A case of limb-girdle muscular dystrophy with serum anti-nuclear antibody which led to a mistaken diagnosis of polymyositis.

A 45-year-old woman had first been diagnosed with polymyositis because of the presence of focal necrosis, regeneration and inflammatory infiltration in the muscle fibers, and elevated creatinine phosphokinase levels. However, a pathological re-evaluation and family history led to the definite diagnosis of limb-girdle muscular dystrophy (MD). This case suggests that MD should be taken into consideration in the differential diagnosis of the inflammatory myopathies and genetic surveys including dystrophin molecule may be necessary if the condition manifests during or after adolescence, or when the family history is uninformative. In this case, the serum anti-nuclear antibody was positive, and it may represent the first time that ANA positivity has been found in limb-girdle MD.

A

    45-year-old
    AGE

    woman
    GENDER

 had first been diagnosed with

    polymyositis
    DIAGNOSIS

 because of the presence of

    focal necrosis, regeneration and inflammatory infiltration in the muscle fibers
    MICROSCOPIC

, and

    elevated creatinine phosphokinase levels
    BIOCHEMICAL

. However, a

    pathological re-evaluation
    PARACLINICAL

 and

    family history
    PARACLINICAL

 led to the definite diagnosis of

    limb-girdle muscular dystrophy (MD)
    DIAGNOSIS

. This case suggests that

    MD
    DIAGNOSIS

 should be taken into consideration in the

    differential diagnosis
    PARACLINICAL

 of the

    inflammatory myopathies
    DIAGNOSIS

 and

    genetic surveys
    PARACLINICAL

 including

    dystrophin molecule
    PARACLINICAL

 may be necessary if the condition manifests

    during or after adolescence
    AGE

, or when the

    family history is uninformative
    NEG_FINDINGS

. In this case, the

    serum anti-nuclear antibody was positive
    BIOCHEMICAL

, and it may represent the first time that

    ANA positivity
    BIOCHEMICAL

 has been found in

    limb-girdle MD
    DIAGNOSIS

.

polymyositis
limb-girdle muscular dystrophy (MD)
MD
inflammatory myopathies
limb-girdle MD


[Typical electrocardiogram in atypical context. Or, when history and electrocardiogram are conclusive for a complex diagnosis].

A case of sudden death in an old female carrier of Duchenne muscular dystrophy is reported. Typical electrocardiographic features were registered without other signs or symptoms of heart involvement. In particular, cardiomyopathy was excluded by echocardiographic evaluation. We believe that in case of a typical electrocardiogram of Duchenne muscular dystrophy, a careful family medical history should be undertaken to exclude a carrier condition.

A case of

    sudden death
    SYMPTOMS

 in an

    old
    AGE

    female
    GENDER

 carrier of

    Duchenne muscular dystrophy
    DIAGNOSIS

 is reported.

    Typical electrocardiographic features
    SYMPTOMS

 were registered

    without other signs or symptoms of heart involvement
    NEG_FINDINGS

. In particular,

    cardiomyopathy was excluded by echocardiographic evaluation
    NEG_FINDINGS

. We believe that in case of a typical electrocardiogram of

    Duchenne muscular dystrophy
    DIAGNOSIS

, a

    careful family medical history
    PARACLINICAL

 should be undertaken to exclude a carrier condition.

sudden death
Typical electrocardiographic features

Duchenne muscular dystrophy
Duchenne muscular dystrophy


Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy.

We report a 5-year follow-up of two 4-year-old boys with classical Duchenne dystrophy, with an out-of-frame deletion in the Duchenne gene and absence of dystrophin in their muscle, who had a quite remarkable response to an intermittent, low-dosage, regime of prednisolone (0.75 mg/kg/day for 10 days each month, or alternating 10 days on and 10 days off). In the first case there was complete remission of all clinical signs of dystrophy, sustained almost fully up to the present time; in the second, the initial response was almost as marked, sustained for almost 5 years, before showing a fairly rapid decline over the ensuing year that resulted in loss of independent ambulation at the age of 10. Both boys remained around the 50th centile for height and weight, and showed no evidence of demineralization of bone on consecutive dual X-ray absorptiometry scanning of the spine, nor any signs of chronic prednisolone toxicity. These carefully documented individual cases suggest there may be an optimal window for treatment in the early stages of the disease, and further larger scale controlled studies should be targeted more selectively at this stage of the disease. This report also confirms that our regime of low dosage, intermittent prednisolone, with cycles of 10 days of treatment, either per month or alternating with 10 days off treatment, is well tolerated and can therefore be recommended for long-term use in children with Duchenne muscular dystrophy.

We report a 5-year follow-up of two

    4-year-old
    AGE

    boys
    GENDER

 with

    classical Duchenne dystrophy
    DIAGNOSIS

, with an

    out-of-frame deletion in the Duchenne gene
    GENETICS

 and

    absence of dystrophin in their muscle
    NEG_FINDINGS

, who had a quite remarkable response to an

    intermittent, low-dosage, regime of prednisolone (0.75 mg/kg/day for 10 days each month, or alternating 10 days on and 10 days off)
    MEDICATION

. In the first case there was

    complete remission of all clinical signs of dystrophy
    SYMPTOMS

    , sustained almost fully
    SYMPTOMS

 up to the present time; in the second, the

    initial response was almost as marked, sustained for almost 5 years
    SYMPTOMS

, before showing a

    fairly rapid decline
    SYMPTOMS

 over the ensuing year that resulted in

    loss of independent ambulation
    SYMPTOMS

 at the

    age of 10
    AGE

. Both

    boys
    GENDER

    remained around the 50th centile for height and weight
    SYMPTOMS

, and showed

    no evidence of demineralization of bone
    NEG_FINDINGS

 on

    consecutive dual X-ray absorptiometry scanning of the spine
    PARACLINICAL

,

    nor any signs of chronic prednisolone toxicity
    NEG_FINDINGS

. These carefully documented individual cases suggest there may be an optimal window for treatment in the early stages of the disease, and further larger scale controlled studies should be targeted more selectively at this stage of the disease. This report also confirms that our

    regime of low dosage, intermittent prednisolone, with cycles of 10 days of treatment, either per month or alternating with 10 days off treatment
    MEDICATION

, is well tolerated and can therefore be recommended for long-term use in

    children
    AGE

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

.

classical Duchenne dystrophy
Duchenne muscular dystrophy


Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30% of all DCM is thought to be inherited, while 70% is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484kb, total). Three putative new mutations (IVS5+1 G>T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5+1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.

    Dilated cardiomyopathy (DCM)
    DIAGNOSIS

 is the major indication for

    heart transplantation
    MEDICATION

. Approximately 30% of all

    DCM
    DIAGNOSIS

 is thought to be

    inherited
    GENETICS

, while 70% is

    sporadic
    DIAGNOSIS

.

    Mutations in the dystrophin gene
    GENETICS

 have been associated with the

    uncommon X-linked
    GENETICS

 form of

    DCM
    DIAGNOSIS

. We hypothesized that

    missense mutations and other less severe mutations of the dystrophin gene
    GENETICS

 might predispose to the common form of

    sporadic DCM
    DIAGNOSIS

. To test this hypothesis,

    22kb of genomic dystrophin DNA was scanned with DOVAM-S
    PARACLINICAL

 in each of the 22 patients with

    sporadic DCM
    DIAGNOSIS

    , including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484kb, total)
    PARACLINICAL

. Three

    putative new mutations (IVS5+1 G>T, K18N, and F3228L)
    GENETICS

 and

    seven polymorphisms
    GENETICS

 were identified. The

    splice site mutation IVS5+1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site
    GENETICS

.

    The missense mutations occur at amino acids that display substantial evolutionary conservation
    GENETICS

. Screening of 236 control individuals

    failed to identify these three mutations
    NEG_FINDINGS

. The three patients with

    putative mutations
    GENETICS

 had

    CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units
    BIOCHEMICAL

 while the 14 patients

    without mutations for which CK-MM were available
    NEG_FINDINGS

 had

    values ranging from 20 to 200
    BIOCHEMICAL

. The first comprehensive

    mutation scanning of the exons and splice junctions of the dystrophin gene
    PARACLINICAL

 in patients with

    sporadic DCM
    DIAGNOSIS

 presents the evidence that

    point mutations
    GENETICS

 are associated with

    sporadic DCM
    DIAGNOSIS

    without clinical evidence of skeletal myopathy
    NEG_FINDINGS

. It may be prudent to

    measure CK-MM
    PARACLINICAL

 in all patients with

    dilated cardiomyopathy
    DIAGNOSIS

 to identify candidates at high risk for

    dystrophin mutations
    GENETICS

.

Dilated cardiomyopathy (DCM)
DCM
sporadic
DCM
sporadic DCM
sporadic DCM
sporadic DCM
sporadic DCM
dilated cardiomyopathy


Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation.

Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder caused by mutations in the dystrophin gene. Studies have shown that bone marrow cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can become part of skeletal muscle myofibers. Whether human marrow cells also have this ability is unknown. Here we report the analysis of muscle biopsies from a DMD patient (DMD-BMT1) who received bone marrow transplantation at age 1 year for X-linked severe combined immune deficiency and who was diagnosed with DMD at age 12 years. Analysis of muscle biopsies from DMD-BMT1 revealed the presence of donor nuclei within a small number of muscle myofibers (0.5-0.9%). The majority of the myofibers produce a truncated, in-frame isoform of dystrophin lacking exons 44 and 45 (not wild-type). The presence of bone marrow-derived donor nuclei in the muscle of this patient documents the ability of exogenous human bone marrow cells to fuse into skeletal muscle and persist up to 13 years after transplantation.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    severe progressive muscle-wasting disorder
    DIAGNOSIS

 caused by

    mutations in the dystrophin gene
    GENETICS

. Studies have shown that bone marrow cells transplanted into

    lethally irradiated
    MEDICATION

 mdx mice, the mouse model of

    DMD
    DIAGNOSIS

,

    can become part of skeletal muscle myofibers
    MICROSCOPIC

. Whether

    human marrow cells
    MICROSCOPIC

 also have this ability is unknown. Here we report the

    analysis of muscle biopsies
    PARACLINICAL

 from a

    DMD
    DIAGNOSIS

 patient (

    DMD-BMT1
    DIAGNOSIS

) who

    received bone marrow transplantation
    MEDICATION

 at

    age 1 year
    AGE

 for

    X-linked severe combined immune deficiency
    GENETICS

 and who was diagnosed with

    DMD
    DIAGNOSIS

 at

    age 12 years
    AGE

.

    Analysis of muscle biopsies
    PARACLINICAL

 from

    DMD-BMT1
    DIAGNOSIS

 revealed the

    presence of donor nuclei within a small number of muscle myofibers (0.5-0.9%)
    MICROSCOPIC

.

    The majority of the myofibers produce a truncated, in-frame isoform of dystrophin lacking exons 44 and 45 (not wild-type)
    MICROSCOPIC

. The

    presence of bone marrow-derived donor nuclei in the muscle
    MICROSCOPIC

 of this patient documents the ability of

    exogenous human bone marrow cells to fuse into skeletal muscle
    MICROSCOPIC

 and persist up to 13 years after

    transplantation
    MEDICATION

.

lethally irradiated
received bone marrow transplantation
transplantation


[Application of bispectral index (BIS) monitoring to anesthetic management of posterior spinal fusion in a patient with Duchenne muscular dystrophy].

A 12-year-old boy with Duchenne muscular dystrophy underwent posterior spinal fusion for progressive scoliosis. Preoperative evaluation was focused on respiratory function as well as cardiac function, which revealed markedly reduced respiratory reserve (FVC 0.77 l, %FVC 25.9%, FEV1.0 0.48 l, %FEV1.0 62%) and well-preserved biventricular function. A possible association between malignant hyperthermia and Duchenne muscular dystrophy has been documented. Thus anesthesia was administered without triggering agents. Propofol and fentanyl were used for induction and maintenance of anesthesia, and the patient was ventilated with O2-nitrous oxide mixture. The anesthesia machine, prepared by using a disposable circuit and fresh CO2-absorbent and disconnecting the vaporizers, was flushed with O2 at a rate of 10 l.min-1 for 20 minutes before use. A small dose of vecuronium was administered while monitoring the train-of-four ratio. The bispectral index (BIS) was utilized to optimize the depth of anesthesia so that the wake-up test could be performed promptly on surgeon's request while avoiding the intraoperative awareness. The BIS was helpful in continuously assessing the wakening process. BIS increased from 40's to 80's in 15 minutes after discontinuation of propofol and nitrous oxide during the test. The patient was kept under close observation postoperatively without any sign of malignant hyperthermia.

A

    12-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 underwent

    posterior spinal fusion
    MEDICATION

 for

    progressive scoliosis
    DIAGNOSIS

. Preoperative evaluation was focused on

    respiratory function
    PARACLINICAL

 as well as

    cardiac function
    PARACLINICAL

, which revealed

    markedly reduced respiratory reserve (FVC 0.77 l, %FVC 25.9%, FEV1.0 0.48 l, %FEV1.0 62%)
    SYMPTOMS

 and

    well-preserved biventricular function
    SYMPTOMS

. A possible association between

    malignant hyperthermia
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

 has been documented. Thus

    anesthesia
    MEDICATION

 was administered

    without triggering agents
    NEG_FINDINGS

.

    Propofol and fentanyl
    MEDICATION

 were used for

    induction and maintenance of anesthesia
    MEDICATION

, and the patient was

    ventilated with O2-nitrous oxide mixture
    MEDICATION

. The

    anesthesia machine
    MEDICATION

, prepared by using a

    disposable circuit and fresh CO2-absorbent and disconnecting the vaporizers
    MEDICATION

, was

    flushed with O2 at a rate of 10 l.min-1 for 20 minutes
    MEDICATION

 before use. A

    small dose of vecuronium
    MEDICATION

 was administered while

    monitoring the train-of-four ratio
    PARACLINICAL

. The

    bispectral index (BIS)
    PARACLINICAL

 was utilized to optimize the

    depth of anesthesia
    MEDICATION

 so that the

    wake-up test
    PARACLINICAL

 could be performed promptly on surgeon's request while avoiding the intraoperative awareness. The

    BIS
    PARACLINICAL

 was helpful in continuously assessing the wakening process.

    BIS increased from 40's to 80's
    SYMPTOMS

 in 15 minutes after

    discontinuation of propofol and nitrous oxide
    MEDICATION

 during the test. The patient was kept under close observation postoperatively

    without any sign of malignant hyperthermia
    NEG_FINDINGS

.

Duchenne muscular dystrophy
progressive scoliosis
malignant hyperthermia
Duchenne muscular dystrophy


The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation.

A male patient with profound mental retardation, athetosis, nystagmus, and severe congenital hypotonia (Duchenne muscular dystrophy [DMD]) was previously shown to carry a pericentric inversion of the X chromosome, 46,Y,inv(X)(p21.2q22.2). His mother carried this inversion on one X allele. The patient's condition was originally misdiagnosed as cerebral palsy, and only later was it diagnosed as DMD. Because the DMD gene is located at Xp21.2, which is one breakpoint of the inv(X), and because its defects are rarely associated with severe mental retardation, the other clinical features of this patient were deemed likely to be associated with the opposite breakpoint at Xq22. Our precise molecular-cytogenetic characterization of both breakpoints revealed three catastrophic genetic events that had probably influenced neuromuscular and cognitive development: deletion of part of the DMD gene at Xp21.2, duplication of the human proteolipid protein gene (PLP) at Xq22.2, and disruption of a novel gene. The latter sequence, showing a high degree of homology to the Sec4 gene of yeast, encoded a putative small guanine-protein, Ras-like GTPase that we have termed "RLGP." Immunocytochemistry located RLGP at mitochondria. We speculate that disruption of RLGP was responsible for the patient's profound mental retardation.

A

    male
    GENDER

 patient with

    profound mental retardation
    SYMPTOMS

,

    athetosis
    SYMPTOMS

,

    nystagmus
    SYMPTOMS

, and

    severe congenital hypotonia
    SYMPTOMS

 (

    Duchenne muscular dystrophy [DMD]
    DIAGNOSIS

) was previously shown to carry a

    pericentric inversion of the X chromosome, 46,Y,inv(X)(p21.2q22.2)
    GENETICS

.

    His
    GENDER

    mother carried this inversion on one X allele
    FAMILY

. The patient's condition was originally

    misdiagnosed as cerebral palsy
    NEG_FINDINGS

, and only later was it diagnosed as

    DMD
    DIAGNOSIS

. Because

    the DMD gene is located at Xp21.2, which is one breakpoint of the inv(X)
    GENETICS

, and because its defects are rarely associated with

    severe mental retardation
    NEG_FINDINGS

, the other clinical features of this patient were deemed likely to be associated with the

    opposite breakpoint at Xq22
    GENETICS

. Our

    precise molecular-cytogenetic characterization of both breakpoints
    PARACLINICAL

 revealed three

    catastrophic genetic events
    GENETICS

 that had probably influenced

    neuromuscular and cognitive development
    SYMPTOMS

:

    deletion of part of the DMD gene at Xp21.2
    GENETICS

,

    duplication of the human proteolipid protein gene (PLP) at Xq22.2
    GENETICS

, and

    disruption of a novel gene
    GENETICS

. The

    latter sequence, showing a high degree of homology to the Sec4 gene of yeast
    GENETICS

, encoded a

    putative small guanine-protein, Ras-like GTPase
    GENETICS

 that we have termed "RLGP."

    Immunocytochemistry
    PARACLINICAL

    located RLGP at mitochondria
    MICROSCOPIC

. We speculate that

    disruption of RLGP
    GENETICS

 was responsible for the patient's

    profound mental retardation
    SYMPTOMS

.

profound mental retardation
athetosis
nystagmus
severe congenital hypotonia
neuromuscular and cognitive development
profound mental retardation

misdiagnosed as cerebral palsy
severe mental retardation


Successful bridge to transplantation in a patient with Becker muscular dystrophy-associated cardiomyopathy.

A 28-year-old male patient diagnosed with Becker muscular dystrophy (BMD)-associated cardiomyopathy was successfully bridged to transplantation with the Cardiowest total artificial heart. Dramatic improvement of muscular functional status occurred following transplantation.

A

    28-year-old
    AGE

    male
    GENDER

 patient diagnosed with

    Becker muscular dystrophy (BMD)-associated cardiomyopathy
    DIAGNOSIS

 was successfully

    bridged to transplantation with the Cardiowest total artificial heart
    MEDICATION

.

    Dramatic improvement of muscular functional status
    SYMPTOMS

 occurred following

    transplantation
    MEDICATION

.


[Muscular dystrophy due to a deficit of gamma-sarcoglycan. A report of three patients with the Delta-521t mutation].

gamma-sarcoglicanopathies, also classified as limb girdle muscular dystrophy type 2C (LGMD2C) are a group of autosomal recessive muscular dystrophies due to mutations in 13q12 and subsequent g sarcoglican deficiency. The protein is one of the components of the dystrophin associated glycoprotein complex and is thought to impart structural integrity to the myofibre. The clinical course of the disease may be heterogeneous, ranging from severe forms with onset in the first decade and rapid progression resembling Progressive Duchenne muscular dystrophy (DMD) to milder forms with later onset and slower course. Cases hitherto reported in Spain corresponds to gypsie patients, homozygous for C283Y missense mutation.

Here, we report three new galician (Northwest Spain) patients (one male and one female sibling cases) with a severe DMD like muscular dystrophy homozygous for D 521T. In the first male familial case, initial diagnosis of DMD was made. On reevaluation fourteen years later, inmunohistochemical and molecular studies allowed for a definitive g sarcoglicanopathy diagnosis.

Patients with a primary sarcoglycanopathy may be clinically indistinguishable from those with the primary dystrophinopathies. Probably, the diagnosis of LGMD are underestimated and a number of male patients diagnosed as DMD really corresponds to a recessive form o muscular dystrophy. Consequently, a definitive diagnosis rests on appropriate inmunohistochemical and molecular analysis, specially in those patients showing a normal pattern of dystrophin and/or suggestive for an autosomal recessive mode of inheritance.

    gamma-sarcoglicanopathies
    DIAGNOSIS

, also classified as

    limb girdle muscular dystrophy type 2C (LGMD2C)
    DIAGNOSIS

 are a group of

    autosomal recessive
    GENETICS

    muscular dystrophies
    DIAGNOSIS

 due to

    mutations in 13q12
    GENETICS

 and subsequent

    g sarcoglican deficiency
    BIOCHEMICAL

. The protein is one of the components of the dystrophin associated glycoprotein complex and is thought to impart structural integrity to the

    myofibre
    MICROSCOPIC

. The clinical course of the disease may be heterogeneous, ranging from severe forms with

    onset in the first decade
    AGE

 and

    rapid progression
    SYMPTOMS

 resembling

    Progressive Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 to milder forms with later onset and slower course. Cases hitherto reported in

    Spain
    ETHNICITY

 corresponds to

    gypsie
    DIAGNOSIS

 patients,

    homozygous for C283Y missense mutation
    GENETICS

.

Here, we report three new

    galician
    ETHNICITY

 (

    Northwest Spain
    ETHNICITY

) patients (one

    male
    GENDER

 and one

    female
    GENDER

    sibling cases
    FAMILY

) with a

    severe DMD like muscular dystrophy
    DIAGNOSIS

 homozygous for D 521T. In the first

    male
    GENDER

 familial case, initial diagnosis of

    DMD
    DIAGNOSIS

 was made. On reevaluation fourteen years later,

    inmunohistochemical and molecular studies
    PARACLINICAL

 allowed for a definitive

    g sarcoglicanopathy
    DIAGNOSIS

 diagnosis.

Patients with a

    primary sarcoglycanopathy
    DIAGNOSIS

 may be clinically indistinguishable from those with the

    primary dystrophinopathies
    DIAGNOSIS

. Probably, the diagnosis of

    LGMD
    DIAGNOSIS

 are underestimated and a number of

    male
    GENDER

 patients diagnosed as

    DMD
    DIAGNOSIS

 really corresponds to a

    recessive form o muscular dystrophy
    DIAGNOSIS

. Consequently, a definitive diagnosis rests on appropriate

    inmunohistochemical and molecular analysis
    PARACLINICAL

, specially in those patients showing a

    normal pattern of dystrophin
    NEG_FINDINGS

 and/or suggestive for an

    autosomal recessive mode of inheritance
    GENETICS

.

autosomal recessive
mutations in 13q12
homozygous for C283Y missense mutation
autosomal recessive mode of inheritance


Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy.

Despite numerous reports about dystrophin alterations in Duchenne and Becker muscular dystrophies and dilated cardiomyopathy, the function of dystrophin gene promoters has not yet been completely elucidated. We report the first case of a DNA segment deletion encompassing promoters M and P of the human dystrophin gene, which caused a very severe muscle phenotype without cardiomyopathy, in a 13-year-old boy. These data indicate that the simultaneous lack of promoters P and M results in dramatic consequences in skeletal muscle but not in the heart.

Despite numerous reports about

    dystrophin alterations
    GENETICS

 in

    Duchenne
    DIAGNOSIS

 and

    Becker muscular dystrophies
    DIAGNOSIS

 and

    dilated cardiomyopathy
    DIAGNOSIS

, the function of

    dystrophin gene promoters
    GENETICS

 has not yet been completely elucidated. We report the first case of a

    DNA segment deletion encompassing promoters M and P of the human dystrophin gene
    GENETICS

, which caused a

    very severe muscle phenotype
    SYMPTOMS

    without cardiomyopathy
    NEG_FINDINGS

, in a

    13-year-old
    AGE

    boy
    GENDER

. These data indicate that the

    simultaneous lack of promoters P and M
    GENETICS

 results in

    dramatic consequences in skeletal muscle but not in the heart
    SYMPTOMS

.

Duchenne
Becker muscular dystrophies
dilated cardiomyopathy


Becker muscular dystrophy-related cardiomyopathy: a favorable response to medical therapy.

Patients with Becker muscular dystrophy-related cardiomyopathy typically survive into their 30s, when they succumb to complications of cardiomyopathy or receive heart transplants. The cardiomyopathy is related to an abnormality in the protein dystrophin; no successful medical responses have been reported to date. We describe a patient with Becker muscular dystrophy-related cardiomyopathy in whom we noted improvement of cardiac status with carefully titrated medical therapy. Successful therapy suggests a trial of medical therapy may be beneficial when patients with Becker muscular dystrophy-related cardiomyopathy are evaluated for transplant.

Patients with

    Becker muscular dystrophy-related cardiomyopathy
    DIAGNOSIS

 typically survive

    into their 30s
    AGE

, when they succumb to

    complications of cardiomyopathy
    SYMPTOMS

 or receive

    heart transplants
    MEDICATION

. The

    cardiomyopathy
    DIAGNOSIS

 is related to an

    abnormality in the protein dystrophin
    GENETICS

; no successful medical responses have been reported to date. We describe a patient with

    Becker muscular dystrophy-related cardiomyopathy
    DIAGNOSIS

 in whom we noted

    improvement of cardiac status
    SYMPTOMS

 with

    carefully titrated medical therapy
    MEDICATION

. Successful therapy suggests a

    trial of medical therapy
    MEDICATION

 may be beneficial when patients with

    Becker muscular dystrophy-related cardiomyopathy
    DIAGNOSIS

 are evaluated for

    transplant
    MEDICATION

.

complications of cardiomyopathy
improvement of cardiac status

heart transplants
carefully titrated medical therapy
trial of medical therapy
transplant


[Sevoflurane can induce rhabdomyolysis in Duchenne's muscular dystrophy].

Rhabdomyolysis is one of the perioperative complications in patients with Duchenne's muscular dystrophy (DMD). It has been suggested that sevoflurane can be used safely for anesthesia in patients with DMD. In this report, we describe a case with DMD who received anesthesia with sevoflurane, in which rhabdomyolysis developed postoperatively. A 6-year-old boy diagnosed as DMD was scheduled for tonsillectomy under general anesthesia. Preoperative laboratory examination revealed a high level of creatine kinase (CK) (16,000-32,000 IU.l-1). An abnormality of the dystrophin gene was detected by DNA analysis. Anesthesia was induced with sevoflurane without muscle relaxant, and maintained with sevoflurane in nitrous oxide and oxygen under controlled ventilation. The course of anesthesia was uneventful and the patient recovered smoothly. Three hours postoperatively, dark red urine with a high concentration of myoglobin (1,390,000 ng.ml-1) was recognized with a high level of CK (63,500 IU.l-1). Body temperature was 37.6 degrees C, and electrocardiogram and serum potassium were within normal ranges. After the diuresis with mannitol and furosemide, the urine became clear. On the 4th postoperative day, he was discharged without any complication. This case suggested that rhabdomyolysis can develop after sevoflurane anesthesia in patients with DMD.

    Rhabdomyolysis
    DIAGNOSIS

 is one of the perioperative complications in patients with

    Duchenne's muscular dystrophy (DMD)
    DIAGNOSIS

. It has been suggested that

    sevoflurane
    MEDICATION

 can be used safely for

    anesthesia
    MEDICATION

 in patients with

    DMD
    DIAGNOSIS

. In this report, we describe a case with

    DMD
    DIAGNOSIS

 who received

    anesthesia with sevoflurane
    MEDICATION

, in which

    rhabdomyolysis
    DIAGNOSIS

 developed postoperatively. A

    6-year-old
    AGE

    boy
    GENDER

 diagnosed as

    DMD
    DIAGNOSIS

 was scheduled for

    tonsillectomy
    MEDICATION

 under

    general anesthesia
    MEDICATION

. Preoperative

    laboratory examination
    PARACLINICAL

 revealed a

    high level of creatine kinase (CK) (16,000-32,000 IU.l-1)
    BIOCHEMICAL

. An

    abnormality of the dystrophin gene
    GENETICS

 was detected by

    DNA analysis
    PARACLINICAL

.

    Anesthesia
    MEDICATION

 was

    induced with sevoflurane
    MEDICATION

    without muscle relaxant
    NEG_FINDINGS

, and

    maintained with sevoflurane in nitrous oxide and oxygen under controlled ventilation
    MEDICATION

. The course of anesthesia was uneventful and the patient recovered smoothly. Three hours postoperatively,

    dark red urine with a high concentration of myoglobin (1,390,000 ng.ml-1) was recognized
    BIOCHEMICAL

 with a

    high level of CK (63,500 IU.l-1)
    BIOCHEMICAL

.

    Body temperature was 37.6 degrees C
    SYMPTOMS

, and

    electrocardiogram and serum potassium were within normal ranges
    NEG_FINDINGS

. After the

    diuresis with mannitol and furosemide
    MEDICATION

, the

    urine became clear
    BIOCHEMICAL

. On the 4th postoperative day,

    he
    GENDER

 was discharged

    without any complication
    NEG_FINDINGS

. This case suggested that

    rhabdomyolysis
    DIAGNOSIS

 can develop after

    sevoflurane anesthesia
    MEDICATION

 in patients with

    DMD
    DIAGNOSIS

.

Rhabdomyolysis
Duchenne's muscular dystrophy (DMD)
DMD
DMD
rhabdomyolysis
DMD
rhabdomyolysis
DMD


[Pathogenetic role of intestinal microbiocenosis in the pathogenesis of hereditary myodystrophy].

The effect of the inclusion of probiotic preparations for the correction of disturbances in normal intestinal microflora into the complex therapy of patients wish Duchenne's childhood muscular dystrophy and Becker's myopathy was analyzed. Probiotic therapy made it possible to improve the clinical state of patients, manifested by an increase in muscular strength and accompanied by positive shifts in electromyographic, immunological, biochemical, hormonal characteristics. Intestinal microbiocenosis plays seemingly a certain role in the formation of hereditary pathology.

The effect of the

    inclusion of probiotic preparations
    MEDICATION

 for the correction of

    disturbances in normal intestinal microflora
    BIOCHEMICAL

    into the complex therapy
    MEDICATION

 of patients wish

    Duchenne's childhood muscular dystrophy
    DIAGNOSIS

 and

    Becker's myopathy
    DIAGNOSIS

 was analyzed.

    Probiotic therapy
    MEDICATION

 made it possible to improve the clinical state of patients, manifested by an

    increase in muscular strength
    SYMPTOMS

 and accompanied by

    positive shifts in electromyographic, immunological, biochemical, hormonal characteristics
    SYMPTOMS

.

    Intestinal microbiocenosis
    MICROSCOPIC

 plays seemingly a certain role in the formation of

    hereditary pathology
    GENETICS

.

inclusion of probiotic preparations
into the complex therapy
Probiotic therapy

Duchenne's childhood muscular dystrophy
Becker's myopathy


Adhalin deficiency: an unusual cause of muscular dystrophy.

Childhood muscular dystrophies have a wide clinical spectrum, motor disability and are variably inherited. Although the phenotype may appear similar they may represent distinct genetic entities. Advances in immunohistochemistry, gene deletion and linkage studies have enabled precise characterization. We report a family with an early onset weakness and calf pseudo hypertrophy in 2 male sibs with an usually mild course. Deletion screening was negative for 24 exons of the DMD gene in both. Muscle immunohistochemistry revealed normal dystrophin I and II staining but complete absence for adhalin, a dystrophin associated glycoprotein. Classifying them as adhalinopathy. Severe childhood autosomal recessive muscular dystrophies (SCARMD) result from mutation in the sarcoglycan complex (59). Adhalinopathy is now used to describe SCARMD. The adhalinopathy described in our patients is the first report from India.

    Childhood muscular dystrophies
    DIAGNOSIS

 have a wide clinical spectrum,

    motor disability
    SYMPTOMS

 and are

    variably inherited
    GENETICS

. Although the phenotype may appear similar they may represent distinct genetic entities. Advances in

    immunohistochemistry
    PARACLINICAL

,

    gene deletion
    PARACLINICAL

 and

    linkage studies
    PARACLINICAL

 have enabled precise characterization. We report a

    family with
    FAMILY

 an

    early onset weakness
    SYMPTOMS

 and

    calf pseudo hypertrophy
    SYMPTOMS

    in 2 male sibs with an usually mild course
    FAMILY

.

    Deletion screening was negative for 24 exons of the DMD gene
    PARACLINICAL

 in both.

    Muscle immunohistochemistry
    PARACLINICAL

 revealed

    normal dystrophin I and II staining
    NEG_FINDINGS

 but

    complete absence for adhalin, a dystrophin associated glycoprotein
    BIOCHEMICAL

. Classifying them as

    adhalinopathy
    DIAGNOSIS

.

    Severe childhood autosomal recessive muscular dystrophies
    DIAGNOSIS

 (

    SCARMD)
    DIAGNOSIS

 result from

    mutation in the sarcoglycan complex (59)
    GENETICS

.

    Adhalinopathy
    DIAGNOSIS

 is now used to describe

    SCARMD
    DIAGNOSIS

. The

    adhalinopathy
    DIAGNOSIS

 described in our patients is the first report from

    India
    ETHNICITY

.

motor disability
early onset weakness
calf pseudo hypertrophy


Non-Hodgkin's lymphoma of the ascending colon in a patient with becker muscular dystrophy: report of a case.

We herein present the findings of a 10-year-old boy with non-Hodgkin's lymphoma of the ascending colon which caused intussusception and intestinal bleeding. He had a history of Becker muscular dystrophy. However, he had neither hypertrophic calves nor cardiomyopathy, and his serum creatine kinase (CK) level always exceeded 2000 IU/l. Preoperatively, a laboratory examination revealed high serum levels of CK (2038IU/l), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and the blood hemoglobin level was 7.0g/dl. A barium enema examination revealed an intussusception in his ascending colon, which was found to be a highly vascular tumor on Doppler ultrasound scans. A right hemicolectomy was performed. Macroscopically, the 5 x 6 x 8-cm solid tumor of the ascending colon resembled a submucosal tumor and had two ulcerous lesions at the tip. The tumor was histologically diagnosed to be a diffuse large B-cell lymphoma of the ascending colon. General examinations revealed no involvement of lymphoma postoperatively. At 13 months after surgery, the CK (37861U/l), AST (110lU/l), ALT (1381U/ l), and LDH (420lU/l) levels are still high, and the patient is doing well without any signs of recurrence.

We herein present the findings of a

    10-year-old
    AGE

    boy
    GENDER

 with

    non-Hodgkin's lymphoma of the ascending colon
    DIAGNOSIS

 which caused

    intussusception
    SYMPTOMS

 and

    intestinal bleeding
    SYMPTOMS

.

    He
    GENDER

 had a history of

    Becker muscular dystrophy
    DIAGNOSIS

. However,

    he
    GENDER

 had

    neither hypertrophic calves
    NEG_FINDINGS

 nor

    cardiomyopathy
    SYMPTOMS

, and his serum creatine kinase (CK) level always exceeded 2000 IU/l. Preoperatively, a

    laboratory examination
    PARACLINICAL

 revealed

    high serum levels of CK (2038IU/l), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH)
    BIOCHEMICAL

, and the

    blood hemoglobin level was 7.0g/dl
    BIOCHEMICAL

. A

    barium enema examination
    PARACLINICAL

 revealed an

    intussusception in his ascending colon
    SYMPTOMS

, which was found to be a

    highly vascular tumor
    SYMPTOMS

 on

    Doppler ultrasound scans
    PARACLINICAL

. A

    right hemicolectomy
    MEDICATION

 was performed. Macroscopically, the

    5 x 6 x 8-cm solid tumor of the ascending colon resembled a submucosal tumor
    SYMPTOMS

 and

    had two ulcerous lesions at the tip
    SYMPTOMS

. The tumor was histologically diagnosed to be a

    diffuse large B-cell lymphoma of the ascending colon
    DIAGNOSIS

.

    General examinations
    PARACLINICAL

 revealed

    no involvement of lymphoma postoperatively
    NEG_FINDINGS

. At 13 months after

    surgery
    MEDICATION

,

    the CK (37861U/l), AST (110lU/l), ALT (1381U/ l), and LDH (420lU/l) levels are still high
    BIOCHEMICAL

, and the patient is doing well

    without any signs of recurrence
    NEG_FINDINGS

.


Spontaneous left ventricular hypertrabeculation in dystrophin duplication based Becker's muscular dystrophy.

Left ventricular hypertrabeculation is frequently associated with neuromuscular disorders. Whether left ventricular hypertrabeculation in these patients is congenital or develops during lifetime, is unknown.

In a 65-year-old man with Becker's muscular dystrophy, due to a duplication in the dystrophin gene on chromosome Xq21 (dystrophin molecular weight: 500 kD), left ventricular hypertrabeculation was detected on transthoracic echocardiography although being absent in repeated previous echocardiographic examinations. Additionally, there was thickening of the left ventricular myocardium. The spontaneous occurrence of left ventricular hypertrabeculation was interpreted as progression of cardiac involvement in Becker's muscular dystrophy.

Left ventricular hypertrabeculation may not exclusively be congenital, but may occasionally develop spontaneously during lifetime, being interpreted as progression of cardiac involvement in Becker's muscular dystrophy.

    Left ventricular hypertrabeculation
    SYMPTOMS

 is frequently associated with

    neuromuscular disorders
    DIAGNOSIS

. Whether

    left ventricular hypertrabeculation
    SYMPTOMS

 in these patients is congenital or develops during lifetime, is unknown.

In a

    65-year-old
    AGE

    man
    GENDER

 with

    Becker's muscular dystrophy
    DIAGNOSIS

, due to a

    duplication in the dystrophin gene on chromosome Xq21 (dystrophin molecular weight: 500 kD)
    GENETICS

,

    left ventricular hypertrabeculation
    SYMPTOMS

 was detected on

    transthoracic echocardiography
    PARACLINICAL

    although being absent in repeated previous echocardiographic examinations
    NEG_FINDINGS

. Additionally, there was

    thickening of the left ventricular myocardium
    SYMPTOMS

. The spontaneous occurrence of

    left ventricular hypertrabeculation
    SYMPTOMS

 was interpreted as progression of

    cardiac involvement
    SYMPTOMS

 in

    Becker's muscular dystrophy
    DIAGNOSIS

.

    Left ventricular hypertrabeculation
    SYMPTOMS

 may not exclusively be congenital, but may occasionally develop spontaneously during lifetime, being interpreted as progression of

    cardiac involvement
    SYMPTOMS

 in

    Becker's muscular dystrophy
    DIAGNOSIS

.

neuromuscular disorders
Becker's muscular dystrophy
Becker's muscular dystrophy
Becker's muscular dystrophy


Prednisone therapy in Becker's muscular dystrophy.

Two boys with Becker's muscular dystrophy had a dramatic and sustained improvement in strength with therapeutic use of pred nisone. Both had documented Xp-21 defects on DNA testing. Concurrently with improvement, there was a decrease in their serum creatine kinase levels. One patient had two muscle biopsies, the first before prednisone treatment and the second during treatment. Both biopsies demonstrated an immunoblot decrease in the quantity of muscle dystrophin. Routine histology on the first biopsy was consistent with muscle dystrophy, and the second biopsy was normal. These two patients suggest that a small percentage of patients with Becker's muscular dystrophy have a dramatic and sus tained improvement in strength with the use of therapeutic corticosteroids. All patients with Becker's muscular dystrophy should be given a careful trial of prednisone to define those who benefit.

Two

    boys
    GENDER

 with

    Becker's muscular dystrophy
    DIAGNOSIS

 had a

    dramatic and sustained improvement in strength
    SYMPTOMS

 with

    therapeutic use of pred nisone
    MEDICATION

. Both had documented

    Xp-21 defects
    GENETICS

 on

    DNA testing
    PARACLINICAL

. Concurrently with improvement, there was a

    decrease in their serum creatine kinase levels
    BIOCHEMICAL

. One patient had

    two muscle biopsies
    PARACLINICAL

, the first before

    prednisone treatment
    MEDICATION

 and the second during treatment. Both biopsies demonstrated an

    immunoblot decrease in the quantity of muscle dystrophin
    BIOCHEMICAL

.

    Routine histology on the first biopsy
    PARACLINICAL

 was consistent with

    muscle dystrophy
    DIAGNOSIS

, and the second

    biopsy was normal
    NEG_FINDINGS

. These two patients suggest that a small percentage of patients with

    Becker's muscular dystrophy
    DIAGNOSIS

 have a dramatic and

    sus tained improvement in strength
    SYMPTOMS

 with the use of

    therapeutic corticosteroids
    MEDICATION

. All patients with

    Becker's muscular dystrophy
    DIAGNOSIS

 should be given a careful trial of

    prednisone
    MEDICATION

 to define those who benefit.

Becker's muscular dystrophy
muscle dystrophy
Becker's muscular dystrophy
Becker's muscular dystrophy

therapeutic use of pred nisone
prednisone treatment
therapeutic corticosteroids
prednisone


Long mutant dystrophins and variable phenotypes: evasion of nonsense-mediated decay?

More than 98% of Duchenne muscular dystrophy (DMD) mutations result in the premature termination of the dystrophin open reading frame at various points over its 11-kb length. Despite this wide variation in coding potential (0%-98.6% of the full-length protein), the truncating mutations are associated with a surprisingly uniform severity of phenotype. This uniformity is probably attributable to ablation of the message by nonsense-mediated decay (NMD). The rare truncating mutations that occur near the 3' end of the dystrophin gene (beyond exon 70) can however result in extremely variable phenotypes (both intra- and inter-familially). We suggest that all proteins encoded by such mutant genes are capable in principle of rescuing the DMD phenotype but that NMD abrogates the opportunity to effect this rescue. The observed variability may therefore reflect an underlying variation in the efficiency of NMD between individuals. We discuss this hypothesis with particular reference to a well-characterised Becker muscular dystrophy patient with a frameshift mutation, where expression of a truncated dystrophin rescues the muscular but not mental phenotype.

More than 98% of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 mutations result in the

    premature termination of the dystrophin open reading frame at various points over its 11-kb length
    GENETICS

. Despite this wide variation in coding potential (

    0%-98.6% of the full-length protein)
    GENETICS

, the

    truncating mutations
    GENETICS

 are associated with a surprisingly uniform severity of phenotype. This uniformity is probably attributable to ablation of the message by

    nonsense-mediated decay (NMD)
    NEG_FINDINGS

. The

    rare truncating mutations that occur near the 3' end of the dystrophin gene (beyond exon 70)
    GENETICS

 can however result in extremely variable phenotypes (both intra- and inter-familially). We suggest that all proteins encoded by such mutant genes are capable in principle of rescuing the DMD phenotype but that NMD abrogates the opportunity to effect this rescue. The observed variability may therefore reflect an underlying variation in the efficiency of NMD between individuals. We discuss this hypothesis with particular reference to a well-characterised

    Becker muscular dystrophy
    DIAGNOSIS

 patient with a

    frameshift mutation
    GENETICS

, where expression of a truncated dystrophin

    rescues the muscular but not mental phenotype
    SYMPTOMS

.

Duchenne muscular dystrophy (DMD)
Becker muscular dystrophy


Late onset and very mild course of Xp21 Becker type muscular dystrophy.

We report a case of late onset of Becker's muscular dystrophy (BMD), diagnosed at the age of 60, which showed a very mild clinical course. Remarkably, the immunohistochemical pattern did not show significant alterations, while Western blotting disclosed low molecular weight dystrophin. DNA analysis showed a deletion of the exons 45-53 of the Xp21 gene, which is fairly typical of Becker's muscular dystrophy but not predictable of clinical course. The possibility of Xp21 muscular dystrophy must be considered in all myopathies of uncertain cause, also in elderly patients.

We report a case of

    late onset of Becker's muscular dystrophy (BMD)
    DIAGNOSIS

, diagnosed at the

    age of 60
    AGE

, which showed a

    very mild clinical course
    SYMPTOMS

. Remarkably, the

    immunohistochemical pattern did not show significant alterations
    NEG_FINDINGS

, while

    Western blotting
    PARACLINICAL

 disclosed

    low molecular weight dystrophin
    BIOCHEMICAL

.

    DNA analysis
    PARACLINICAL

 showed a

    deletion of the exons 45-53 of the Xp21 gene, which is
    GENETICS

 fairly typical of

    Becker's muscular dystrophy
    DIAGNOSIS

 but not predictable of clinical course. The possibility of

    Xp21 muscular dystrophy
    DIAGNOSIS

 must be considered in all

    myopathies
    DIAGNOSIS

 of uncertain cause, also in

    elderly
    AGE

 patients.


Normalization of creatine kinase level during pregnancy in idiopathic hyperCKemia.

A 34-year-old previously healthy woman with no remarkable family history developed asymptomatic hyperCKemia at age 26. Over the next 6 years, hyperCKemia persisted (502-2562 IU/l; normal range<180). A muscle biopsy showed minimal nonspecific myopathy. Genetic analysis of blood and muscle samples showed no abnormality in the dystrophin gene. At age 33, she became pregnant for the first time and serum creatine kinase (CK) was normal at 170 IU/l in the third trimester. After delivery, hyperCKemia reappeared (715-2620) while her baby tested normal for CK. This is the first report of idiopathic hyperCKemia associated normalization of serum CK level during pregnancy, which has been reported in carriers of Duchenne muscular dystrophy.

A

    34-year-old
    AGE

 previously healthy

    woman
    GENDER

 with

    no remarkable family history
    NEG_FINDINGS

 developed

    asymptomatic hyperCKemia
    BIOCHEMICAL

 at

    age 26
    AGE

. Over the next 6 years,

    hyperCKemia persisted (502-2562 IU/l; normal range<180)
    BIOCHEMICAL

. A

    muscle biopsy
    PARACLINICAL

 showed

    minimal nonspecific myopathy
    DIAGNOSIS

.

    Genetic analysis of blood and muscle samples
    PARACLINICAL

 showed

    no abnormality in the dystrophin gene
    NEG_FINDINGS

. At

    age 33
    AGE

,

    she
    GENDER

 became

    pregnant
    MEDICATION

 for the first time and

    serum creatine kinase (CK) was normal at 170 IU/l in the third trimester
    NEG_FINDINGS

. After

    delivery
    MEDICATION

,

    hyperCKemia reappeared (715-2620)
    BIOCHEMICAL

 while

    her baby tested normal for CK
    NEG_FINDINGS

. This is the first report of

    idiopathic hyperCKemia
    BIOCHEMICAL

 associated

    normalization of serum CK level
    BIOCHEMICAL

 during

    pregnancy
    DIAGNOSIS

, which has been reported in carriers of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

minimal nonspecific myopathy
pregnancy
Duchenne muscular dystrophy


[Female carrier of Duchenne muscular dystrophy presenting with secondary dilated cardiomyopathy: a case report].

A 48-year-old female carrier of Duchenne muscular dystrophy had developed congestive heart failure but had no skeletal muscle symptoms. She was admitted to our hospital complaining of palpitation in December 1998. Her three sons had Duchenne muscular dystrophy. Neurological examination was unremarkable with no evidence of muscle weakness. Serum creatine kinase level was slightly increased. Echocardiography showed severe left ventricular dysfunction. Coronary angiography showed no abnormalities. Left ventriculography showed generalized hypokinesis and left ventricular ejection fraction was 28%. Dystrophin immunostaining of the skeletal muscle biopsy specimen showed a mosaic pattern. The dystrophin negative fibers were scattered among positive fibers. Cardiomyopathy is the only clinical manifestation of dystrophin gene mutation in carriers. Beta-blocker therapy(carvedilol 5 mg/day) was effective in this patient.

A

    48-year-old
    AGE

    female
    GENDER

 carrier of

    Duchenne muscular dystrophy
    DIAGNOSIS

 had developed

    congestive heart failure
    SYMPTOMS

 but had

    no skeletal muscle symptoms
    NEG_FINDINGS

.

    She
    GENDER

 was admitted to our hospital complaining of

    palpitation
    SYMPTOMS

 in December 1998.

    Her three sons had Duchenne muscular dystrophy
    FAMILY

.

    Neurological examination was unremarkable
    NEG_FINDINGS

 with

    no evidence of muscle weakness
    NEG_FINDINGS

.

    Serum creatine kinase level was slightly increased
    BIOCHEMICAL

.

    Echocardiography
    PARACLINICAL

 showed

    severe left ventricular dysfunction
    SYMPTOMS

.

    Coronary angiography showed no abnormalities
    NEG_FINDINGS

.

    Left ventriculography
    PARACLINICAL

 showed

    generalized hypokinesis
    SYMPTOMS

 and

    left ventricular ejection fraction was 28%
    SYMPTOMS

.

    Dystrophin immunostaining of the skeletal muscle biopsy specimen
    PARACLINICAL

 showed a

    mosaic pattern
    MICROSCOPIC

.

    The dystrophin negative fibers were scattered among positive fibers
    MICROSCOPIC

.

    Cardiomyopathy
    DIAGNOSIS

 is the only clinical manifestation of

    dystrophin gene mutation
    GENETICS

 in carriers.

    Beta-blocker therapy(carvedilol 5 mg/day)
    MEDICATION

 was effective in this patient.

Duchenne muscular dystrophy
Cardiomyopathy


Alpha-sarcoglycanopathy previously misdiagnosed as Duchenne muscular dystrophy: implications for current diagnostics and patient care.

Differential diagnosis of limb-girdle muscular dystrophy, including alpha-sarcoglycanopathy and Duchenne muscular dystrophy, is impossible to acheive on clinical grounds alone; therefore immunohistology, Western blotting and molecular genetic analysis are manadatory for a correct diagnosis. The patient's genotype with a hitherto unknown mutation (Tyr134STOP) in exon 5 adds to the growing spectrum of mutations in the alpha-sarcoglycan gene.

    Differential diagnosis
    PARACLINICAL

 of

    limb-girdle muscular dystrophy
    DIAGNOSIS

, including

    alpha-sarcoglycanopathy
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

, is impossible to acheive on clinical grounds alone; therefore

    immunohistology
    PARACLINICAL

,

    Western blotting
    PARACLINICAL

 and

    molecular genetic analysis
    PARACLINICAL

 are manadatory for a correct diagnosis. The patient's

    genotype with a hitherto unknown mutation (Tyr134STOP) in exon 5
    GENETICS

 adds to the growing spectrum of

    mutations in the alpha-sarcoglycan gene
    GENETICS

.

limb-girdle muscular dystrophy
alpha-sarcoglycanopathy
Duchenne muscular dystrophy


Distinguishing cardiac features of a novel form of congenital muscular dystrophy (Salih cmd).

The cardiac features of a novel form of congenital muscular dystrophy (Salih CMD) are described in two adolescent siblings. The patients presented with severe hypotonia at birth, associated with delayed development. They could walk independently and managed to maintain walking after 13 years of age. Their muscle immunohistochemistry differed from that seen in Duchenne and Becher muscular dystrophy (DMD and BMD), severe childhood autosomal recessive muscular dystrophy (SCARMD) due to sarcoglycan deficiency (sarcoglycanopathies), and lamininalpha2 (merosin)-deficient CMD. However, both patients had associated cardiomyopathy. Electrocardiography (ECG) in Salih CMD was characterized by delayed atrioventricular (AV) conduction, left anterior fascicular block (left axis deviation), and left atrial enlargement without evidence of atrial dysarrhythmia. Echocardiography showed features of severe left ventricular dysfunction with estimated left ventricle ejection fraction (LVEF) of 25% at 16 years-of-age in the older patient. A year later, multigated aquisition MUGA scan showed LVEF of 21% and dilatation of the right ventricle. Echocardiography and MUGA scan were normal in the younger patient at 15 years-of-age. ECG, echocardiography, and MUGA scan are effective techniques for diagnosing and monitoring the cardiomyopathy in Salih CMD. They can also distinguish it from features seen in the other common forms of MD, including DMD, BMD, and sarcoglycanopathies.

The

    cardiac features
    SYMPTOMS

 of a

    novel form of congenital muscular dystrophy (Salih CMD)
    DIAGNOSIS

 are described in two

    adolescent
    AGE

 siblings. The patients presented with

    severe hypotonia
    SYMPTOMS

 at

    birth
    AGE

, associated with

    delayed development
    SYMPTOMS

. They

    could walk independently
    SYMPTOMS

 and

    managed to maintain walking
    MEDICATION

    after 13 years of age
    AGE

. Their

    muscle immunohistochemistry
    SYMPTOMS

 differed from that seen in

    Duchenne and Becher muscular dystrophy (DMD and BMD)
    DIAGNOSIS

,

    severe childhood autosomal recessive muscular dystrophy (SCARMD)
    DIAGNOSIS

 due to

    sarcoglycan deficiency (sarcoglycanopathies)
    DIAGNOSIS

, and

    lamininalpha2 (merosin)-deficient CMD
    BIOCHEMICAL

. However, both patients had associated

    cardiomyopathy
    SYMPTOMS

.

    Electrocardiography (ECG)
    PARACLINICAL

 in

    Salih CMD
    DIAGNOSIS

 was characterized by

    delayed atrioventricular (AV) conduction
    SYMPTOMS

,

    left anterior fascicular block (left axis deviation)
    SYMPTOMS

, and

    left atrial enlargement
    SYMPTOMS

    without evidence of atrial dysarrhythmia
    NEG_FINDINGS

.

    Echocardiography
    PARACLINICAL

 showed features of

    severe left ventricular dysfunction
    SYMPTOMS

 with

    estimated left ventricle ejection fraction (LVEF) of 25%
    SYMPTOMS

 at

    16 years-of-age
    AGE

 in the older patient. A year later,

    multigated aquisition MUGA scan
    PARACLINICAL

 showed

    LVEF of 21%
    SYMPTOMS

 and

    dilatation of the right ventricle
    SYMPTOMS

.

    Echocardiography and MUGA scan were normal
    NEG_FINDINGS

 in the younger patient

    at 15 years-of-age
    AGE

.

    ECG
    PARACLINICAL

,

    echocardiography
    PARACLINICAL

, and

    MUGA scan
    PARACLINICAL

 are effective techniques for diagnosing and monitoring the

    cardiomyopathy
    DIAGNOSIS

 in

    Salih CMD
    DIAGNOSIS

. They can also distinguish it from features seen in the other common forms of

    MD
    DIAGNOSIS

, including

    DMD
    DIAGNOSIS

,

    BMD
    DIAGNOSIS

, and

    sarcoglycanopathies
    DIAGNOSIS

.


Abnormality of the myocardial sympathetic nervous system in a patient with Becker muscular dystrophy detected with iodine-123 metaiodobenzylguanidine scintigraphy.

This study was performed to determine whether I-123 metaiodobenzylguanidine (MIBG) scintigraphy can depict myocardial sympathetic nerve abnormalities in Becker muscular dystrophy.

A 34-year-old man with Becker muscular dystrophy underwent Tl-201 and I-123 MIBG scintigraphy sequentially before and 4 months after the beginning of oral administration of enalapril maleate, an angiotensin-converting enzyme inhibitor.

Before and during treatment, stress Tl-201 scintigraphy revealed nonreversible myocardial perfusion defects in the anterior, inferoposterior, and apical walls, and I-123 MIBG scintigraphy depicted a region with decreased sympathetic nerve function or innervation. Before treatment, the I-123 MIBG heart count- mediastinum count (H:M) ratio was 2.1 and the washout rate was 21% on delayed images obtained 4 hours after the injection of I-123 MIBG, indicating hyperactivity of the sympathetic nervous system in the myocardium. During treatment, the H:M ratio was 3.0 and the washout rate was 15%.

With I-123 MIBG scintigraphy it is possible to evaluate an abnormality of the myocardial sympathetic nervous system and the efficacy of administration of an angiotensin-converting enzyme inhibitor in this disease.

This study was performed to determine whether

    I-123 metaiodobenzylguanidine (MIBG) scintigraphy
    PARACLINICAL

 can depict

    myocardial sympathetic nerve abnormalities
    SYMPTOMS

 in

    Becker muscular dystrophy
    DIAGNOSIS

.

A

    34-year-old
    AGE

    man
    GENDER

 with

    Becker muscular dystrophy
    DIAGNOSIS

 underwent

    Tl-201 and I-123 MIBG scintigraphy
    PARACLINICAL

 sequentially before and 4 months after the beginning of

    oral administration of enalapril maleate, an angiotensin-converting enzyme inhibitor
    MEDICATION

.

Before and during treatment,

    stress Tl-201 scintigraphy
    PARACLINICAL

 revealed

    nonreversible myocardial perfusion defects in the anterior, inferoposterior, and apical walls
    SYMPTOMS

, and

    I-123 MIBG scintigraphy
    PARACLINICAL

 depicted a

    region with decreased sympathetic nerve function or innervation
    SYMPTOMS

. Before treatment, the

    I-123 MIBG heart count- mediastinum count (H:M) ratio was 2.1
    PARACLINICAL

 and the

    washout rate was 21% on delayed images obtained 4 hours after the injection of I-123 MIBG
    SYMPTOMS

, indicating

    hyperactivity of the sympathetic nervous system in the myocardium
    SYMPTOMS

. During treatment, the

    H:M ratio was 3.0
    BIOCHEMICAL

 and the

    washout rate was 15%
    SYMPTOMS

.

With

    I-123 MIBG scintigraphy
    PARACLINICAL

 it is possible to evaluate an

    abnormality of the myocardial sympathetic nervous system
    SYMPTOMS

 and the efficacy of

    administration of an angiotensin-converting enzyme inhibitor
    MEDICATION

 in this disease.

Becker muscular dystrophy
Becker muscular dystrophy


Cardiomyopathy in a carrier of Duchenne's muscular dystrophy.

During the third trimester of her pregnancy, a 25-year-old carrier of Duchenne's muscular dystrophy developed severe cardiac failure and required mechanical circulatory support and transplantation. Her cardiac function improved during 311 days of circulatory support. However this improvement was not sufficient to allow removal of her left ventricular assist device before transplantation.

During the

    third trimester of her pregnancy
    AGE

, a

    25-year-old
    AGE

 carrier of

    Duchenne's muscular dystrophy
    DIAGNOSIS

 developed

    severe cardiac failure
    SYMPTOMS

 and required

    mechanical circulatory support
    MEDICATION

 and

    transplantation
    MEDICATION

.

    Her
    GENDER

    cardiac function improved
    SYMPTOMS

 during

    311 days of circulatory support
    MEDICATION

. However this

    improvement was not sufficient to allow removal of her left ventricular assist device before transplantation
    NEG_FINDINGS

.

severe cardiac failure
cardiac function improved

mechanical circulatory support
transplantation
311 days of circulatory support


"Liver function tests" are not always tests of liver function.

A child with Wilm's tumor and a child with immune thrombocytopenic purpura (ITP) were each noted to have persistent elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). Both children underwent thorough evaluation for liver disease and, as a result, experienced delays in treatment of the Wilm's tumor and ITP. Eventually both children were found to have extremely elevated serum creatine kinase (CK). Muscle biopsy confirmed diagnoses of Duchenne's muscular dystrophy in one child, and Becker's muscular dystrophy in the second. Hematologists/oncologists should consider obtaining a serum CK to rule out muscle disease in patients with unexplained elevations of AST, ALT, and LDH.

A

    child
    AGE

 with

    Wilm's tumor
    DIAGNOSIS

 and a

    child
    AGE

 with

    immune thrombocytopenic purpura (ITP)
    DIAGNOSIS

 were each noted to have

    persistent elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH)
    BIOCHEMICAL

. Both

    children
    GENDER

 underwent thorough evaluation for

    liver disease
    DIAGNOSIS

 and, as a result, experienced delays in treatment of the

    Wilm's tumor
    DIAGNOSIS

 and

    ITP
    DIAGNOSIS

. Eventually both

    children
    AGE

 were found to have

    extremely elevated serum creatine kinase (CK)
    BIOCHEMICAL

.

    Muscle biopsy
    PARACLINICAL

 confirmed diagnoses of

    Duchenne's muscular dystrophy
    DIAGNOSIS

 in one child, and

    Becker's muscular dystrophy
    DIAGNOSIS

 in the second.

    Hematologists/oncologists
    PARACLINICAL

 should consider obtaining a

    serum CK
    PARACLINICAL

 to rule out

    muscle disease
    DIAGNOSIS

 in patients with

    unexplained elevations of AST, ALT, and LDH
    BIOCHEMICAL

.

Wilm's tumor
immune thrombocytopenic purpura (ITP)
liver disease
Wilm's tumor
ITP
Duchenne's muscular dystrophy
Becker's muscular dystrophy
muscle disease


Pseudo-metabolic presentation in a Duchenne muscular dystrophy symptomatic carrier with 'de novo' duplication of dystrophin gene.

We report a 6-year-old female patient presenting with a sudden and severe single episode of rhabdomyolysis in which screening for a metabolic disorder was negative. Four months after the episode a muscle biopsy was performed and showed a mild pattern of necrosis/regeneration. Upon immunofluorescence, a mosaic pattern of dystrophin deficiency was found, and in the dystrophin deficient muscle fibres, the four proteins of the sarcoglycan complex were also lacking. Genetic analysis showed a duplication of exons 3 to 17 on one X-chromosome of the proband, but not on the mother's X-chromosome. A clearly skewed X-inactivation (85% of the defective X being active) was found and is consistent with the patient being symptomatic. To our knowledge, a spontaneous rhabdomyolysis in a female Duchenne muscular dystrophy carrier has never been reported.

We report a

    6-year-old
    AGE

    female
    GENDER

 patient presenting with a

    sudden and severe single episode of rhabdomyolysis
    SYMPTOMS

 in which

    screening for a metabolic disorder was negative
    NEG_FINDINGS

. Four months after the episode a

    muscle biopsy
    PARACLINICAL

 was performed and showed a

    mild pattern of necrosis/regeneration
    MICROSCOPIC

. Upon

    immunofluorescence
    PARACLINICAL

, a

    mosaic pattern of dystrophin deficiency
    MICROSCOPIC

 was found, and

    in the dystrophin deficient muscle fibres, the four proteins of the sarcoglycan complex were also lacking
    MICROSCOPIC

.

    Genetic analysis
    PARACLINICAL

 showed

    a duplication of exons 3 to 17 on one X-chromosome of the proband, but not on the mother's X-chromosome
    GENETICS

. A

    clearly skewed X-inactivation (85% of the defective X being active)
    GENETICS

 was found and is consistent with the patient being symptomatic. To our knowledge, a

    spontaneous rhabdomyolysis
    DIAGNOSIS

 in a

    female
    GENDER

    Duchenne muscular dystrophy
    DIAGNOSIS

 carrier has never been reported.

spontaneous rhabdomyolysis
Duchenne muscular dystrophy


Dilated cardiomyopathy of Becker-type muscular dystrophy with exon 4 deletion--a case report.

The authors report a 47-year-old man with Becker-type muscular dystrophy presenting with dilated cardiomyopathy. Left ventriculography showed diffuse severe hypokinesia: left ventricular end-diastolic volume index 193 mL/m2, left ventricular end-systolic volume index 143 mL/m2, and left ventricular ejection fraction 26%. Skeletal muscle biopsy demonstrated a dystrophic process. Genetic analysis revealed a deletion of exon 4. There was a difference in immunostaining pattern between skeletal muscles and cardiac muscles. Severe cardiac dysfunction in this case may be associated with the damage in dystrophin-deficient fibers.

The authors report a

    47-year-old
    AGE

    man
    GENDER

 with

    Becker-type muscular dystrophy
    DIAGNOSIS

 presenting with

    dilated cardiomyopathy
    SYMPTOMS

.

    Left ventriculography
    PARACLINICAL

 showed

    diffuse severe hypokinesia
    SYMPTOMS

:

    left ventricular end-diastolic volume index 193 mL/m2
    SYMPTOMS

,

    left ventricular end-systolic volume index 143 mL/m2
    SYMPTOMS

, and

    left ventricular ejection fraction 26%
    SYMPTOMS

.

    Skeletal muscle biopsy
    PARACLINICAL

 demonstrated a

    dystrophic process
    DIAGNOSIS

.

    Genetic analysis
    PARACLINICAL

 revealed a

    deletion of exon 4
    GENETICS

. There was a

    difference in immunostaining pattern between skeletal muscles and cardiac muscles
    SYMPTOMS

.

    Severe cardiac dysfunction
    SYMPTOMS

 in this case may be associated with the

    damage in dystrophin-deficient fibers
    MICROSCOPIC

.

Becker-type muscular dystrophy
dystrophic process


Effective growth hormone therapy in a growth hormone deficient patient with Duchenne muscular dystropy without evidence of acceleration of the dystrophic process.

We describe a patient with Duchenne muscular dystropy and growth hormone deficiency in whom treatment with human growth hormone for 2 years resulted in improved growth velocity without any detrimental effect on muscle strength.

We describe a patient with

    Duchenne muscular dystropy
    DIAGNOSIS

 and

    growth hormone deficiency
    BIOCHEMICAL

 in whom

    treatment with human growth hormone for 2 years
    MEDICATION

 resulted in

    improved growth velocity
    SYMPTOMS

    without any detrimental effect on muscle strength
    NEG_FINDINGS

.


Limb girdle muscular dystrophy type 2A presenting with cardiac arrest.

The occurrence of respiratory failure in progressive neuromuscular disorders is well recognized. This failure is observed most commonly in Duchenne dystrophy but sometimes occurs in Becker's, limb-girdle, and facioscapulohumeral dystrophies. Patients usually present acutely or subacutely with cyanosis and cor pulmonale, with severe decompensation often being precipitated by an acute intercurrent infection. However, cardiopulmonary arrest is an uncommon presentation. A male diagnosed with limb-girdle muscular dystrophy type 2A who presented with cardiopulmonary arrest that was precipitated by an upper respiratory tract infection is presented. The nocturnal application of noninvasive intermittent positive pressure ventilation with a bilevel positive airway pressure (Bi-PAP) device improved his symptoms and quality of life without resorting to more-invasive and more-restrictive forms of support. This report demonstrates an unusual presentation of limb-girdle muscular dystrophy and documents that nocturnal nasal administration of continuous airway pressure using the Bi-PAP device may be sufficient to maintain adequate ventilation in such patients.

The occurrence of

    respiratory failure
    SYMPTOMS

 in

    progressive neuromuscular disorders
    DIAGNOSIS

 is well recognized. This failure is observed most commonly in

    Duchenne dystrophy
    DIAGNOSIS

 but sometimes occurs in

    Becker's
    DIAGNOSIS

,

    limb-girdle
    DIAGNOSIS

, and

    facioscapulohumeral dystrophies
    DIAGNOSIS

. Patients usually present acutely or subacutely with

    cyanosis
    SYMPTOMS

 and

    cor pulmonale
    SYMPTOMS

, with

    severe decompensation
    SYMPTOMS

 often being precipitated by an

    acute intercurrent infection
    SYMPTOMS

. However,

    cardiopulmonary arrest
    SYMPTOMS

 is an uncommon presentation. A

    male
    GENDER

 diagnosed with

    limb-girdle muscular dystrophy type 2A
    DIAGNOSIS

 who presented with

    cardiopulmonary arrest
    SYMPTOMS

 that was precipitated by an

    upper respiratory tract infection
    SYMPTOMS

 is presented. The

    nocturnal application of noninvasive intermittent positive pressure ventilation with a bilevel positive airway pressure (Bi-PAP) device
    MEDICATION

 improved his

    symptoms and quality of life
    SYMPTOMS

    without resorting to more-invasive and more-restrictive forms of support
    NEG_FINDINGS

. This report demonstrates an unusual presentation of

    limb-girdle muscular dystrophy
    DIAGNOSIS

 and documents that

    nocturnal nasal administration of continuous airway pressure using the Bi-PAP device
    MEDICATION

 may be sufficient to

    maintain adequate ventilation
    MEDICATION

 in such patients.

respiratory failure
cyanosis
cor pulmonale
severe decompensation
acute intercurrent infection
cardiopulmonary arrest
cardiopulmonary arrest
upper respiratory tract infection
symptoms and quality of life

progressive neuromuscular disorders
Duchenne dystrophy
Becker's
limb-girdle
facioscapulohumeral dystrophies
limb-girdle muscular dystrophy type 2A
limb-girdle muscular dystrophy


Total intravenous anaesthesia without muscle relaxants in a child with diagnosed Duchenne muscular dystrophy.

The case of a 3 year old child, affected by Duchenne muscular dystrophy, who underwent adenoidectomy and bilateral myringotomy, is reported. Total intravenous anaesthesia (propofol 1% infusion (160 micrograms kg-1min-1) and remifentanil (0.55 microgram kg-1min-1) without any muscle relaxants was used. The postoperative period was uneventful.

The case of a

    3 year old
    AGE

    child
    AGE

, affected by

    Duchenne muscular dystrophy
    DIAGNOSIS

, who underwent

    adenoidectomy
    MEDICATION

 and

    bilateral myringotomy
    MEDICATION

, is reported.

    Total intravenous anaesthesia (propofol 1% infusion (160 micrograms kg-1min-1) and remifentanil (0.55 microgram kg-1min-1)
    MEDICATION

    without any muscle relaxants
    NEG_FINDINGS

 was used. The postoperative period was uneventful.


Early symptoms of Duchenne muscular dystrophy--description of cases of an 18-month-old and an 8-year-old patient.

The paper presents the description of Duchenne progressive muscular dystrophy in an 18-month-old and an 8-year-old boy. The diagnosis was established on the basis of clinical symptoms, such as impaired motor development, hypertrophy of leg muscles, difficulty in walking; elevated serum phosphocreatine kinase activity and pathologic electromyographic recordings. The authors emphasize that the disease is characterized by increased activity of such enzymes as: alanine and aspartate aminotransferases, lactate dehydrogenase and aldolase--observed as early as in the first weeks of life, with normal gammaglutamyltranspeptidase activity suggests progressive muscular dystrophy and makes it possible to establish early diagnosis. Early diagnosis of the disease allows to start rehabilitation earlier, to select an appropriate type of anesthesia in case of surgical treatment and to advise parents within the framework of genetic counseling.

The paper presents the description of

    Duchenne progressive muscular dystrophy
    DIAGNOSIS

 in an

    18-month-old
    AGE

 and an

    8-year-old
    AGE

    boy
    GENDER

. The diagnosis was established on the basis of clinical symptoms, such as

    impaired motor development
    SYMPTOMS

,

    hypertrophy of leg muscles
    SYMPTOMS

,

    difficulty in walking
    SYMPTOMS

;

    elevated serum phosphocreatine kinase activity
    BIOCHEMICAL

 and

    pathologic electromyographic recordings
    SYMPTOMS

. The authors emphasize that the disease is characterized by

    increased activity of such enzymes as: alanine and aspartate aminotransferases, lactate dehydrogenase and aldolase--
    BIOCHEMICAL

observed as

    early as in the first weeks of life
    AGE

, with

    normal gammaglutamyltranspeptidase activity
    NEG_FINDINGS

 suggests

    progressive muscular dystrophy
    DIAGNOSIS

 and makes it possible to establish early diagnosis. Early diagnosis of the disease allows to start

    rehabilitation earlier
    MEDICATION

, to select an

    appropriate type of anesthesia
    MEDICATION

 in case of

    surgical treatment
    MEDICATION

 and to advise parents within the framework of

    genetic counseling
    MEDICATION

.

Duchenne progressive muscular dystrophy
progressive muscular dystrophy

impaired motor development
hypertrophy of leg muscles
difficulty in walking
pathologic electromyographic recordings

rehabilitation earlier
appropriate type of anesthesia
surgical treatment
genetic counseling


Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy.

A 43 year old male presented with slowly progressive weakness of limbs and hypertrophy of triceps, brachioradialis and calf muscles for four years. There was thinning of quadriceps muscles in both thighs. Histological study was compatible with Becker muscular dystrophy (BMD). Genomic DNA analysis showed a deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters. The clinical and laboratory characteristics in this patient are in keeping with what has been described 'quadriceps myopathy' and fall within the phenotypic variants of BMD as has been shown by others.

A

    43 year old
    AGE

    male
    GENDER

 presented with

    slowly progressive weakness of limbs
    SYMPTOMS

 and

    hypertrophy of triceps, brachioradialis and calf muscles
    SYMPTOMS

    for four years
    SYMPTOMS

. There was

    thinning of quadriceps muscles in both thighs
    SYMPTOMS

.

    Histological study
    PARACLINICAL

 was compatible with

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

.

    Genomic DNA analysis
    PARACLINICAL

 showed a

    deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters
    GENETICS

. The clinical and laboratory characteristics in this patient are in keeping with what has been described '

    quadriceps myopathy
    DIAGNOSIS

' and fall within the phenotypic variants of

    BMD
    DIAGNOSIS

 as has been shown by others.

Becker muscular dystrophy (BMD)
quadriceps myopathy
BMD


Becker muscular dystrophy associated with focal myositis on bone scintigraphy.

Bone scintigraphy was performed on a 6-year-old boy with possible sacroiliitis.

Extraosseous uptake in the region of the paraspinal, psoas and calf muscles was noted and suggested myositis. Subsequently, his creatine kinase level was found to be elevated. Results of a neuromuscular examination, muscle biopsy with dystrophin immunostaining, and a multiplex polymerase chain reaction led to the diagnosis of Becker muscular dystrophy.

A patient with Becker muscular dystrophy had several distinct areas of myositis localized by bone scintigraphy. Pathologic features including focal myonecrosis and regeneration may contribute to this scintigraphic picture.

    Bone scintigraphy
    PARACLINICAL

 was performed on a

    6-year-old
    AGE

    boy
    GENDER

 with possible

    sacroiliitis
    DIAGNOSIS

.

    Extraosseous uptake in the region of the paraspinal, psoas and calf muscles
    SYMPTOMS

 was noted and suggested

    myositis
    DIAGNOSIS

. Subsequently,

    his
    GENDER

    creatine kinase level
    BIOCHEMICAL

 was found

    to be elevated
    BIOCHEMICAL

. Results of a

    neuromuscular examination
    PARACLINICAL

,

    muscle biopsy
    PARACLINICAL

 with

    dystrophin immunostaining
    PARACLINICAL

, and a

    multiplex polymerase chain reaction
    PARACLINICAL

 led to the diagnosis of

    Becker muscular dystrophy
    DIAGNOSIS

.

A patient with

    Becker muscular dystrophy
    DIAGNOSIS

 had

    several distinct areas of myositis
    SYMPTOMS

 localized by

    bone scintigraphy
    PARACLINICAL

. Pathologic features including

    focal myonecrosis
    MICROSCOPIC

 and

    regeneration
    SYMPTOMS

 may contribute to this

    scintigraphic
    PARACLINICAL

 picture.

sacroiliitis
myositis
Becker muscular dystrophy
Becker muscular dystrophy


[Acute gastric dilatation in Duchenne's muscular dystrophy].

A 15 year old boy with Duchenne muscular dystrophy had severe pain in the lower abdomen and complained of nausea and bilious vomiting. A physical examination and an abdominal X-ray indicated an acute gastric dilation. With a treatment policy of administering nothing orally, a downward-hanging stomach tube and the intravenous administration of fluid the symptoms subsided. In Duchenne muscular dystrophy there may also be atrophy of the smooth muscle layers, in addition to the known progressive atrophy of striated skeletal and cardiac muscle. This may cause clinical dysfunctioning of the gastro-intestinal tract in the second decade of life.

A

    15 year old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 had

    severe pain in the lower abdomen
    SYMPTOMS

 and complained of

    nausea
    SYMPTOMS

 and

    bilious vomiting
    SYMPTOMS

. A

    physical examination
    PARACLINICAL

 and an

    abdominal X-ray
    PARACLINICAL

 indicated an

    acute gastric dilation
    SYMPTOMS

. With a treatment policy of

    administering nothing orally, a downward-hanging stomach tube
    MEDICATION

 and the

    intravenous administration of fluid
    MEDICATION

 the symptoms subsided. In

    Duchenne muscular dystrophy
    DIAGNOSIS

 there may also be

    atrophy of the smooth muscle layers
    SYMPTOMS

, in addition to the known

    progressive atrophy of striated skeletal and cardiac muscle
    SYMPTOMS

. This may cause

    clinical dysfunctioning of the gastro-intestinal tract
    SYMPTOMS

 in the

    second decade of life
    AGE

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy


[The heartache of muscular dystrophy].

Duchenne and Becker muscular dystrophy are caused by a mutation in the dystrophin gene, located on the short arm of the X chromosome. Three so called dystrophinopathy patients, a women aged 54 and two men aged 23 and 21 years, suffered from a severe dilated cardiomyopathy. Such a cardiomyopathy can develop in both carriers and patients. In addition, it is often more important for prognosis than muscle weakness. For these two reasons it is important to screen both groups for (early) cardiological abnormalities. If these are present, regular follow-up is necessary to start timely therapy. When cardiological investigations yield normal results, it is advised to screen carriers with a five-year interval. Dystrophinopathy patients should be checked every year, because the cardiomyopathy sometimes develops and deteriorates over a short period of time. Patients with dilated cardiomyopathy and with a positive family history for dilated cardiomyopathy, muscle weakness or high serum creatine kinase activity should be screened for a mutation in the dystrophin gene.

    Duchenne
    DIAGNOSIS

 and

    Becker muscular dystrophy
    DIAGNOSIS

 are caused by a

    mutation in the dystrophin gene, located on the short arm of the X chromosome
    GENETICS

. Three so called

    dystrophinopathy
    DIAGNOSIS

 patients, a

    women
    GENDER

    aged 54
    AGE

 and two

    men
    GENDER

    aged 23 and 21 years
    AGE

, suffered from a

    severe dilated cardiomyopathy
    DIAGNOSIS

. Such a

    cardiomyopathy
    DIAGNOSIS

 can develop in both carriers and patients. In addition, it is often more important for prognosis than

    muscle weakness
    SYMPTOMS

. For these two reasons it is important to screen both groups for (early)

    cardiological abnormalities
    SYMPTOMS

. If these are present,

    regular follow-up
    PARACLINICAL

 is necessary to start

    timely therapy
    MEDICATION

. When

    cardiological investigations yield normal results
    NEG_FINDINGS

, it is advised to screen carriers with a five-year interval.

    Dystrophinopathy
    DIAGNOSIS

 patients should be checked every year, because the

    cardiomyopathy
    SYMPTOMS

 sometimes develops and deteriorates over a short period of time. Patients with

    dilated cardiomyopathy
    SYMPTOMS

 and with a

    positive family history for dilated cardiomyopathy
    FAMILY

,

    muscle weakness
    SYMPTOMS

 or

    high serum creatine kinase activity
    BIOCHEMICAL

 should be screened for a

    mutation in the dystrophin gene
    GENETICS

.

Duchenne
Becker muscular dystrophy
dystrophinopathy
severe dilated cardiomyopathy
cardiomyopathy
Dystrophinopathy

muscle weakness
cardiological abnormalities
cardiomyopathy
dilated cardiomyopathy
muscle weakness


Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy.

Myogenic factors (MYF) belong to the basic helix-loop-helix (bHLH) transcription factor family and regulate myogenesis and muscle regeneration. The physiological importance of both functions was demonstrated in homozygous Myf knockout mice and mdx mice. Myf5 and Myod are predominantly expressed in proliferating myoblasts while Myf4 and Myf6 are involved in differentiation of myotubes. In a boy with myopathy and an increase of muscle fibres with central nuclei we detected a heterozygous 387G-->T nucleotide transversion in the MYF6 gene (MIM*159991). Protein-protein interaction of mutant MYF6 was reduced, and DNA-binding potential and transactivation capacity were abolished, thus demonstrating MYF6 haploinsufficiency. The boy's father carried the identical mutation and, in addition, an in-frame deletion of exons 45-47 in his dystrophin gene. This mutation is normally associated with a mild to moderate course of Becker muscular dystrophy but the father suffered from a severe course of Becker muscular dystrophy suggesting MYF6 as a modifier.

    Myogenic factors (MYF)
    GENETICS

 belong to the

    basic helix-loop-helix (bHLH) transcription factor family
    GENETICS

 and regulate

    myogenesis
    SYMPTOMS

 and

    muscle regeneration
    SYMPTOMS

. The physiological importance of both functions was demonstrated in

    homozygous Myf
    GENETICS

 knockout mice and mdx mice.

    Myf5 and Myod
    GENETICS

 are predominantly expressed in

    proliferating myoblasts
    MICROSCOPIC

 while

    Myf4
    GENETICS

 and

    Myf6
    GENETICS

 are involved in

    differentiation of myotubes
    MICROSCOPIC

. In a

    boy
    GENDER

 with

    myopathy
    DIAGNOSIS

 and an

    increase of muscle fibres with central nuclei
    MICROSCOPIC

 we detected a

    heterozygous 387G-->T nucleotide transversion in the MYF6 gene (MIM*159991)
    GENETICS

.

    Protein-protein interaction of mutant MYF6 was reduced
    BIOCHEMICAL

, and

    DNA-binding potential and transactivation capacity were abolished
    BIOCHEMICAL

, thus demonstrating

    MYF6 haploinsufficiency
    GENETICS

. The

    boy
    GENDER

    's father carried the identical mutation and, in addition, an in-frame deletion of exons 45-47 in his dystrophin gene
    FAMILY

. This mutation is normally associated with a

    mild to moderate course of Becker muscular dystrophy
    DIAGNOSIS

 but

    the father suffered from a severe course of Becker muscular dystrophy
    FAMILY

 suggesting

    MYF6
    GENETICS

 as a modifier.


[Post exercise myalgias as presentation form of dystrophinopathy].

Cramps and myalgias are frequent presentations of many disorders whose diagnosis is generally difficult. Among the unusual causes stand the milder phenotypes of dystrophinopathies, which are caused, just as Duchenne and Becker's dystrophy, by mutations in the dystrophin gene. An 8 year-old boy presented severe muscle pain on exercise and serum rise in creatine kinase over 1000 U/l. He had normal muscle power and mild calf hypertrophy. The molecular analysis by polymerase chain reaction (PCR) of the dystrophin gene showed deletions of exons 45 to 51. Dystrophin analysis by Western blot revealed a dystrophin of reduced quantity and molecular weight. Emphasis is made to include dystrophinopathies in the differential diagnosis of myalgias and the usefulness of molecular genetic techniques in the identification of these disorders.

    Cramps
    SYMPTOMS

 and

    myalgias
    SYMPTOMS

 are frequent presentations of many disorders whose diagnosis is generally difficult. Among the unusual causes stand the milder phenotypes of

    dystrophinopathies
    DIAGNOSIS

, which are caused, just as

    Duchenne
    DIAGNOSIS

 and

    Becker's dystrophy
    DIAGNOSIS

, by

    mutations in the dystrophin gene
    GENETICS

. An

    8 year-old
    AGE

    boy
    GENDER

 presented

    severe muscle pain
    SYMPTOMS

 on

    exercise
    SYMPTOMS

 and serum rise in creatine kinase over 1000 U/l.

    He
    GENDER

 had

    normal muscle power
    NEG_FINDINGS

 and

    mild calf hypertrophy
    SYMPTOMS

. The

    molecular analysis by polymerase chain reaction (PCR) of the dystrophin gene
    PARACLINICAL

 showed

    deletions of exons 45 to 51
    GENETICS

.

    Dystrophin analysis by Western blot
    PARACLINICAL

 revealed a

    dystrophin of reduced quantity and molecular weight
    BIOCHEMICAL

. Emphasis is made to include

    dystrophinopathies
    DIAGNOSIS

 in the

    differential diagnosis
    PARACLINICAL

 of

    myalgias
    DIAGNOSIS

 and the usefulness of

    molecular genetic techniques
    PARACLINICAL

 in the identification of these disorders.

Cramps
myalgias
severe muscle pain
exercise
mild calf hypertrophy

dystrophinopathies
Duchenne
Becker's dystrophy
dystrophinopathies
myalgias

mutations in the dystrophin gene
deletions of exons 45 to 51


Dystrophin nonsense mutation induces different levels of exon 29 skipping and leads to variable phenotypes within one BMD family.

Within one X-linked muscular dystrophy family, different phenotypes for three males occurred: (1) a severely affected Becker patient with cardiomyopathy, (2) a mildly affected Becker patient, and (3) an apparently healthy male with elevated serum CK levels. In the muscle biopsy specimen of patient2 one out of four antibodies (NCL-DYS1) showed absence of dystrophin. The protein truncation test detected a truncated dystrophin for both muscle tissue and lymphocytes of this patient next to an additional near normal size fragment in muscle. Genomic sequence analysis revealed a nonsense mutation in exon 29 (4148C > T) of the dystrophin gene. Sequence analysis of the mRNA fragment of the larger peptide showed skipping of exon 29, restoring an open reading frame. Consequently, the epitope of the antibody NCL-DYS1 is mapped to exon 29. The variable clinical features of the three relatives from healthy to severely affected therefore seems to be related to the level of skipping of exon 29. This finding underscores the future potential of gene therapeutic strategies aimed at inducing exon skipping in Duchenne muscular dystrophy, to generate a much milder disease.

Within one

    X-linked
    GENETICS

    muscular dystrophy
    DIAGNOSIS

    family
    FAMILY

, different phenotypes for three

    males
    GENDER

 occurred: (1) a severely affected

    Becker
    DIAGNOSIS

 patient with

    cardiomyopathy
    DIAGNOSIS

, (2) a mildly affected

    Becker
    DIAGNOSIS

 patient, and (3) an apparently healthy

    male
    GENDER

 with

    elevated serum CK levels
    BIOCHEMICAL

. In the

    muscle biopsy specimen
    PARACLINICAL

 of patient2 one out of four

    antibodies (NCL-DYS1)
    BIOCHEMICAL

 showed

    absence of dystrophin
    BIOCHEMICAL

. The

    protein truncation test
    PARACLINICAL

 detected a

    truncated dystrophin for both muscle tissue and lymphocytes
    MICROSCOPIC

 of this patient next to an additional near

    normal size fragment in muscle
    SYMPTOMS

.

    Genomic sequence analysis
    PARACLINICAL

 revealed a

    nonsense mutation in exon 29 (4148C > T) of the dystrophin gene
    GENETICS

.

    Sequence analysis of the mRNA fragment of the larger peptide
    PARACLINICAL

 showed

    skipping of exon 29, restoring an open reading frame
    GENETICS

. Consequently, the epitope of the antibody NCL-DYS1 is mapped to

    exon 29
    GENETICS

. The variable clinical features of the three relatives from healthy to severely affected therefore seems to be related to the

    level of skipping of exon 29
    GENETICS

. This finding underscores the future potential of gene therapeutic strategies aimed at

    inducing exon skipping
    MEDICATION

 in

    Duchenne muscular dystrophy
    DIAGNOSIS

, to generate a much milder disease.

muscular dystrophy
Becker
cardiomyopathy
Becker
Duchenne muscular dystrophy

elevated serum CK levels
antibodies (NCL-DYS1)
absence of dystrophin


Incidental prenatal detection of an Xp deletion using an anonymous primer pair for fetal sexing.

We report on the incidental prenatal detection of an interstitial X-chromosomal deletion in a male fetus and his mother by fetal sexing with a primer pair recognizing an X-Y homologous locus (DXYS19), formerly unassigned on the X chromosome. The proband asked for prenatal diagnosis because of her elevated age and risk of Duchenne muscular dystrophy (DMD). Prior to molecular genetic testing for DMD, fetal sexing was carried out on DNA prepared from cultured amniocytes. PCR analysis revealed the expected Y-chromosomal product, but did not show the constitutive X-chromosomal fragment. The absence of the X-chromosomal fragment in the fetus and on one X chromosome of the mother was confirmed by Southern hybridization of HindIII restricted DNA with probe pJA1165 (DXYS19). DXYS19X was mapped to Xp22.3 by combining several approaches, including: (1) analysis of somatic cell hybrid lines containing different fragments of the human X chromosome; (2) Southern hybridization of a yeast artificial chromosome (YAC)-filter panel provided by the Resource Center/Primary Database (RZPD); (3) FISH analysis; and (4) re-evaluation of two patients with interstitial deletions in Xp22.3. The extent of the deletion in the fetus was estimated by further markers from Xp22.3 and found to include the STS gene. Mental retardation could not be excluded since some mentally retarded patients exhibit overlapping deletions.

We report on the incidental prenatal detection of an

    interstitial X-chromosomal deletion
    GENETICS

 in a

    male
    GENDER

    fetus
    AGE

 and his

    mother
    GENDER

 by

    fetal sexing
    PARACLINICAL

 with a primer pair recognizing an

    X-Y homologous locus (DXYS19), formerly unassigned on the X chromosome
    GENETICS

. The

    proband
    GENDER

 asked for

    prenatal diagnosis
    PARACLINICAL

 because of

    her
    GENDER

    elevated age
    AGE

 and risk of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Prior to

    molecular genetic testing
    PARACLINICAL

 for

    DMD
    DIAGNOSIS

,

    fetal sexing
    PARACLINICAL

 was carried out on

    DNA prepared from cultured amniocytes
    PARACLINICAL

.

    PCR analysis
    PARACLINICAL

 revealed the expected

    Y-chromosomal product
    GENETICS

, but

    did not show the constitutive X-chromosomal fragment
    NEG_FINDINGS

. The

    absence of the X-chromosomal fragment in the fetus and on one X chromosome of the mother
    GENETICS

 was confirmed by

    Southern hybridization of HindIII restricted DNA with probe pJA1165 (DXYS19)
    PARACLINICAL

.

    DXYS19X
    GENETICS

 was mapped to

    Xp22.3
    GENETICS

 by combining several approaches, including: (1)

    analysis of somatic cell hybrid lines containing different fragments of the human X chromosome
    PARACLINICAL

; (2)

    Southern hybridization of a yeast artificial chromosome (YAC)-filter panel
    PARACLINICAL

 provided by the Resource Center/Primary Database (RZPD); (3)

    FISH analysis
    PARACLINICAL

; and (4) re-evaluation of two patients with

    interstitial deletions in Xp22.3
    GENETICS

. The extent of the deletion in the fetus was estimated by

    further markers from Xp22.3
    PARACLINICAL

 and found to include the

    STS gene
    GENETICS

.

    Mental retardation
    DIAGNOSIS

    could not be excluded
    NEG_FINDINGS

 since some

    mentally retarded
    SYMPTOMS

 patients exhibit

    overlapping deletions
    SYMPTOMS

.

Duchenne muscular dystrophy (DMD)
DMD
Mental retardation