp21.1 to Xp22.11, comprising about 9% of the length of the normal X chromosome
    GENETICS

.

    His
    GENDER

    mother was heterozygous for the deletion
    FAMILY

, but

    his maternal grandmother and sister both had two normal X chromosomes
    FAMILY

.

    DNA probe analysis
    PARACLINICAL

 confirmed the

    existence of a deletion in the
    GENETICS

 affected

    boy
    GENDER

, as

    probes 754, C7, XJ1-1, and pERT87 consistently failed to hybridize to his DNA
    NEG_FINDINGS

.

    His
    GENDER

    sister was heterozygous for the RFLP associated with 754
    FAMILY

, thus confirming that

    she
    GENDER

    had two normal X chromosomes
    FAMILY

. There was

    no evidence of chronic granulomatous disease, other immunological defect
    NEG_FINDINGS

, or

    retinitis pigmentosa
    NEG_FINDINGS

 in this case.

    Biochemical studies
    PARACLINICAL

 revealed

    gross glyceroluria
    BIOCHEMICAL

 and

    hyperglycerolaemia
    BIOCHEMICAL

, indicating

    glycerol kinase deficiency
    BIOCHEMICAL

 which has been confirmed enzymatically. We have subsequently screened 21 other

    boys
    GENDER

 with

    DMD
    DIAGNOSIS

 for

    glyceroluria
    DIAGNOSIS

 and found one other case.

    Cytogenetic analysis
    PARACLINICAL

 has also been performed in nine other families, where a

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 has been shown to have a

    deletion of DNA sequences localised to the region Xp21
    GENETICS

. None of these cases demonstrated any

    cytogenetic abnormality
    NEG_FINDINGS

, nor has their clinical course been unusual.

Duchenne muscular dystrophy (DMD)
DMD
Addison-like disorder
DMD
glyceroluria
DMD

adrenal hypoplasia
mental retardation
severe mental retardation

glycerol kinase deficiency
gross glyceroluria
hyperglycerolaemia
glycerol kinase deficiency


Duchenne muscular dystrophy in one of monozygotic twin girls.

Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy. Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids made between cells derived from each girl and a mouse line suggest that in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that both girls are heterozygous for Duchenne muscular dystrophy. X inactivation, by chance, resulted in two contrasting cell masses with different active X chromosomes. This segregation was followed by, and may even have resulted in, twinning into a female pair, one normal and one with the full clinical features of the disease.

    Monozygotic twin girls
    FAMILY

 are reported, one of whom has the

    typical clinical features of Duchenne muscular dystrophy
    SYMPTOMS

 despite a

    normal female karyotype
    NEG_FINDINGS

. Although certain features of the biopsy

    were atypical
    NEG_FINDINGS

, the clinical diagnosis was supported by

    persistent markedly raised blood creatine kinase levels
    BIOCHEMICAL

 and

    findings typical of DMD
    SYMPTOMS

 on

    electromyography
    PARACLINICAL

 and

    magnetic resonance spectroscopy
    PARACLINICAL

.

    Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids
    PARACLINICAL

 made between cells derived from each

    girl
    GENDER

 and a mouse line suggest that

    in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived
    FAMILY

. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that

    both girls
    FAMILY

    are heterozygous for Duchenne muscular dystrophy
    FAMILY

.

    X inactivation
    GENETICS

, by chance, resulted in

    two contrasting cell masses with different active X chromosomes
    MICROSCOPIC

. This segregation was followed by, and may even have resulted in,

    twinning into a female pair, one normal and one with the full clinical features of the disease
    FAMILY

.


Duchenne muscular dystrophy in a girl with a 45,X/46,XX/47,XXX chromosome constitution.

We report on a 4-year-old girl with Duchenne muscular dystrophy (DMD). One of her sisters had grossly elevated serum creatine-kinase and pyruvate-kinase levels, and one of her maternal great uncles was presumptively affected by DMD. Cytogenetic analysis showed a 45,X/46,XX/47,XXX chromosome constitution. The maternally inherited DMD gene is presumed to be present on the single X of the 45,X cell line.

We report on a

    4-year-old
    AGE

    girl
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

.

    One of her sisters had grossly elevated serum creatine-kinase and pyruvate-kinase levels
    FAMILY

, and

    one of her maternal great uncles was presumptively affected by DMD
    FAMILY

.

    Cytogenetic analysis
    PARACLINICAL

 showed a

    45,X/46,XX/47,XXX chromosome constitution
    GENETICS

.

    The maternally inherited DMD gene is presumed to be present on the single X of the 45,X cell line.
    GENETICS


Duchenne muscular dystrophy in a girl with an (X;15) translocation.

This is a report of a girl with Duchenne muscular dystrophy (DMD) associated with an 46,X,t (X;15) (p21; q 26) chromosome constitution. Although in the eight published cases of girls with DMD and a t(X;aut) different autosomes were involved in the translocation, the breakpoint was always at Xp21. The present case supports the hypothesis that the DMD gene must be located at Xp21. In this study, involvement of the father's chromosomes in the translocation was detected.

This is a report of a

    girl
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 associated with an

    46,X,t (X;15) (p21; q 26) chromosome constitution
    GENETICS

. Although in the eight published cases of

    girls
    GENDER

 with

    DMD
    DIAGNOSIS

 and a

    t(X;aut) different autosomes were involved in the translocation
    GENETICS

, the

    breakpoint was always at Xp21
    GENETICS

. The present case supports the hypothesis that the

    DMD gene must be located at Xp21
    GENETICS

. In this study,

    involvement of the father's chromosomes in the translocation
    FAMILY

 was detected.


De novo DNA microdeletion in a girl with Turner syndrome and Duchenne muscular dystrophy.

The single X chromosome of a girl with Turner syndrome (45,X) and typical Duchenne muscular dystrophy was investigated at the chromosomal and DNA levels. No visible abnormality of the residual X chromosome was found upon high-resolution R-banding. The DNA was analysed by Southern blotting and hybridization with seven cloned probes mapping in the Xp21 region where the Duchenne locus is thought to be located. A molecular deletion was detected with probes pERT 87.1, pERT 87.8, and pERT 87.15. The other probes (754, C7, 99.6, and RC8) gave a normal signal. The DNA alleles seen in the two parents indicated that the deletion found in the propositus had occurred de novo on a maternal X chromosome.

The

    single X chromosome
    GENETICS

 of a

    girl
    GENDER

 with

    Turner syndrome (45,X)
    DIAGNOSIS

 and

    typical Duchenne muscular dystrophy
    DIAGNOSIS

 was investigated at the

    chromosomal and DNA levels
    PARACLINICAL

.

    No visible abnormality of the residual X chromosome
    NEG_FINDINGS

 was found upon

    high-resolution R-banding
    PARACLINICAL

. The

    DNA was analysed
    PARACLINICAL

 by

    Southern blotting and hybridization with seven cloned probes mapping in the Xp21 region where the Duchenne locus is
    PARACLINICAL

 thought to be located. A

    molecular deletion was
    GENETICS

 detected with

    probes pERT 87.1, pERT 87.8, and pERT 87.15
    GENETICS

. The other probes (754, C7, 99.6, and RC8)

    gave a normal signal
    NEG_FINDINGS

.

    The DNA alleles seen in the two parents indicated that the deletion found in the propositus had occurred de novo on a maternal X chromosome
    FAMILY

.

Turner syndrome (45,X)
typical Duchenne muscular dystrophy


Infantile facioscapulohumeral muscular dystrophy: new observations.

Clinical, electrodiagnostic, and biopsy findings in a family with infantile facioscapulohumeral muscular dystrophy are reported. Four of eight family members having the disorder, all with onset in infancy, developed severe weakness leading to death in adolescence. The clinical course and prognosis of infantile facioscapulohumeral muscular dystrophy may, therefore, be as devastating as that of Duchenne muscular dystrophy. The unusual infantile presentation and high mortality in our affected family members suggest that the gene coding for this disorder may be different from that responsible for conventional facioscapulohumeral muscular dystrophy.

Clinical,

    electrodiagnostic, and biopsy
    PARACLINICAL

 findings in a family with

    infantile facioscapulohumeral muscular dystrophy
    DIAGNOSIS

 are reported. Four of eight

    family members having the disorder
    FAMILY

, all with onset in

    infancy
    AGE

, developed

    severe weakness
    SYMPTOMS

 leading to

    death
    SYMPTOMS

    in adolescence
    AGE

. The clinical course and prognosis of

    infantile facioscapulohumeral muscular dystrophy
    DIAGNOSIS

 may, therefore, be as devastating as that of

    Duchenne muscular dystrophy
    DIAGNOSIS

. The

    unusual infantile presentation
    SYMPTOMS

 and

    high mortality
    SYMPTOMS

 in our

    affected family members
    FAMILY

 suggest that the

    gene coding for
    GENETICS

 this disorder may be different from that responsible for

    conventional facioscapulohumeral muscular dystrophy
    DIAGNOSIS

.

severe weakness
death
unusual infantile presentation
high mortality


Duchenne muscular dystrophy and malignant hyperthermia--two case reports.

The case histories are presented including the anaesthetic and postoperative management, of two children, a two-year-old with undiagnosed Duchenne muscular dystrophy (DMD) and a three-year-old with known DMD. The child with undiagnosed DMD had no symptoms of DMD and had received halothane twice before, without succinylcholine, with no apparent difficulty. Following an uneventful induction of anaesthesia with halothane, nitrous oxide and O2, succinylcholine resulted in bilateral masseter muscle spasm and then, in rapid sequence, ventricular tachycardia and cardiac arrest. Resuscitation was difficult, prolonged and associated with hyperkalaemia (K+ = 12.57 mEq X L-1), severe metabolic and respiratory acidosis, high peripheral venous pressure and massive hepatosplenomegaly, but not hyperthermia. The patient was finally resuscitated but died two days later. Skeletal muscle biopsy results were consistent with malignant hyperthermia. The second patient was known to have DMD but did not receive prophylactic or intraoperative dantrolene nor have his anaesthetic machine flushed with oxygen for an extended period prior to induction of anaesthesia. This child was anaesthetized with fentanyl and N2O and, with the exception of a high intraoperative heart rate (155-160 beats X min-1), had an uncomplicated anaesthetic and operation (intraoperative axillary temperatures ranged between 36.8-37.9 degrees C). Postoperatively his temperature rapidly increased to 38.8 degrees C and then 40.3 degrees C and he became metabolically acidotic. Intravenous administration of dantrolene for 48 hours reduced the temperature and allowed normal recovery and discharge. A postoperative muscle biopsy was consistent with DMD.(ABSTRACT TRUNCATED AT 250 WORDS)

The case histories are presented including the anaesthetic and postoperative management, of two

    children
    AGE

, a

    two-year-old
    AGE

 with

    undiagnosed Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 and a

    three-year-old
    AGE

 with

    known DMD
    DIAGNOSIS

. The

    child
    AGE

 with

    undiagnosed DMD
    DIAGNOSIS

 had

    no symptoms of DMD
    NEG_FINDINGS

 and had

    received halothane twice before
    MEDICATION

,

    without succinylcholine
    MEDICATION

, with

    no apparent difficulty
    NEG_FINDINGS

. Following an

    uneventful induction of anaesthesia with halothane, nitrous oxide and O2
    MEDICATION

,

    succinylcholine
    MEDICATION

 resulted in

    bilateral masseter muscle spasm
    SYMPTOMS

 and then, in rapid sequence,

    ventricular tachycardia
    SYMPTOMS

 and

    cardiac arrest
    SYMPTOMS

.

    Resuscitation
    PARACLINICAL

 was difficult, prolonged and associated with

    hyperkalaemia (K+ = 12.57 mEq X L-1)
    BIOCHEMICAL

,

    severe metabolic and respiratory acidosis
    SYMPTOMS

,

    high peripheral venous pressure
    SYMPTOMS

 and

    massive hepatosplenomegaly
    SYMPTOMS

, but

    not hyperthermia
    NEG_FINDINGS

. The patient was finally

    resuscitated
    MEDICATION

 but

    died
    SYMPTOMS

 two days later.

    Skeletal muscle biopsy results
    PARACLINICAL

 were consistent with

    malignant hyperthermia
    DIAGNOSIS

. The second patient was known to have

    DMD
    DIAGNOSIS

 but

    did not receive prophylactic or intraoperative dantrolene
    NEG_FINDINGS

    nor have his anaesthetic machine flushed with oxygen for an extended period prior to induction of anaesthesia
    MEDICATION

. This

    child
    AGE

 was

    anaesthetized with fentanyl and N2O
    MEDICATION

 and, with the exception of a

    high intraoperative heart rate (155-160 beats X min-1)
    SYMPTOMS

, had an

    uncomplicated anaesthetic and operation
    MEDICATION

 (

    intraoperative axillary temperatures ranged between 36.8-37.9 degrees C)
    SYMPTOMS

. Postoperatively his

    temperature rapidly increased to 38.8 degrees C and then 40.3 degrees C
    SYMPTOMS

 and

    he
    GENDER

 became

    metabolically acidotic
    BIOCHEMICAL

.

    Intravenous administration of dantrolene for 48 hours
    MEDICATION

    reduced the temperature
    SYMPTOMS

 and allowed

    normal recovery and discharge
    SYMPTOMS

. A

    postoperative muscle biopsy
    PARACLINICAL

 was consistent with DMD.(ABSTRACT TRUNCATED AT 250 WORDS)

hyperkalaemia (K+ = 12.57 mEq X L-1)
metabolically acidotic


Treatment of Duchenne muscular dystrophy with growth hormone inhibitors.

A controlled, double-blind therapeutic trial with the drug mazindol, a growth hormone inhibitor, was performed in a pair of 7 1/2 year-old monozygotic twins, with Duchenne muscular dystrophy (DMD). The rationale for this trial was based on a patient (reported previously) affected simultaneously with DMD and growth hormone (GH) deficiency, who is showing a benign course of the dystrophic process and is still walking at 18 years. One of the twins received 2 mg of mazindol daily, while the other received a placebo. The assessment, repeated every 2 months, included weight and height measurements, functional and motor ability tests, ergometry and determinations of serum enzymes and GH levels. After one year of trial the code was broken and it was seen that the twin under placebo treatment was strikingly worse than his brother, the progression of whose condition was practically arrested. These results strongly suggest that treatment with a GH inhibitor is beneficial for DMD patients.

A controlled, double-blind

    therapeutic trial with the drug mazindol, a growth hormone inhibitor
    MEDICATION

, was performed in a pair of

    7 1/2 year-old
    AGE

    monozygotic twins
    FAMILY

, with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. The rationale for this trial was based on a patient (reported previously)

    affected simultaneously with DMD
    FAMILY

 and

    growth hormone (GH) deficiency
    BIOCHEMICAL

, who is showing a

    benign course of the dystrophic process
    SYMPTOMS

 and is still walking

    at 18 years
    AGE

. One of the

    twins received 2 mg of mazindol daily
    MEDICATION

, while the other received a placebo. The assessment, repeated every 2 months, included

    weight and height measurements
    PARACLINICAL

,

    functional and motor ability tests
    PARACLINICAL

,

    ergometry
    PARACLINICAL

 and

    determinations of serum enzymes and GH levels
    PARACLINICAL

. After one year of trial the code was broken and it was seen that

    the twin under placebo treatment
    FAMILY

    was strikingly worse than his brother, the progression of whose condition was practically arrested
    FAMILY

. These results strongly suggest that

    treatment with a GH inhibitor
    MEDICATION

 is beneficial for

    DMD
    DIAGNOSIS

 patients.


Xp21/autosome translocations. Case report and risk for Duchenne muscular dystrophy.

An isolated case of Duchenne muscular dystrophy in a 15-year-old retarded girl with a de novo t(X;2) (p21.2;q37) translocation is described. Her clinical history is presented, with particular emphasis on CK level determinations made at several different times during her development. The similarities between this patient and previously reported females with Duchenne muscular dystrophy are discussed with reference to de novo translocations with a breakpoint at Xp21 and the risk of DMD in such females.

An isolated case of

    Duchenne muscular dystrophy
    DIAGNOSIS

 in a

    15-year-old
    AGE

    retarded
    AGE

    girl
    GENDER

 with a

    de novo t(X;2) (p21.2;q37) translocation
    GENETICS

 is described.

    Her
    GENDER

 clinical history is presented, with particular emphasis on

    CK level determinations
    PARACLINICAL

 made at several different times during her development. The similarities between this patient and previously reported

    females
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 are discussed with reference to

    de novo translocations with a breakpoint at Xp21
    GENETICS

 and the risk of

    DMD
    DIAGNOSIS

 in such

    females
    GENDER

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy
DMD


Cytogenetic analysis and muscle differentiation in a girl with severe muscular dystrophy.

The uncommon case is described of a girl severely affected with Duchenne muscular dystrophy. Cytogenetic analysis revealed no numerical or structural abnormalities of the X-chromosome in any of the cells examined (leucocytes and myoblasts). No abnormality in morphology, growth pattern or differentiation was observed in the dystrophic muscle cultures as compared with control cultures.

The uncommon case is described of a

    girl
    GENDER

 severely affected with

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Cytogenetic analysis
    PARACLINICAL

 revealed

    no numerical or structural abnormalities of the X-chromosome in any of the cells examined (leucocytes and myoblasts)
    NEG_FINDINGS

.

    No abnormality in morphology, growth pattern or differentiation was observed in the dystrophic muscle cultures
    NEG_FINDINGS

 as compared with control cultures.


Duchenne muscular dystrophy due to familial Xp21 deletion detectable by DNA analysis and flow cytometry.

We report two male cousins with Duchenne muscular dystrophy (DMD) in whom cytogenetic studies have shown a small interstitial deletion at Xp21. The lesion is readily detectable in patients and carriers by flow cytometry which indicates that approximately 6000 kb of DNA are deleted in each case. The DNA markers OTC, C7, and B24 are present in the deleted X chromosome but 87-8, 87-1, and 754 are absent. Despite apparently identical deletions one affected boy has profound mental handicap while the other is only mildly retarded. The results confirm the assignment of familial DMD to Xp21 and illustrate the value of flow cytometry in improving the precision of chromosome analysis. We have also undertaken flow cytometry in a cell line from a previously reported DMD patient with a de novo Xp21 deletion who had, in addition, chronic granulomatous disease, retinitis pigmentosa, and the McLeod syndrome. The results indicate that the amount of DNA deleted from the X is similar in both families despite the striking differences in phenotype.

We report two

    male
    GENDER

    cousins with Duchenne muscular dystrophy (DMD)
    FAMILY

 in whom

    cytogenetic studies
    PARACLINICAL

 have shown a

    small interstitial deletion at Xp21
    GENETICS

. The lesion is readily detectable in patients and carriers by

    flow cytometry
    PARACLINICAL

 which indicates that

    approximately 6000 kb of DNA are deleted
    GENETICS

 in each case.

    The DNA markers OTC, C7, and B24 are present in the deleted X chromosome but 87-8, 87-1, and 754 are absent
    GENETICS

.

    Despite apparently identical deletions
    FAMILY

 one affected

    boy
    GENDER

 has

    profound mental handicap
    SYMPTOMS

 while the other is

    only mildly retarded
    SYMPTOMS

. The results confirm the assignment of

    familial DMD
    GENETICS

 to

    Xp21
    GENETICS

 and illustrate the value of

    flow cytometry
    PARACLINICAL

 in improving the precision of

    chromosome analysis
    PARACLINICAL

. We have also undertaken

    flow cytometry
    PARACLINICAL

 in a cell line from a previously reported

    DMD
    DIAGNOSIS

 patient with a

    de novo Xp21 deletion
    GENETICS

 who had, in addition,

    chronic granulomatous disease
    DIAGNOSIS

,

    retinitis pigmentosa
    DIAGNOSIS

, and the

    McLeod syndrome
    DIAGNOSIS

. The results indicate that the

    amount of DNA deleted from the X
    GENETICS

 is similar in both families despite the striking differences in phenotype.

profound mental handicap
only mildly retarded

DMD
chronic granulomatous disease
retinitis pigmentosa
McLeod syndrome


Results of manual resistance exercise on a manifesting carrier of Duchenne muscular dystrophy. A case report.

This case report is about a manifesting carrier of Duchenne muscular dystrophy who participated in a program of maximal concentric-eccentric manual resistance exercise three days each week for 12 weeks. As a consequence, she achieved mean strength increases exceeding 28% bilaterally. She also ceased falling, which she had been experiencing several times a month before beginning the exercise program.

This case report is about a manifesting carrier of

    Duchenne muscular dystrophy
    DIAGNOSIS

 who

    participated in a program of maximal concentric-eccentric manual resistance exercise three days each week for 12 weeks
    MEDICATION

. As a consequence,

    she
    GENDER

 achieved

    mean strength increases exceeding 28% bilaterally
    SYMPTOMS

.

    She
    GENDER

 also

    ceased falling
    SYMPTOMS

, which

    she
    GENDER

 had been experiencing several times a month before beginning the

    exercise program
    MEDICATION

.


Duchenne muscular dystrophy in a 46 XY female.

The most common muscular dystrophy, Duchenne muscular dystrophy (DMD), is an X-linked disorder that ordinarily has full clinical expression only in males. Reports of typical clinical features in females are rare but have occurred with a phenotypically identical autosomal recessive muscular dystrophy as well as in females with X-chromosome abnormalities such as the Turner syndrome. A girl with full expression of DMD due to a 46 XY karyotype is reported, and other clinical conditions in which expression of the DMD gene occurs in females are reviewed.

The most common

    muscular dystrophy
    DIAGNOSIS

,

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, is an

    X-linked disorder
    GENETICS

 that ordinarily has full clinical expression only in

    males
    GENDER

. Reports of typical clinical features in

    females
    GENDER

 are rare but have occurred with a phenotypically identical

    autosomal recessive muscular dystrophy
    DIAGNOSIS

 as well as in

    females
    GENDER

 with

    X-chromosome abnormalities
    GENETICS

 such as the

    Turner syndrome
    DIAGNOSIS

. A

    girl
    GENDER

 with

    full expression of DMD
    GENETICS

 due to a

    46 XY karyotype
    GENETICS

 is reported, and other clinical conditions in which

    expression of the DMD gene
    GENETICS

 occurs in

    females
    GENDER

 are reviewed.

muscular dystrophy
Duchenne muscular dystrophy (DMD)
autosomal recessive muscular dystrophy
Turner syndrome

X-linked disorder
X-chromosome abnormalities
full expression of DMD
46 XY karyotype
expression of the DMD gene


Duchenne muscular dystrophy in a female with a translocation involving Xp21.

A female with Duchenne muscular dystrophy, diagnosed at the age of 3 years 8 months, is reported. Chromosome studies revealed an X;autosome reciprocal translocation t(X;5) (p21.2;q31.2). With the BrdU-Hoechst 33258-Giemsa technique, there was nonrandom preferential inactivation of the normal X. Our patient is the ninth reported case of Duchenne muscular dystrophy associated with an X;autosome translocation. In all cases the breakpoint in the X chromosome is in band p21 at or near the site of the DMD gene.

A

    female
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

, diagnosed at the

    age of 3 years 8 months
    AGE

, is reported.

    Chromosome studies
    PARACLINICAL

 revealed an

    X;autosome reciprocal translocation t(X;5) (p21.2;q31.2)
    GENETICS

. With the

    BrdU-Hoechst 33258-Giemsa technique
    PARACLINICAL

, there was nonrandom preferential inactivation of the normal X. Our patient is the ninth reported case of

    Duchenne muscular dystrophy
    DIAGNOSIS

 associated with an

    X;autosome translocation
    GENETICS

. In all cases the

    breakpoint in the X chromosome is in band p21 at or near the site of the DMD gene
    GENETICS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy


Deletion on the X chromosome detected by direct DNA analysis in one of two unrelated boys with glycerol kinase deficiency, adrenal hypoplasia, and Duchenne muscular dystrophy.

In studies of the X chromosomes of two unrelated boys with adrenal hypoplasia, glycerol kinase deficiency, Duchenne muscular dystrophy, and mental retardation, conventional G banding did not reveal any numerical or structural abnormality, but direct DNA analysis with the X short-arm probes 754, C7, and OCT revealed a deletion in 1 of these patients. It is likely that both boys have a deletion at Xp21 affecting a number of closely linked disease-specific gene loci.

In

    studies of the X chromosomes
    PARACLINICAL

 of two unrelated

    boys
    GENDER

 with

    adrenal hypoplasia
    SYMPTOMS

,

    glycerol kinase deficiency
    BIOCHEMICAL

,

    Duchenne muscular dystrophy
    DIAGNOSIS

, and

    mental retardation
    SYMPTOMS

,

    conventional G banding
    PARACLINICAL

    did not reveal any numerical or structural abnormality
    NEG_FINDINGS

, but

    direct DNA analysis with the X short-arm probes 754, C7, and OCT
    PARACLINICAL

 revealed a deletion in 1 of these patients. It is likely that both

    boys
    GENDER

 have a

    deletion at Xp21 affecting a number of closely linked disease-specific gene loci
    GENETICS

.


Clinical and genetic studies of muscular dystrophy in young girls.

During the years 1971-81, we treated 7 girls with clinical features suggestive of Duchenne dystrophy. Muscle weakness developed at 1.5 or at 5-8 years and progressed rapidly. Two girls were in wheel-chairs in their teens. Muscle atrophy began in the proximal parts of the lower extremities and pseudohypertrophy of the calf occurred in all patients. Serum creatine phosphokinase (CPK) activity was moderately to highly elevated in all cases and EMG showed a moderate to marked myopathic pattern. Chromosomal studies showed normal finding in the five examined. Mental retardation (IQ 37-73) was present in four. Consanguinity was present in 3 out of the 7 cases. Two mothers showed elevated levels of CPK and myopathic patterns on EMG. In addition, one mother had slight muscle weakness at the age of 42 and another had prominent pseudohypertrophy of the calf. Sex-linked recessive inheritance might be considered here, because carriers of autosomal recessive type never showed elevated levels of CPK or mild myopathic symptoms. The other five of our seven might be cases of autosomal recessive inheritance, because the mothers had normal serum CPK levels and in 2 families there was a consanguinity.

During the years 1971-81, we treated 7

    girls
    GENDER

 with clinical features suggestive of

    Duchenne dystrophy
    DIAGNOSIS

.

    Muscle weakness
    SYMPTOMS

 developed

    at 1.5 or at 5-8 years
    AGE

 and progressed rapidly. Two

    girls
    GENDER

 were

    in wheel-chairs
    MEDICATION

    in their teens
    AGE

.

    Muscle atrophy began in the proximal parts of the lower extremities
    SYMPTOMS

 and

    pseudohypertrophy of the calf
    SYMPTOMS

 occurred in all patients.

    Serum creatine phosphokinase (CPK) activity was moderately to highly elevated
    BIOCHEMICAL

 in all cases and

    EMG
    PARACLINICAL

 showed a

    moderate to marked myopathic pattern
    SYMPTOMS

.

    Chromosomal studies showed normal finding
    NEG_FINDINGS

 in the five examined.

    Mental retardation (IQ 37-73)
    SYMPTOMS

 was present in four.

    Consanguinity was present in
    FAMILY

 3 out of the 7 cases. Two

    mothers
    GENDER

 showed

    elevated levels of CPK
    BIOCHEMICAL

 and

    myopathic patterns on EMG
    SYMPTOMS

. In addition, one

    mother
    GENDER

 had

    slight muscle weakness
    SYMPTOMS

    at the age of 42
    AGE

 and another had

    prominent pseudohypertrophy of the calf
    SYMPTOMS

.

    Sex-linked recessive inheritance
    GENETICS

 might be considered here, because

    carriers of autosomal recessive type
    GENETICS

 never showed

    elevated levels of CPK
    BIOCHEMICAL

 or

    mild myopathic symptoms
    NEG_FINDINGS

. The other five of our seven might be cases of

    autosomal recessive inheritance
    GENETICS

, because the

    mothers had normal serum CPK levels
    FAMILY

 and

    in 2 families there was a consanguinity
    FAMILY

.

Sex-linked recessive inheritance
carriers of autosomal recessive type
autosomal recessive inheritance


Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy. Seventeen cases in eight families including an autopsied case.

A new type of progressive muscular dystrophy, autosomal recessive distal muscular dystrophy, is described, based on observations on 17 cases (8 males and 9 females) in 8 families, including an autopsied case. The disease developed in young adults. Muscle weakness and atrophy were most marked in the distal parts of the legs, especially in the gastrocnemius and soleus muscles, and then spread to the thighs and gluteal muscles. Early impairment of standing on tip-toe with retention of the ability to stand on the heels was conspicuous. Difficulty in climbing stairs, standing up and walking subsequently appeared, but rarely progressed to confinement to bed. The forearms became mildly atrophic, with decrease in grip strength, but the small hand muscles were spared. The EMG showed myopathic changes and nerve conduction was normal. Serum creatine kinase activity was characteristically increased up to 100-fold in the early stages of the disease. It was also markedly increased in subjects in the preclinical stage and mildly in some heterozygotes. Muscle biopsies revealed myopathic changes with severe segmental necrosis accompanied by regeneration. The changes were similar to those of Duchenne muscular dystrophy. An autopsied case, aged 68 years, showed generalized muscle abnormalities with a distal predominance. The muscles in the lower legs, especially those of the calves, were severely affected. No lesions were found in the brain, spinal cord or peripheral nerves.

A new

    type of progressive muscular dystrophy
    DIAGNOSIS

,

    autosomal recessive distal muscular dystrophy
    DIAGNOSIS

, is described, based on observations on 17 cases (8

    males
    GENDER

 and 9

    females
    GENDER

) in 8 families, including an

    autopsied
    PARACLINICAL

 case. The disease developed in

    young adults
    AGE

.

    Muscle weakness and atrophy were most marked in the distal parts of the legs, especially in the gastrocnemius and soleus muscles
    SYMPTOMS

, and then

    spread to the thighs and gluteal muscles
    SYMPTOMS

.

    Early impairment of standing on tip-toe
    SYMPTOMS

 with

    retention of the ability to stand on the heels
    SYMPTOMS

 was conspicuous.

    Difficulty in climbing stairs
    NEG_FINDINGS

    , standing up and walking
    SYMPTOMS

 subsequently appeared, but rarely progressed to

    confinement to bed
    NEG_FINDINGS

.

    The forearms became mildly atrophic
    SYMPTOMS

, with

    decrease in grip strength
    SYMPTOMS

, but

    the small hand muscles were spared
    NEG_FINDINGS

. The

    EMG
    PARACLINICAL

 showed

    myopathic changes
    SYMPTOMS

 and

    nerve conduction was normal
    NEG_FINDINGS

.

    Serum creatine kinase activity was characteristically increased up to 100-fold
    BIOCHEMICAL

 in the early stages of the disease. It was also

    markedly increased
    BIOCHEMICAL

 in subjects in the preclinical stage and mildly in some

    heterozygotes
    GENETICS

.

    Muscle biopsies
    PARACLINICAL

 revealed

    myopathic changes with severe segmental necrosis accompanied by regeneration
    SYMPTOMS

. The changes were similar to those of

    Duchenne muscular dystrophy
    DIAGNOSIS

. An

    autopsied
    PARACLINICAL

 case,

    aged 68 years
    AGE

, showed

    generalized muscle abnormalities
    SYMPTOMS

    with a distal predominance
    SYMPTOMS

.

    The muscles in the lower legs, especially those of the calves, were severely affected
    SYMPTOMS

.

    No lesions were found in the brain, spinal cord or peripheral nerves
    NEG_FINDINGS

.


Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal insufficiency associated with Xp21 interstitial deletion.

We report an interstitial deletion in the short arm of the X chromosome in a 6-year-old boy with Duchenne muscular dystrophy, glycerol kinase deficiency, adrenal insufficiency, intermittent hypoglycemia, spasticity, psychomotor retardation, and growth delay. His mother also has this deletion in an X chromosome. From our findings, we propose that the human glycerol kinase locus and the human X-linked adrenal hypoplasia locus are in the Xp21 band.

We report an

    interstitial deletion in the short arm of the X chromosome
    GENETICS

 in a

    6-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

,

    glycerol kinase deficiency
    BIOCHEMICAL

,

    adrenal insufficiency
    BIOCHEMICAL

,

    intermittent hypoglycemia
    SYMPTOMS

,

    spasticity
    SYMPTOMS

,

    psychomotor retardation
    SYMPTOMS

, and

    growth delay
    SYMPTOMS

.

    His
    GENDER

    mother also has this deletion in an X chromosome
    FAMILY

. From our findings, we propose that the

    human glycerol kinase locus and the human X-linked adrenal hypoplasia locus are in the Xp21 band
    GENETICS

.

glycerol kinase deficiency
adrenal insufficiency

intermittent hypoglycemia
spasticity
psychomotor retardation
growth delay


[Heart arrest during general anesthesia in a child with unrecognized Duchenne's dystrophy].

A three-year old child was anaesthetized by halothane. Cardiac arrest occurred soon after the injection of suxamethonium. Signs of rhabdomyolysis associated with hyperkalemia were present. The diagnosis of Duchenne muscular dystrophy was obtained afterwards.

A

    three-year old
    AGE

    child
    AGE

 was

    anaesthetized by halothane
    MEDICATION

.

    Cardiac arrest
    SYMPTOMS

 occurred soon after the

    injection of suxamethonium
    MEDICATION

.

    Signs of rhabdomyolysis
    SYMPTOMS

 associated with

    hyperkalemia
    BIOCHEMICAL

 were present. The diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

 was obtained afterwards.

anaesthetized by halothane
injection of suxamethonium


Clinical features in a girl with Duchenne muscular dystrophy with an X-autosome translocation; (X;4)(p21;q26).

A female with Duchenne muscular dystrophy (DMD) and an X/4 translocation is reported. Her clinical signs, laboratory data and muscle pathology are compatible with those of typical DMD. She also has a ASD, type II, with some kind of cardiomyopathy. Detailed cytogenetic analyses by means of high resolution banding and R-banding techniques showed that the exchange point was located in band p21 of the X chromosome, suggesting the localization of the DMD gene within it. The clinical course of DMD in a female with an X/autosome translocation is variable, as in the case of heterozygous females, compared with that in male patients. The mild phenotype in female cases with an X/autosome translocation could be explained by the fact that in some cultured cells the normal X chromosomes replicate early and therefore may be active.

A

    female
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 and an

    X/4 translocation
    GENETICS

 is reported.

    Her
    GENDER

 clinical signs,

    laboratory data
    SYMPTOMS

 and

    muscle pathology
    SYMPTOMS

 are compatible with those of typical

    DMD
    DIAGNOSIS

.

    She
    GENDER

 also has a

    ASD, type II
    DIAGNOSIS

, with some kind of

    cardiomyopathy
    SYMPTOMS

.

    Detailed cytogenetic analyses
    PARACLINICAL

 by means of

    high resolution banding and R-banding techniques
    PARACLINICAL

 showed that

    the exchange point was located in band p21 of the X chromosome
    GENETICS

, suggesting the

    localization of the DMD gene within it
    GENETICS

. The clinical course of

    DMD
    DIAGNOSIS

 in a

    female
    GENDER

 with an

    X/autosome translocation
    GENETICS

 is variable, as in the case of

    heterozygous
    GENETICS

    females
    GENDER

, compared with that in

    male
    GENDER

 patients. The mild phenotype in

    female
    GENDER

 cases with an

    X/autosome translocation
    GENETICS

 could be explained by the fact that in some cultured cells the

    normal X chromosomes replicate early
    GENETICS

 and therefore may be active.

Duchenne muscular dystrophy (DMD)
DMD
ASD, type II
DMD

laboratory data
muscle pathology
cardiomyopathy


[Progressive muscular dystrophy of the Duchenne type].

A case of sudden death is reported that occurred as a result of Duchenne type progressive muscular dystrophy with extreme myogenic changes. These changes consisted of extensive muscular lipomatous transformation, typical of the advanced stage of the disease. The heart showed myocardial fibrosis, the respiratory system acute tracheobronchitis with early signs of bronchopneumonia. The pattern of distribution of the changes in the musculature is discussed with regard to the sudden death as well as to the possibility that medical malpractice may have occurred.

A case of

    sudden death
    SYMPTOMS

 is reported that occurred as a result of

    Duchenne type progressive muscular dystrophy
    DIAGNOSIS

 with

    extreme myogenic changes
    SYMPTOMS

. These changes consisted of

    extensive muscular lipomatous transformation
    SYMPTOMS

, typical of the advanced stage of the disease. The

    heart
    SYMPTOMS

 showed

    myocardial fibrosis
    SYMPTOMS

, the

    respiratory system acute tracheobronchitis
    SYMPTOMS

 with

    early signs of bronchopneumonia
    SYMPTOMS

. The pattern of distribution

    of the changes in the musculature
    SYMPTOMS

 is discussed with regard to the

    sudden death
    SYMPTOMS

 as well as to the possibility that medical malpractice may have occurred.


Progressive muscular dystrophy with congenital adrenal hypoplasia: an unusual autopsy case.

A 3 1/2-year-old child with progressive muscular dystrophy (PMD) and congenital adrenal hypoplasia (CAH) is described. Symptoms and signs of adrenocortical insufficiency appeared shortly after birth. Despite corticosteroid therapy, the muscular weakness and elevated CK level continued. A diagnosis of Duchenne muscular dystrophy was made on the basis of clinical signs and characteristic muscle biopsy. The affection of his older brother suggests an X-linked recessive inheritance. The autopsy revealed a very rare combination of cytomegalic type CAH and PMD. This combination suggests that a small deletion of X-chromosome might be responsible for the two disorders.

A

    3 1/2-year-old
    AGE

    child
    AGE

 with

    progressive muscular dystrophy (PMD)
    DIAGNOSIS

 and

    congenital adrenal hypoplasia (CAH)
    DIAGNOSIS

 is described.

    Symptoms and signs of adrenocortical insufficiency
    SYMPTOMS

 appeared

    shortly after birth
    AGE

.

    Despite corticosteroid therapy
    NEG_FINDINGS

, the

    muscular weakness
    SYMPTOMS

 and

    elevated CK level
    BIOCHEMICAL

 continued. A diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

 was made on the basis of clinical signs and

    characteristic muscle biopsy
    PARACLINICAL

.

    The affection of his older brother suggests an X-linked recessive inheritance
    FAMILY

. The

    autopsy
    PARACLINICAL

 revealed a very rare

    combination of cytomegalic type CAH and PMD
    DIAGNOSIS

. This combination suggests that a

    small deletion of X-chromosome
    GENETICS

 might be responsible for the two disorders.


Accidental death associated with motorized wheelchair use: a case report.

Motorized wheelchairs provide independence for individuals with a wide variety of severely disabling conditions. The benefits of powered mobility are widely appreciated. In this case report, one potential risk associated with motorized wheelchairs is illustrated by the accidental death of a young man with Duchenne type muscular dystrophy. Careful patient selection, anticipatory guidance and training should help minimize any risks.

    Motorized wheelchairs
    MEDICATION

 provide

    independence
    MEDICATION

 for individuals with a wide variety of severely disabling conditions. The benefits of

    powered mobility
    MEDICATION

 are widely appreciated. In this case report, one potential risk associated with

    motorized wheelchairs
    MEDICATION

 is illustrated by the

    accidental death
    SYMPTOMS

 of a

    young
    AGE

    man
    GENDER

 with

    Duchenne type muscular dystrophy
    DIAGNOSIS

. Careful patient selection, anticipatory guidance and training should help minimize any risks.

Motorized wheelchairs
independence
powered mobility
motorized wheelchairs


Enzymatic analysis of individual posterior root ganglion cells in olivopontocerebellar atrophy, amyotrophic lateral sclerosis and Duchenne muscular dystrophy.

Four enzyme activities related to glucose metabolism, i.e. those of glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49), lactic dehydrogenase (LDH; EC 1.1.1.27), pyruvate dehydrogenase complex (PDC) and citrate synthase (CS; EC 4.1.3.7) were estimated in posterior root ganglion cells (PRGCs) of the spinal cord in patients suffering from olivopontocerebellar atrophy (OPCA), amyotrophic lateral sclerosis (ALS), and Duchenne muscular dystrophy (DMD) by means of the NAD, NADP and CoA cycling methods. In ALS and DMD, the enzyme activities examined were within normal ranges. In OPCA, PDC activity was significantly reduced and LDH activity tended to be lower than that in controls.

    Four enzyme activities related to glucose metabolism
    BIOCHEMICAL

, i.e.

    those of glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49), lactic dehydrogenase (LDH; EC 1.1.1.27), pyruvate dehydrogenase complex (PDC) and citrate synthase (CS; EC 4.1.3.7)
    BIOCHEMICAL

 were estimated in

    posterior root ganglion cells (PRGCs) of the spinal cord
    MICROSCOPIC

 in patients suffering from

    olivopontocerebellar atrophy (OPCA)
    DIAGNOSIS

,

    amyotrophic lateral sclerosis (ALS)
    DIAGNOSIS

, and

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 by means of the

    NAD, NADP and CoA cycling methods
    PARACLINICAL

. In

    ALS
    DIAGNOSIS

 and

    DMD
    DIAGNOSIS

,

    the enzyme activities examined were within normal ranges
    NEG_FINDINGS

. In

    OPCA
    DIAGNOSIS

,

    PDC activity was significantly reduced
    BIOCHEMICAL

 and

    LDH activity tended to be lower than that
    BIOCHEMICAL

 in controls.

olivopontocerebellar atrophy (OPCA)
amyotrophic lateral sclerosis (ALS)
Duchenne muscular dystrophy (DMD)
ALS
DMD
OPCA


Duchenne-like muscular dystrophy in two sisters with normal karyotypes: evidence for autosomal recessive inheritance.

Two sisters, products of a consanguineous marriage (with a total of 12 children) showed muscle weakness at ages 7 and 6 yrs, respectively. The symptoms progressed rapidly and the patients were confined to wheelchairs at ages of 12 and 11 yrs, respectively. They had mild facial weakness and pseudohypertrophy of the calves, but neither cardiomyopathy nor mental retardation. Serum CK activities exceeded upper normal limit by 70 to 85-fold. Muscle biopsies were compatible with muscular dystrophy. Both girls had a normal karyotype. The healthy mother had mild CK elevations in two out of three occasions, but the muscle biopsy was normal. Three out of the six unaffected sibs had mild CK elevations. The findings support the concept of severe progressive muscular dystrophy with autosomal recessive inheritance. The condition is clinically indistinguishable from Duchenne muscular dystrophy.

    Two sisters, products of a consanguineous marriage (with a total of 12 children) showed muscle weakness
    FAMILY

 at

    ages 7 and 6 yrs
    AGE

, respectively. The symptoms progressed rapidly and the patients were

    confined to wheelchairs
    MEDICATION

 at

    ages of 12 and 11 yrs
    AGE

, respectively. They had

    mild facial weakness
    SYMPTOMS

 and

    pseudohypertrophy of the calves
    SYMPTOMS

, but

    neither cardiomyopathy nor mental retardation
    NEG_FINDINGS

.

    Serum CK activities exceeded upper normal limit by 70 to 85-fold
    BIOCHEMICAL

.

    Muscle biopsies
    PARACLINICAL

 were compatible with

    muscular dystrophy
    DIAGNOSIS

. Both

    girls
    GENDER

 had a

    normal karyotype
    NEG_FINDINGS

. The

    healthy mother had mild CK elevations
    FAMILY

 in two out of three occasions, but

    the muscle biopsy was normal
    NEG_FINDINGS

.

    Three out of the six unaffected sibs had mild CK elevations
    FAMILY

. The findings support the concept of

    severe progressive muscular dystrophy
    DIAGNOSIS

 with

    autosomal recessive inheritance
    GENETICS

. The condition is clinically indistinguishable from

    Duchenne muscular dystrophy
    DIAGNOSIS

.

mild facial weakness
pseudohypertrophy of the calves

muscular dystrophy
severe progressive muscular dystrophy
Duchenne muscular dystrophy


The psychosocial impact of a progressive physical handicap and terminal illness (Duchenne muscular dystrophy) on adolescents and their families.

This paper reports in narrative style on a sample of 13-16-year-old Duchenne muscular dystrophy adolescents in a residential setting in the UK. The terminally ill dystrophic boys' physical handicaps were noticed at about five years of age. In-depth interviews were conducted with parents, while projective assessment and psychodrama were used with the boys. Findings for this paper draw heavily on family interviews. Not surprisingly, the Duchenne boys evinced significant isolation from the mainstream of normal culture. The parents of the terminal group showed marked preoccupation with their sons, great stress and diminished expression of enjoyment. The Duchenne adolescents raised the issue of handicap surprisingly often with their parents, suggesting their great need to acknowledge their disease with parents. Their parents, however, evinced marked difficulty in responding to death issues with the boys - a reaction which leaves the boys alone and the parents guilty. These observations on the family are discussed in the context of a family identification process.

This paper reports in narrative style on a sample of

    13-16-year-old
    AGE

    Duchenne muscular dystrophy
    DIAGNOSIS

    adolescents
    AGE

 in a residential setting in the

    UK
    ETHNICITY

. The

    terminally ill dystrophic boys
    DIAGNOSIS

'

    physical handicaps
    SYMPTOMS

 were noticed at

    about five years of age
    AGE

.

    In-depth interviews
    PARACLINICAL

 were conducted with

    parents
    PARACLINICAL

, while

    projective assessment and psychodrama
    PARACLINICAL

 were used with the

    boys
    GENDER

. Findings for this paper draw heavily on

    family interviews
    PARACLINICAL

. Not surprisingly, the

    Duchenne
    DIAGNOSIS

    boys
    GENDER

 evinced

    significant isolation from the mainstream of normal culture
    SYMPTOMS

. The parents of the terminal group showed

    marked preoccupation with their sons
    SYMPTOMS

,

    great stress
    SYMPTOMS

 and

    diminished expression of enjoyment
    SYMPTOMS

. The

    Duchenne
    DIAGNOSIS

    adolescents
    GENDER

 raised the issue of

    handicap
    SYMPTOMS

 surprisingly often with their parents, suggesting their great need to acknowledge their disease with parents. Their parents, however, evinced

    marked difficulty in responding to death issues
    SYMPTOMS

 with the

    boys
    GENDER

 - a reaction which leaves the

    boys
    GENDER

 alone and the parents guilty. These observations on the family are discussed in the context of a family identification process.

Duchenne muscular dystrophy
terminally ill dystrophic boys
Duchenne
Duchenne


Duchenne muscular dystrophy: a case with prolonged survival.

We report the case of a patient with confirmed Duchenne muscular dystrophy who lived a useful and improved life until age 34. He was first seen in our Muscular Dystrophy Clinic when he was 14; at that time he was functionally quadriplegic and required assistance for all activities of daily living. At age 17, ventilatory insufficiency developed and the patient was provided with a positive pressure device (mouthpiece) to augment his ventilation. A year later he learned the technique of glossopharyngeal breathing. After surviving acute pneumonia at age 24, he became a licensed real estate salesman and was married at age 29 to his attendant (the marriage ended in divorce). He eventually enrolled as a student at Ohio State University, lived on campus, and moved about in a powered wheelchair. He died an accidental death by drowning at age 34 when his wheelchair veered suddenly into a pond eight feet deep.

We report the case of a patient with confirmed

    Duchenne muscular dystrophy
    DIAGNOSIS

 who lived a useful and improved life until

    age 34
    AGE

.

    He
    GENDER

 was first seen in our

    Muscular Dystrophy
    DIAGNOSIS

 Clinic when

    he was 14
    AGE

; at that time

    he
    GENDER

 was

    functionally quadriplegic
    SYMPTOMS

 and

    required assistance for all activities of daily living
    MEDICATION

. At

    age 17
    AGE

,

    ventilatory insufficiency
    SYMPTOMS

 developed and the patient was

    provided with a positive pressure device (mouthpiece) to augment his ventilation
    MEDICATION

. A year later he learned the

    technique of glossopharyngeal breathing
    MEDICATION

. After surviving

    acute pneumonia
    DIAGNOSIS

 at

    age 24
    AGE

,

    he
    GENDER

 became a

    licensed real estate salesman
    MEDICATION

 and was

    married
    MEDICATION

 at

    age 29 to his attendant (the marriage ended in divorce)
    AGE

.

    He
    GENDER

 eventually

    enrolled as a student at Ohio State University
    MEDICATION

,

    lived on campus
    MEDICATION

, and

    moved about in a powered wheelchair
    MEDICATION

.

    He
    GENDER

    died
    SYMPTOMS

 an

    accidental death by drowning
    SYMPTOMS

 at

    age 34
    AGE

 when his

    wheelchair veered suddenly into a pond eight feet deep
    MEDICATION

.

Duchenne muscular dystrophy
Muscular Dystrophy
acute pneumonia

functionally quadriplegic
ventilatory insufficiency
died
accidental death by drowning


Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome.

We are reporting a male patient who suffered from chronic granulomatous disease associated with cytochrome b-245 deficiency and McLeod red cell phenotype, Duchenne muscular dystrophy, and retinitis pigmentosa. On cytogenetic analysis, he seemed to have a very subtle interstitial deletion of part of band Xp21. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome, somatic cell and molecular studies were carried out. In somatic cell hybrids, the deleted X chromosome was isolated on a Chinese hamster background. Southern blot analysis with 20 single-copy probes, that had been mapped to the X short arm, led to the discovery of one (probe 754) that is missing from this patient's X chromosome and also from his total DNA. This proves that he, indeed, has a deletion rather than a balanced insertion. The results provide cytological mapping information for the X-linked phenotypes present in this patient. Furthermore, probe 754 recognizes a restriction fragment length polymorphism of high frequency that makes it the most powerful probe currently available for linkage studies with X-linked muscular dystrophy.

We are reporting a

    male
    GENDER

 patient who suffered from

    chronic granulomatous disease
    DIAGNOSIS

 associated with

    cytochrome b-245 deficiency
    BIOCHEMICAL

 and

    McLeod red cell phenotype
    BIOCHEMICAL

,

    Duchenne muscular dystrophy
    DIAGNOSIS

, and

    retinitis pigmentosa
    DIAGNOSIS

. On

    cytogenetic analysis
    PARACLINICAL

,

    he
    GENDER

 seemed to have a

    very subtle interstitial deletion of part of band Xp21
    GENETICS

. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome,

    somatic cell and molecular studies
    PARACLINICAL

 were carried out. In

    somatic cell hybrids
    MICROSCOPIC

, the

    deleted X chromosome
    GENETICS

 was isolated on a Chinese hamster background.

    Southern blot analysis with 20 single-copy probes
    PARACLINICAL

, that had been mapped

    to the X short arm
    PARACLINICAL

, led to the discovery of

    one (probe 754) that is missing from this patient's X chromosome and also from his total DNA
    GENETICS

. This proves that

    he
    GENDER

, indeed, has a

    deletion rather than a balanced insertion
    GENETICS

. The results provide cytological mapping information for the

    X-linked phenotypes
    GENETICS

 present in this patient. Furthermore, probe 754 recognizes a

    restriction fragment length polymorphism of high frequency
    GENETICS

 that makes it the most powerful probe currently available for linkage studies with

    X-linked muscular dystrophy
    DIAGNOSIS

.

chronic granulomatous disease
Duchenne muscular dystrophy
retinitis pigmentosa
X-linked muscular dystrophy

cytochrome b-245 deficiency
McLeod red cell phenotype


Computed tomographic findings in manifesting carriers of Duchenne muscular dystrophy.

Clinical and computed tomographic (CT) findings in 3 manifesting carriers of Duchenne muscular dystrophy are reported. CT proved to be an important adjunct to the clinical examination: in all our 3 cases a decrease in density was found in various non-paretic muscles.

Clinical and

    computed tomographic (CT)
    PARACLINICAL

 findings in 3 manifesting carriers of

    Duchenne muscular dystrophy
    DIAGNOSIS

 are reported.

    CT
    PARACLINICAL

 proved to be an important adjunct to the

    clinical examination
    PARACLINICAL

: in all our 3 cases a

    decrease in density was found in various non-paretic muscles
    SYMPTOMS

.


Lipid composition of the cerebral gray and white matter in a case with Fukuyama type congenital muscular dystrophy.

When compared with an age-matched normal control and a Duchenne muscular dystrophy (DMD) case, the patient with FCMD had an unusual ganglioside pattern in the cerebral gray matter. The total level of lipid-bound sialic acid in the cerebral gray matter was also slightly decreased. However, other lipid compositions of the cerebral gray and white matter were normal compared with those in the control case.

When compared with an age-matched normal control and a

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 case, the patient with

    FCMD
    DIAGNOSIS

 had an

    unusual ganglioside pattern in the cerebral gray matter
    MICROSCOPIC

. The

    total level of lipid-bound sialic acid in the cerebral gray matter was also slightly decreased
    MICROSCOPIC

. However,

    other lipid compositions of the cerebral gray and white matter were normal
    NEG_FINDINGS

 compared with those in the control case.


High-resolution banding study of an X/4 translocation in a female with Duchenne muscular dystrophy.

A rare female case of Duchenne muscular dystrophy with an X/4 translocation was found. Detailed cytogenetic analyses by R-banding and high-resolution G-banding techniques revealed that the exchange point involved in the translocation was at the p21.1 band on the X chromosome.

A rare

    female
    GENDER

 case of

    Duchenne muscular dystrophy
    DIAGNOSIS

 with an

    X/4 translocation
    GENETICS

 was found.

    Detailed cytogenetic analyses
    PARACLINICAL

 by

    R-banding and high-resolution G-banding techniques
    PARACLINICAL

 revealed that

    the exchange point involved in the translocation was at the p21.1 band on the X chromosome
    GENETICS

.


[Treatment of Duchenne's myopathy with early physiotherapy. Critical analysis].

The efficiency of a therapeutic modality in Duchenne Muscular Dystrophy (DMD) is difficult to judge. The usual criterion used is the time period between the beginning of walking and its loss. Thirty-five patients treated with early intensive physiotherapy were compared with 28 untreated ones. On average, the prolongation of walking in the treated group was 8 months. However, average age of death was 18 years 8 months in treated patients and 20 years 2 months in untreated patients. In order to judge the benefits of a treatment it is absolutely essential to consider the whole of the evolution of the disease, without omitting the wheelchair bound stage when the most severe complications occur.

The efficiency of a therapeutic modality in

    Duchenne Muscular Dystrophy (DMD)
    DIAGNOSIS

 is difficult to judge. The usual criterion used is the time period between the

    beginning of walking and its loss
    SYMPTOMS

. Thirty-five patients treated with

    early intensive physiotherapy
    MEDICATION

 were compared with 28 untreated ones. On average, the

    prolongation of walking
    SYMPTOMS

 in the treated group was

    8 months
    AGE

. However,

    average age of death was 18 years 8 months
    AGE

 in treated patients and

    20 years 2 months
    AGE

 in untreated patients. In order to judge the benefits of a treatment it is absolutely essential to consider the whole of the evolution of the disease, without omitting the

    wheelchair bound
    MEDICATION

 stage when the most severe complications occur.

beginning of walking and its loss
prolongation of walking

early intensive physiotherapy
wheelchair bound


Succinylcholine-induced cardiac arrest in unsuspected Duchenne muscular dystrophy.

A case history is presented of a three-year-old boy with unsuspected Duchenne muscular dystrophy, who suffered a cardiac arrest following the administration of a single dose of succinylcholine during a halothane anaesthetic. The arrest was associated with lack of fasciculations, muscle rigidity, hyperkalemia, myoglobinuria, and massive elevation of serum creatine phosphokinase. Asystole was prolonged and refractory to treatment, although cardiac activity was eventually restored. The possible cause of the circulatory collapse is discussed and reports of similar cases reviewed. Neither succinylcholine nor halothane should be employed in cases with known or suspected Duchenne muscular dystrophy.

A case history is presented of a

    three-year-old
    AGE

    boy
    GENDER

 with

    unsuspected Duchenne muscular dystrophy
    NEG_FINDINGS

, who suffered a

    cardiac arrest
    SYMPTOMS

 following the

    administration of a single dose of succinylcholine during a halothane anaesthetic
    MEDICATION

. The

    arrest
    SYMPTOMS

 was associated with

    lack of fasciculations
    SYMPTOMS

,

    muscle rigidity
    SYMPTOMS

,

    hyperkalemia
    BIOCHEMICAL

,

    myoglobinuria
    BIOCHEMICAL

, and

    massive elevation of serum creatine phosphokinase
    BIOCHEMICAL

.

    Asystole was prolonged
    SYMPTOMS

 and

    refractory to treatment
    NEG_FINDINGS

, although

    cardiac activity was eventually restored
    SYMPTOMS

. The possible cause of the

    circulatory collapse
    SYMPTOMS

 is discussed and reports of similar cases reviewed.

    Neither succinylcholine
    MEDICATION

 nor

    halothane
    MEDICATION

 should be employed in cases with known or suspected

    Duchenne muscular dystrophy
    DIAGNOSIS

.

unsuspected Duchenne muscular dystrophy
refractory to treatment


Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome.

A young female was diagnosed as having X-linked muscular dystrophy of the Duchenne type. Chromosome studies, including trypsin-Giemsa banding, Quinacrine fluorescence, and nucleolus organizer region (NOR) silver staining revealed an X-autosome reciprocal translocation t(X;21) (p21;p12). Utilizing both [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique, lymphocytes and fibroblasts were found to show a preferential inactivation of the normal X suggesting the presence of a single mutant gene on the translocated X. This patient is one of seven reported cases of an X-linked muscular dystrophy associated with an X-autosome translocation. In all seven cases the exchange point in the X chromosome is in band p21 at or near the site of the Duchenne gene.

A

    young
    AGE

    female
    GENDER

 was diagnosed as having

    X-linked muscular dystrophy of the Duchenne type
    DIAGNOSIS

.

    Chromosome studies
    PARACLINICAL

, including

    trypsin-Giemsa banding
    PARACLINICAL

,

    Quinacrine fluorescence
    PARACLINICAL

, and

    nucleolus organizer region (NOR) silver staining
    PARACLINICAL

 revealed an

    X-autosome reciprocal translocation t(X;21) (p21;p12)
    GENETICS

. Utilizing both

    [3H] thymidine autoradiography and the BrdU-Hoechst 33258-Giemsa technique
    PARACLINICAL

,

    lymphocytes and fibroblasts
    MICROSCOPIC

 were found to show a

    preferential inactivation of the normal X
    GENETICS

 suggesting the presence of a single mutant gene on the translocated X. This patient is one of seven reported cases of an

    X-linked muscular dystrophy
    DIAGNOSIS

 associated with an

    X-autosome translocation
    GENETICS

. In all seven cases the

    exchange point in the X chromosome is in band p21 at or near the site of the Duchenne gene
    GENETICS

.


Regenerated muscle fibers in Duchenne muscular dystrophy: a serial section study.

Muscle fibers from two boys with Duchenne muscular dystrophy and one normal boy were, for 6 mm, traced in serial sections. In normal muscle, we saw no branching or terminating fibers, and fiber diameters varied in different levels by +/- 5%. Dystrophic muscles showed signs of regeneration after segmental necrosis: multiple branchings, caliber variations, and short noninnervated fibers. In rats, muscle fibers regenerate without innervation but eventually they are replaced by fat cells. In Duchenne muscles, some regenerates lack innervation and possibly vanish as well; this may explain why regeneration finally fails.

    Muscle fibers
    PARACLINICAL

 from two

    boys
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 and one normal

    boy
    GENDER

 were,

    for 6 mm
    PARACLINICAL

,

    traced in serial sections
    PARACLINICAL

. In

    normal muscle
    NEG_FINDINGS

, we saw

    no branching or terminating fibers
    NEG_FINDINGS

, and

    fiber diameters varied in different levels by +/- 5%
    SYMPTOMS

.

    Dystrophic muscles
    DIAGNOSIS

 showed

    signs of regeneration
    SYMPTOMS

 after

    segmental necrosis
    SYMPTOMS

:

    multiple branchings
    SYMPTOMS

,

    caliber variations
    SYMPTOMS

, and

    short noninnervated fibers
    SYMPTOMS

. In rats,

    muscle fibers regenerate without innervation
    MICROSCOPIC

 but

    eventually they are replaced by fat cells
    MICROSCOPIC

. In

    Duchenne muscles
    DIAGNOSIS

,

    some regenerates lack innervation and possibly vanish as well
    SYMPTOMS

; this may explain why

    regeneration finally fails
    SYMPTOMS

.

Duchenne muscular dystrophy
Dystrophic muscles
Duchenne muscles

normal muscle
no branching or terminating fibers


X-linked Duchenne muscular dystrophy in an unusual family with manifesting carriers.

We report a unique case of a 46-year-old female who had signs of Duchenne-like muscular dystrophy on clinical, electromyographic, and laboratory investigation. A brother, sister, maternal uncle, and her own son also had Duchenne type muscular dystrophy. Karyotype analysis in the proband showed both the X chromosomes to be morphologically normal. We discuss different hypothetical mechanisms to account for the family pedigree.

We report a unique case of a

    46-year-old
    AGE

    female
    GENDER

 who had

    signs of Duchenne-like muscular dystrophy
    SYMPTOMS

 on

    clinical, electromyographic, and laboratory investigation
    PARACLINICAL

. A

    brother, sister, maternal uncle, and her own son also had Duchenne type muscular dystrophy
    FAMILY

.

    Karyotype analysis
    PARACLINICAL

 in the proband showed

    both the X chromosomes to be morphologically normal
    NEG_FINDINGS

. We discuss different hypothetical mechanisms to account for the family pedigree.


Diagnostic application of first trimester trophoblast sampling in 100 pregnancies.

The results of the diagnostic application of first trimester trophoblast sampling in 100 pregnancies are reported in detail. Further improvement of the method for routine, direct chromosome analysis resulted in a technique which proved to be fast, simple, and efficient. We found that short-term incubation of villi permits the application of many experimental methods, such as visualization of sister chromatid exchanges and bromodeoxyuridine (BrdU) incorporation. Fetal karyotyping was successful in each of the 96 pregnancies in which fetal material was obtained from a total of 98 fetuses. There were 42 males and 56 females, and an abnormal chromosome constitution was found in 12 cases. Two trisomic fetuses were found among the eight pregnancies at risk for Duchenne muscular dystrophy, and this indicates that fetal sexing (which is achieved with our method in two hours) should not be performed without chromosome visualization. The results indicate a risk of 8% of an abnormal fetus for mothers aged 35 years or more, while the risk of failure of sampling and of spontaneous abortion after villi sampling were 4 and 6%, respectively. Enzyme determinations were performed in three pregnancies at risk for gangliosidosis GM1, Niemann-Pick disease, and Hurler syndrome. In this last case inconsistency between the results of the assay of iduronidase on chorionic villi and amniotic fluid cells was found. This unexplained error indicates the need for extensive characterisation in chorionic villi of the series of enzymes involved in metabolic diseases.

The results of the diagnostic application of

    first trimester trophoblast sampling
    PARACLINICAL

 in 100

    pregnancies
    DIAGNOSIS

 are reported in detail. Further improvement of the method for routine,

    direct chromosome analysis
    PARACLINICAL

 resulted in a technique which proved to be fast, simple, and efficient. We found that

    short-term incubation of villi
    PARACLINICAL

 permits the application of many experimental methods, such as

    visualization of sister chromatid exchanges
    PARACLINICAL

 and

    bromodeoxyuridine (BrdU) incorporation
    PARACLINICAL

.

    Fetal karyotyping
    PARACLINICAL

 was successful in each of the 96 pregnancies in which fetal material was obtained from a total of 98 fetuses. There were 42

    males
    GENDER

 and 56

    females
    GENDER

, and an

    abnormal chromosome constitution
    SYMPTOMS

 was found in 12 cases. Two

    trisomic fetuses
    GENETICS

 were found among the eight

    pregnancies
    DIAGNOSIS

 at risk for

    Duchenne muscular dystrophy
    DIAGNOSIS

, and this indicates that

    fetal sexing
    PARACLINICAL

 (which is achieved with our method in two hours) should not be performed without

    chromosome visualization
    PARACLINICAL

. The results indicate a risk of 8% of an

    abnormal fetus
    SYMPTOMS

 for

    mothers
    AGE

    aged 35 years or more
    AGE

, while the risk of

    failure of sampling
    NEG_FINDINGS

 and of

    spontaneous abortion
    SYMPTOMS

 after

    villi sampling
    MEDICATION

 were 4 and 6%, respectively.

    Enzyme determinations
    PARACLINICAL

 were performed in three

    pregnancies
    DIAGNOSIS

 at risk for

    gangliosidosis GM1
    DIAGNOSIS

,

    Niemann-Pick disease
    DIAGNOSIS

, and

    Hurler syndrome
    DIAGNOSIS

. In this last case

    inconsistency between the results of the assay of iduronidase on chorionic villi and amniotic fluid cells
    SYMPTOMS

 was found. This unexplained error indicates the need for extensive characterisation in

    chorionic villi
    PARACLINICAL

 of the series of enzymes involved in

    metabolic diseases
    DIAGNOSIS

.

pregnancies
pregnancies
Duchenne muscular dystrophy
pregnancies
gangliosidosis GM1
Niemann-Pick disease
Hurler syndrome
metabolic diseases


Turner's syndrome and Duchenne muscular dystrophy in a girl with an X; autosome translocation.

A balanced de novo (X;9) translocation was observed in a patient with progressive muscular dystrophy of Duchenne's type (DMD), Turner's syndrome, epilepsy and mental retardation. The involvement of the paternal X is suggested. The assignment of the gene locus for DMD is confirmed on Xp21.

A

    balanced de novo (X;9) translocation
    GENETICS

 was observed in a patient with

    progressive muscular dystrophy of Duchenne's type (DMD)
    DIAGNOSIS

,

    Turner's syndrome
    DIAGNOSIS

,

    epilepsy
    SYMPTOMS

 and

    mental retardation
    SYMPTOMS

. The

    involvement of the paternal X
    GENETICS

 is suggested. The assignment of the

    gene locus for DMD
    GENETICS

 is confirmed on

    Xp21.
    GENETICS

balanced de novo (X;9) translocation
involvement of the paternal X
gene locus for DMD
Xp21.


Further evidence for Xp21 location of Duchenne muscular dystrophy (DMD) locus: X;9 translocation in a female with DMD.

Females who fully manifest Duchenne muscular dystrophy (DMD), an X linked disorder, are extremely rare. Cytogenetic studies are indicated in such females to rule out an X chromosome abnormality, which could render a female hemizygous for X linked genes. At present there are six reports describing females with Duchenne muscular dystrophy and an X; autosome translocation. Although each of these six rearrangements involves a different autosome, (chromosomes 11, 21, 1, 3, 5, and 6) they have in common a breakpoint at Xp21. We report here our observations of a further female with DMD who carries a de novo translocation between Xp and 9p. The breakpoint in our patient is also located at Xp21, adding evidence for the assignment of this band as the site of the DMD gene.

    Females
    GENDER

 who fully manifest

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, an

    X linked disorder
    GENETICS

, are extremely rare.

    Cytogenetic studies
    PARACLINICAL

 are indicated in such

    females
    GENDER

 to rule out an

    X chromosome abnormality
    GENETICS

, which could render a

    female
    GENDER

    hemizygous for X linked genes
    GENETICS

. At present there are six reports describing

    females
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 and an

    X; autosome translocation
    GENETICS

. Although each of these six

    rearrangements involves a different autosome, (chromosomes 11, 21, 1, 3, 5, and 6)
    GENETICS

 they have in common a

    breakpoint at Xp21
    GENETICS

. We report here our observations of a further

    female
    GENDER

 with

    DMD
    DIAGNOSIS

 who carries a

    de novo translocation between Xp and 9p
    GENETICS

. The breakpoint in our patient

    is also located at Xp21
    GENETICS

, adding evidence for the assignment of this band as the site of the

    DMD gene
    GENETICS

.

Duchenne muscular dystrophy (DMD)
Duchenne muscular dystrophy
DMD


Congenital adrenal hypoplasia, progressive muscular dystrophy, and severe mental retardation, in association with glycerol kinase deficiency, in male sibs.

A family is described with three male sibs suffering from congenital adrenal hypoplasia (CAH). In the two surviving brothers the disease is clinically further characterized by a Duchenne type muscular dystrophy, growth failure and severe mental retardation. Laboratory investigations revealed deficient activities of gonadotrophin and glycerol kinase. The clinical, biochemical and genetic findings in ths exceptional family are reported and discussed.

A

    family
    FAMILY

 is described

    with three male sibs suffering from congenital adrenal hypoplasia (CAH)
    FAMILY

. In the two surviving

    brothers
    GENDER

 the disease is clinically further characterized by a

    Duchenne type muscular dystrophy
    DIAGNOSIS

,

    growth failure
    SYMPTOMS

 and

    severe mental retardation
    SYMPTOMS

.

    Laboratory investigations
    PARACLINICAL

 revealed

    deficient activities of gonadotrophin and glycerol kinase
    BIOCHEMICAL

. The clinical, biochemical and genetic findings in ths exceptional family are reported and discussed.

growth failure
severe mental retardation


Reinnervation in Duchenne muscular dystrophy.

Motor neuron abnormalities have been implicated in the pathogenesis of Duchenne muscular dystrophy. Evidence concerning the effect of injury on motor neurons of human Duchenne muscular dystrophy (DMD) is lacking. We report a DMD patient having, in addition, an obstetric paresis on his left arm. EMG and muscle histochemistry showed signs of reinnervation superimposed on myopathy in his left arm. This suggests that sprouting is preserved in DMD motor neurons and that muscle fibers retain the capability of accepting reinnervation.

    Motor neuron abnormalities
    SYMPTOMS

 have been implicated in the pathogenesis of

    Duchenne muscular dystrophy
    DIAGNOSIS

. Evidence concerning the effect of

    injury
    SYMPTOMS

 on motor neurons of human

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is lacking. We report a

    DMD
    DIAGNOSIS

 patient having, in addition, an

    obstetric paresis on his left arm
    SYMPTOMS

.

    EMG and muscle histochemistry
    PARACLINICAL

 showed

    signs of reinnervation superimposed on myopathy in his left arm
    SYMPTOMS

. This suggests that

    sprouting is preserved in DMD motor neurons
    SYMPTOMS

 and that

    muscle fibers retain the capability of accepting reinnervation
    SYMPTOMS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD)
DMD


Anaesthesia induced rhabdomyolysis--a case report.

Anaesthesia-induced rhabdomyolysis (AIR) is a rare but serious complication of general anaesthesia. We report the occurrence of this event in a previously healthy three-year-old male, with a strongly positive family history of Duchenne muscular dystrophy. Following an uneventful anaesthetic, which included succinylcholine, myoglobinuria developed and led to renal failure which fortunately reversed with conservative treatment. Based on review of reports of similar cases, it is clear that succinylcholine should be avoided in paediatric patients with known myopathy or at high risk for latent myopathy.

    Anaesthesia-induced rhabdomyolysis (AIR)
    DIAGNOSIS

 is a rare but serious complication of

    general anaesthesia
    MEDICATION

. We report the occurrence of this event in a previously healthy

    three-year-old
    AGE

    male
    GENDER

, with a

    strongly positive family history of Duchenne muscular dystrophy
    FAMILY

. Following an

    uneventful anaesthetic, which included succinylcholine
    MEDICATION

,

    myoglobinuria
    BIOCHEMICAL

 developed and led to

    renal failure
    SYMPTOMS

 which fortunately reversed with

    conservative treatment
    MEDICATION

. Based on review of reports of similar cases, it is clear that

    succinylcholine
    MEDICATION

 should be avoided in

    paediatric
    AGE

 patients with known

    myopathy
    DIAGNOSIS

 or at high risk for

    latent myopathy
    DIAGNOSIS

.


[Lipid storage myopathy--a contribution to the problem of the differential diagnosis of muscle dystrophy (Duchenne)].

A case of a lipid myopathy in a 12-year-old boy is reported. The clinical picture was like a muscle-dystrophy (Duchenne) The histochemical investigations demonstrated the lipidmyopathy combined with a neurogenic atrophy.

A case of a

    lipid myopathy
    DIAGNOSIS

 in a

    12-year-old
    AGE

    boy
    GENDER

 is reported. The clinical picture was like a

    muscle-dystrophy (Duchenne)
    DIAGNOSIS

 The

    histochemical investigations
    PARACLINICAL

 demonstrated the

    lipidmyopathy
    DIAGNOSIS

 combined with a

    neurogenic atrophy
    SYMPTOMS

.

lipid myopathy
muscle-dystrophy (Duchenne)
lipidmyopathy


[Unusual peracute cardiac death cases].

The causes for peracute cardiac death often stem from dysfunction of action-monitoring within the conduction system. By different basic diseases of the heart-partially ischemic circulatory, partially biochemical-biophysical, rarely musculary disorders dominate. This is demonstrated at four cases of death accompanied by rare findings: (1) Localised stenosing coronary arteriosclerosis and -thrombosis at a 32-year-old woman; (2) anatomically corrected transposition of the large vessels; (3) generalized progressive muscular dystrophy (Morbus Duchenne); (4) chronical shrinkage of both kidneys and overdosed electrolyte supply.

The causes for

    peracute cardiac death
    SYMPTOMS

 often stem from

    dysfunction of action-monitoring within the conduction system
    SYMPTOMS

. By different

    basic diseases of the heart
    DIAGNOSIS

-

    partially ischemic circulatory
    SYMPTOMS

,

    partially biochemical-biophysical
    SYMPTOMS

, rarely

    musculary disorders
    DIAGNOSIS

 dominate. This is demonstrated at four cases of

    death
    SYMPTOMS

 accompanied by rare findings: (1)

    Localised stenosing coronary arteriosclerosis and -thrombosis
    SYMPTOMS

 at a

    32-year-old
    AGE

    woman
    GENDER

; (2)

    anatomically corrected transposition of the large vessels
    MEDICATION

; (3)

    generalized progressive muscular dystrophy (Morbus Duchenne)
    DIAGNOSIS

; (4)

    chronical shrinkage of both kidneys
    SYMPTOMS

 and

    overdosed electrolyte supply
    BIOCHEMICAL

.


An unusual cytoplasmic organelle of the perineurium in a case of Duchenne muscular dystrophy.

An unusual cytoplasmic organelle was found in the perineurial sheath of intramuscular nerves in a case of Duchenne muscular dystrophy. It was composed of alternating layers of ribosomes and fibrillar material helically wound around a core of cytoplasm. Comparable organelles have been described in leukemic and other neoplastic cells as well as in the developing cutaneous sensory corpuscle of Grandry.

    An unusual cytoplasmic organelle was found in the perineurial sheath of intramuscular nerves
    MICROSCOPIC

 in a case of

    Duchenne muscular dystrophy
    DIAGNOSIS

. It was

    composed of alternating layers of ribosomes and fibrillar material helically wound around a core of cytoplasm
    MICROSCOPIC

.

    Comparable organelles
    MICROSCOPIC

 have been described

    in leukemic and other neoplastic cells
    MICROSCOPIC

 as well as

    in the developing cutaneous sensory corpuscle of Grandry
    MICROSCOPIC

.


Cardiac manifestations of Becker-type muscular dystrophy.

The electro-, phonomechano- and echocardiographic manifestations observed in a family with documented X-linked Becker-type muscular dystrophy (BMD) are described. Important myocardial dystrophic lesions may occur in young patients with BMD. They are associated with typical electrocardiological findings which were described as a distinctive pattern in Duchenne-type muscular dystrophy. Myocardial involvement is seldom observed in heterozygotes for BMD.

The

    electro-, phonomechano- and echocardiographic
    PARACLINICAL

 manifestations observed in a

    family with documented X-linked Becker-type muscular dystrophy (BMD)
    FAMILY

 are described.

    Important myocardial dystrophic lesions
    SYMPTOMS

 may occur in

    young
    AGE

 patients with

    BMD
    DIAGNOSIS

. They are associated with

    typical electrocardiological findings
    SYMPTOMS

 which were described as a distinctive pattern in

    Duchenne-type muscular dystrophy
    DIAGNOSIS

.

    Myocardial involvement
    SYMPTOMS

 is seldom observed in

    heterozygotes for BMD
    GENETICS

.

Important myocardial dystrophic lesions
typical electrocardiological findings
Myocardial involvement


[Role and indications for surgery in Duchenne de Boulogne muscular dystrophy with rapid development].

One hundred and fifteen children suffering from muscular dystrophy had been treated surgically during the previous 12 years. The aim of the treatment was to slow the progression of development of spine deformity and obtain a prolongation of walking and standing ability. The indications for surgery were in relation to trauma in 17 cases or for progressive lower limb or spine deformity. In walking patients (21 cases) surgery was indicated only for contractures limiting walking ability. Surgery was also indicated in 35 cases soon after walking capability had ceased. In these cases correction of deformity allowed children to walk again with calipers for an average of 3 years. In 37 cases surgery was performed only to allow standing or to prevent or delay the development of spinal deformity. The indications for extensive spine fusion are discussed in relation to the speed of development of deformity, the pulmonary vital capacity, the dynamometric estimation of muscle strength, and the estimated duration of survival. Human, family and ethical factors are discussed.

One hundred and fifteen

    children
    AGE

 suffering from

    muscular dystrophy
    DIAGNOSIS

 had been

    treated surgically
    MEDICATION

 during the previous 12 years. The aim of the treatment was to slow the progression

    of development of spine deformity
    SYMPTOMS

 and obtain a

    prolongation of walking and standing ability
    SYMPTOMS

. The indications for

    surgery
    MEDICATION

 were in relation to

    trauma
    SYMPTOMS

 in 17 cases or for

    progressive lower limb or spine deformity
    SYMPTOMS

. In walking patients (21 cases)

    surgery
    MEDICATION

 was indicated only for

    contractures limiting walking ability
    SYMPTOMS

.

    Surgery
    MEDICATION

 was also indicated in 35 cases soon after

    walking capability had ceased
    SYMPTOMS

. In these cases

    correction of deformity
    MEDICATION

 allowed

    children
    AGE

    to walk again with calipers for an average of 3 years
    MEDICATION

. In 37 cases

    surgery was performed only to allow standing
    MEDICATION

 or to

    prevent or delay the development of spinal deformity
    SYMPTOMS

. The indications for

    extensive spine fusion
    MEDICATION

 are discussed in relation to the speed of development of deformity, the

    pulmonary vital capacity
    SYMPTOMS

, the

    dynamometric estimation of muscle strength
    PARACLINICAL

, and the estimated duration of survival. Human, family and ethical factors are discussed.


Malignant hyperpyrexia and Duchenne muscular dystrophy: A case report.

We report a patient with Duchenne muscular dystrophy who developed malignant hyperpyrexia during general anaesthesia. During anaesthesia bradycardia was followed by ventricular fibrillation, on which ventricular flutter supervened and a body temperature rise of 0.6 degrees C for 15 minutes, myoglobinuria and elevation of CPK level were observed. The caffeine sensitivity test of biopsied muscle fibers revealed an increase in sensitivity, although there was no sign of muscle rigidity during or after anaesthesia. Diagnosis of Duchenne muscular dystrophy was first established after the development of malignant hyperpyrexia in the present case as well as in previously reported cases. Determination of serum CPK is very important before general anaesthesia.

We report a patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who developed

    malignant hyperpyrexia
    SYMPTOMS

 during

    general anaesthesia
    MEDICATION

. During

    anaesthesia
    MEDICATION

    bradycardia
    SYMPTOMS

 was followed by

    ventricular fibrillation
    SYMPTOMS

, on which

    ventricular flutter supervened
    SYMPTOMS

 and a

    body temperature rise of 0.6 degrees C for 15 minutes
    SYMPTOMS

,

    myoglobinuria
    BIOCHEMICAL

 and

    elevation of CPK level
    BIOCHEMICAL

 were observed. The

    caffeine sensitivity test of biopsied muscle fibers
    PARACLINICAL

 revealed an

    increase in sensitivity
    BIOCHEMICAL

,

    although there was no sign of muscle rigidity during or after anaesthesia
    NEG_FINDINGS

. Diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

 was first established after the development of

    malignant hyperpyrexia
    SYMPTOMS

 in the present case as well as in previously reported cases.

    Determination of serum CPK
    PARACLINICAL

 is very important before

    general anaesthesia
    MEDICATION

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy

general anaesthesia
anaesthesia
general anaesthesia

myoglobinuria
elevation of CPK level
increase in sensitivity


Posterior tibial tendon transfer: a review of the literature and analysis of 74 procedures.

At Rancho Los Amigos Hospital on the Children's Orthopedic Service, 43 patients underwent anterior transfer of the posterior tibial tendon through the interosseous membrane between 1969 and 1979. This included 74 procedures for the following diagnoses: Duchenne muscular dystrophy, club-foot, cerebrospastic disease (cerebral palsy and head injury), Charcot-Marie-Tooth disease, scapuloperoneal dystrophy, and peroneal palsy. The purpose of this paper is to present the 54 of these transfers that have a minimum 2 year follow-up were performed with a uniform surgical technique, and had uniform postoperative management. This series is analyzed and compared with a review of the literature in order to set down guidelines for the use of the procedure. The analysis reveals that the patient with Duchenne muscular dystrophy who has decreasing gait function or brace fitting problems is the ideal candidate for the procedure with 26 of 28 satisfactory results. Gait electromyography was critical to the selection of the cerebrospastic patient for the transfer with those patients demonstrating swing-phase function of the posterior tibialis muscle yielding the best results. Finally, posterior tibial tendon transfer is generally not indicated in congenital clubfoot with six unsatisfactory results in 10 procedures, and the procedure should not be done in Charcot-Marie-Tooth disease as part of staged treatment that includes a possible future hindfoot stabilization.

At Rancho Los Amigos Hospital on the Children's Orthopedic Service, 43 patients underwent

    anterior transfer of the posterior tibial tendon through the interosseous membrane
    MEDICATION

 between 1969 and 1979. This included 74 procedures for the following diagnoses:

    Duchenne muscular dystrophy
    DIAGNOSIS

,

    club-foot
    DIAGNOSIS

,

    cerebrospastic disease (cerebral palsy and head injury)
    DIAGNOSIS

,

    Charcot-Marie-Tooth disease
    DIAGNOSIS

,

    scapuloperoneal dystrophy
    DIAGNOSIS

, and

    peroneal palsy
    DIAGNOSIS

. The purpose of this paper is to present the 54 of these transfers that have a minimum 2 year follow-up were performed with a uniform surgical technique, and had uniform postoperative management. This series is analyzed and compared with a review of the literature in order to set down guidelines for the use of the procedure. The analysis reveals that the patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who has

    decreasing gait function
    SYMPTOMS

 or

    brace fitting problems
    NEG_FINDINGS

 is the ideal candidate for the procedure with 26 of 28 satisfactory results.

    Gait electromyography
    PARACLINICAL

 was critical to the selection of the

    cerebrospastic
    DIAGNOSIS

 patient for the transfer with those patients demonstrating

    swing-phase function of the posterior tibialis muscle
    SYMPTOMS

 yielding the best results. Finally,

    posterior tibial tendon transfer
    MEDICATION

 is generally not indicated in

    congenital clubfoot
    DIAGNOSIS

 with six unsatisfactory results in 10 procedures, and the procedure should not be done in

    Charcot-Marie-Tooth disease
    DIAGNOSIS

 as part of

    staged treatment
    MEDICATION

 that includes a possible

    future hindfoot stabilization
    MEDICATION

.


Decreased A23187-induced chemiluminescence in Duchenne muscular dystrophy granulocytes.

A number of recent reports suggest that intracellular calcium concentration is increased in skeletal muscle in duchenne muscular dystrophy (DMD). Leucocyte chemiluminescent responses are dependent on calcium ions and can be induced by the calcium ionophore A23187. Chemiluminescence may therefore reflect intracellular calcium levels. In order to determine whether non-muscle cells in DMD share the calcium abnormality, we have examined A23187-induced chemiluminescence in DMD leucocytes. Peak calcium dependent chemiluminescence occurred at 0.25-0.75 mM added calcium chloride. Peak chemiluminescent responses in the 13-paired samples were reduced in DMD leucocytes (P less than 0.01) using a paired t-test. These result suggest that there is an abnormality of calcium dependent A23187-induced chemiluminescence in DMD leucocytes and that there may be a generalised abnormality of calcium metabolism in DMD.

A number of recent reports suggest that

    intracellular calcium concentration is increased in skeletal muscle
    MICROSCOPIC

 in

    duchenne muscular dystrophy (DMD)
    DIAGNOSIS

.

    Leucocyte chemiluminescent responses
    BIOCHEMICAL

 are dependent on

    calcium ions
    BIOCHEMICAL

 and can be induced by the calcium ionophore A23187.

    Chemiluminescence
    BIOCHEMICAL

 may therefore reflect

    intracellular calcium levels
    BIOCHEMICAL

. In order to determine whether

    non-muscle cells
    MICROSCOPIC

 in

    DMD
    DIAGNOSIS

 share the

    calcium abnormality
    BIOCHEMICAL

, we have examined

    A23187-induced chemiluminescence
    BIOCHEMICAL

 in

    DMD leucocytes
    MICROSCOPIC

.

    Peak calcium dependent chemiluminescence
    BIOCHEMICAL

 occurred at 0.25-0.75 mM added calcium chloride.

    Peak chemiluminescent responses
    BIOCHEMICAL

 in the 13-paired samples were

    reduced in DMD leucocytes
    BIOCHEMICAL

 (P less than 0.01) using a paired t-test. These result suggest that there is an

    abnormality of calcium dependent A23187-induced chemiluminescence in DMD
    BIOCHEMICAL

    leucocytes
    BIOCHEMICAL

 and that there may be a

    generalised abnormality of calcium metabolism
    BIOCHEMICAL

 in

    DMD
    DIAGNOSIS

.

duchenne muscular dystrophy (DMD)
DMD
DMD


Genetic linkage study of Duchenne muscular dystrophy and hemophilia A.

We studied a family in which three boys had both Duchenne muscular dystrophy and hemophilia A. Seven other males had only hemophilia A. Genetic linkage study showed a maximum likelihood estimate of recombination frequency of these two X-linked recessive traits of 0.16 with 95% confidence limits of 0.045 and 0.50. The loci of the two diseases may be closer than previous estimates.

We studied a

    family in which three boys
    FAMILY

    had both Duchenne muscular dystrophy
    FAMILY

 and hemophilia A. Seven other

    males
    GENDER

 had only hemophilia A.

    Genetic linkage study
    PARACLINICAL

 showed a maximum likelihood estimate of

    recombination frequency of these two X-linked recessive traits
    GENETICS

 of 0.16 with 95% confidence limits of 0.045 and 0.50. The loci of the two diseases may be closer than previous estimates.


Basilar artery occlusion in a case of Duchenne muscular dystrophy.

This is a report of a case of Duchenne muscular dystrophy (DMD), with multiple infarcts in the territories of the basilar artery. He developed abrupt vomiting and transient left hemiparesis at the age of 4 years. The episodes were seen 3 times between 4-year-1-month to 5-year-1-month old. Transaxial computerized tomography (CT) revealed multiple, well-defined but irregularly marginated areas of low density centered in the mid- and upper pons, right cerebral peduncle and thalamus. A right vertebral angiogram illustrated the narrowed basilar artery. The rectus femoris muscle was biopsied at the age of 4-year-1-month which showed marked variation in fiber size, myonecrosis with phagocytosis, central nuclei, and adipose and connective tissue proliferation, which were consistent with those seen in DMD. It remains unknown whether the basilar artery occlusion was an incidental event in this particular case or closely related to the disease process of DMD.

This is a report of a case of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, with

    multiple infarcts in the territories of the basilar artery
    SYMPTOMS

.

    He
    GENDER

 developed

    abrupt vomiting
    SYMPTOMS

 and

    transient left hemiparesis
    SYMPTOMS

 at the

    age of 4 years
    AGE

. The episodes were seen 3 times

    between 4-year-1-month to 5-year-1-month old
    AGE

.

    Transaxial computerized tomography (CT)
    PARACLINICAL

 revealed

    multiple, well-defined but irregularly marginated areas of low density centered in the mid- and upper pons, right cerebral peduncle and thalamus
    SYMPTOMS

. A

    right vertebral angiogram
    PARACLINICAL

 illustrated the

    narrowed basilar artery
    SYMPTOMS

.

    The rectus femoris muscle was biopsied
    PARACLINICAL

 at the

    age of 4-year-1-month
    AGE

 which showed

    marked variation in fiber size
    MICROSCOPIC

,

    myonecrosis with phagocytosis, central nuclei, and adipose and connective tissue proliferation
    MICROSCOPIC

, which were consistent with those seen in

    DMD
    DIAGNOSIS

. It remains unknown whether the

    basilar artery occlusion
    SYMPTOMS

 was an incidental event in this particular case or closely related to the disease process of

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
DMD