[Rare combination of dystrophinopathy and Klinefelter's syndrome in one patient].

To analyze clinical characteristics of a combination of dystrophinopathies and Klinefelter's syndrome (karyotype 47, XXY) in one patient.

The patient was diagnosed as Duchenne muscular dystrophy (DMD) and Klinefelter's syndrome in Beijing Children's Hospital in March, 2013. The clinical manifestations, physical examinations and laboratory test results were analyzed respectively. The clinical characteristics of four cases reported previously were analyzed as well.

The 8.5 years old boy presented with symptoms of walking disorder and developmental delay. The patient had facial dysmorphism, waddling gait, Gower's manoeuvre and enlarged calves.Serum creatine kinase level was 21 040 U/L, and he had mild intellectual impairment. Deletions of exons 49-54 of the dystrophin gene were found.Gene dosage analysis revealed a heterozygous deletion in his mother. Five cases have been reported till now, their age ranged from 3.5 to 18 years; 3 of them were DMD, while the other 2 cases were Becker muscular dystrophy (BMD). One of them, detected in pedigree study, whose weakness was minimal in contrast to the proband. The others came to the hospital because of walking disorder or developmental delay. All the patients had enlarged calves, some of them also had Gower's manoeuvre and waddling gait. The patients' height was between 3 rd and 50 th percentile, while 2 of them had facial dysmorphism.Some degree of mental impairment is usual. Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in pedigree study. Three of them were diagnosed by muscle biopsy, while in the other one mutation analysis was used.

The combination of dystrophinopathies and Klinefelter's syndrome is quite rare, and has clinical features of these two diseases. Mutation analysis (or muscle biopsy) and karyotype analysis can finally diagnose the syndrome.

To analyze clinical characteristics of a

    combination of dystrophinopathies
    DIAGNOSIS

 and

    Klinefelter's syndrome
    DIAGNOSIS

 (

    karyotype 47, XXY)
    GENETICS

 in one patient.

The patient was diagnosed as

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 and

    Klinefelter's syndrome
    DIAGNOSIS

 in Beijing Children's Hospital in March, 2013. The clinical manifestations,

    physical examinations
    PARACLINICAL

 and

    laboratory test results
    PARACLINICAL

 were analyzed respectively. The clinical characteristics of four cases reported previously were analyzed as well.

The

    8.5 years old
    AGE

    boy
    GENDER

 presented with symptoms of

    walking disorder
    SYMPTOMS

 and

    developmental delay
    SYMPTOMS

. The patient had

    facial dysmorphism
    SYMPTOMS

,

    waddling gait
    SYMPTOMS

,

    Gower's manoeuvre
    SYMPTOMS

 and

    enlarged calves
    SYMPTOMS

.

    Serum creatine kinase level was 21 040 U/L
    BIOCHEMICAL

, and

    he
    GENDER

 had

    mild intellectual impairment
    SYMPTOMS

.

    Deletions of exons 49-54 of the dystrophin gene
    GENETICS

 were found.

    Gene dosage analysis
    PARACLINICAL

 revealed a

    heterozygous deletion in his mother
    GENETICS

. Five cases have been reported till now, their

    age ranged from 3.5 to 18 years
    AGE

; 3 of them were

    DMD
    DIAGNOSIS

, while the other 2 cases were

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

. One of them, detected in

    pedigree study
    PARACLINICAL

, whose

    weakness was minimal in contrast to the proband
    SYMPTOMS

. The others came to the hospital because of

    walking disorder
    SYMPTOMS

 or

    developmental delay
    SYMPTOMS

. All the patients had

    enlarged calves
    SYMPTOMS

, some of them also had

    Gower's manoeuvre
    SYMPTOMS

 and

    waddling gait
    SYMPTOMS

. The patients'

    height was between 3 rd and 50 th percentile
    SYMPTOMS

, while 2 of them had

    facial dysmorphism
    SYMPTOMS

.

    Some degree of mental impairment
    SYMPTOMS

 is usual. Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in

    pedigree study
    PARACLINICAL

. Three of them were diagnosed by

    muscle biopsy
    PARACLINICAL

, while in the other one

    mutation analysis
    PARACLINICAL

 was used.

The

    combination of dystrophinopathies
    DIAGNOSIS

    and Klinefelter's syndrome
    DIAGNOSIS

 is quite rare, and has

    clinical features of these two diseases
    SYMPTOMS

.

    Mutation analysis (or muscle biopsy)
    PARACLINICAL

 and

    karyotype analysis
    PARACLINICAL

 can finally diagnose the syndrome.

combination of dystrophinopathies
Klinefelter's syndrome
Duchenne muscular dystrophy (DMD)
Klinefelter's syndrome
DMD
Becker muscular dystrophy (BMD)
combination of dystrophinopathies
and Klinefelter's syndrome


Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy.

A

    54-year-old
    AGE

 patient with

    Becker muscular dystrophy
    DIAGNOSIS

 and

    dilated cardiomyopathy
    DIAGNOSIS

 underwent

    laparoscopic cholecystectomy
    MEDICATION

 under

    total intravenous anesthesia
    MEDICATION

.

    Muscle relaxation
    MEDICATION

 was induced by

    rocuronium (0.4 mg/kg body weight)
    MEDICATION

 under

    train-of-four (TOF) ratio monitoring
    PARACLINICAL

. The

    TOF ratio was 0
    SYMPTOMS

 at intubation, and

    0.2
    SYMPTOMS

 at the end of surgery.

    Residual muscle relaxant activity
    SYMPTOMS

 was successfully

    reversed by sugammadex (2 mg/kg body weight)
    MEDICATION

    without any hemodynamic adverse effects
    NEG_FINDINGS

 (

    TOF ratio 1.0 at extubation)
    SYMPTOMS

. The clinical and hemodynamic findings suggest that

    sugammadex
    MEDICATION

 can be safely used in patients with

    Becker muscular dystrophy
    DIAGNOSIS

 and

    dilated cardiomyopathy
    DIAGNOSIS

.

Becker muscular dystrophy
dilated cardiomyopathy
Becker muscular dystrophy
dilated cardiomyopathy

TOF ratio was 0
0.2
Residual muscle relaxant activity
TOF ratio 1.0 at extubation)


Preimplantational genetic diagnosis and mutation detection in a family with duplication mutation of DMD gene.

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease caused by mutation in the DMD gene. A 38-year-old woman was referred to our hospital with her son who was diagnosed with DMD. Multiplex PCR failed to detect DMD mutations in the affected child. The female carrier underwent preimplantation genetic diagnosis by linkage analysis and gender determination. Eight embryos were biopsied after in vitro fertilization. Two healthy embryos determined both as females (E1 and E3) were transferred. Although the paternal allele was absent in E3, it was considered to be a result of allele dropout for the STR-49 marker. Surprisingly, a female and a male baby were delivered at 38 gestational weeks, suggesting that E3 was a male embryo with the allele dropout occurring at the SRY gene. Exon 2 duplication was detected in the DMD patient and the carrier mother using next-generation sequencing and multiple ligation-dependent probe amplification. Next, we verified the duplication of exon 2 by real-time PCR, using a special primer at 3' of intron 1, very close to exon 2. Finally, we confirmed that both newborns inherited the normal allele, using quantitative real-time PCR and linkage analysis.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked recessive neuromuscular disease
    GENETICS

 caused by

    mutation in the DMD gene
    GENETICS

. A

    38-year-old
    AGE

    woman
    GENDER

 was referred to our hospital with

    her
    GENDER

    son who was diagnosed with DMD
    FAMILY

.

    Multiplex PCR
    PARACLINICAL

    failed to detect DMD mutations in the affected child
    NEG_FINDINGS

. The

    female
    GENDER

 carrier underwent

    preimplantation genetic diagnosis
    MEDICATION

 by

    linkage analysis
    PARACLINICAL

 and

    gender determination
    PARACLINICAL

. Eight embryos were

    biopsied
    PARACLINICAL

 after

    in vitro fertilization
    MEDICATION

. Two healthy embryos determined both as females (E1 and E3) were transferred. Although

    the paternal allele was absent in E3
    GENETICS

, it was considered to be a result of

    allele dropout for the STR-49 marker
    GENETICS

. Surprisingly, a

    female
    GENDER

    and a male baby were delivered at 38 gestational weeks
    MEDICATION

, suggesting that E3 was a

    male
    GENDER

 embryo with the

    allele dropout occurring at the SRY gene
    GENETICS

.

    Exon 2 duplication
    GENETICS

 was detected in the

    DMD
    DIAGNOSIS

 patient and the carrier mother using

    next-generation sequencing and multiple ligation-dependent probe amplification
    PARACLINICAL

. Next, we verified the

    duplication of exon 2
    GENETICS

 by

    real-time PCR
    PARACLINICAL

, using a

    special primer at 3' of intron 1, very close to exon 2
    GENETICS

. Finally, we confirmed that

    both newborns inherited the normal allele
    FAMILY

, using

    quantitative real-time PCR
    PARACLINICAL

 and

    linkage analysis
    PARACLINICAL

.


When a mid-intronic variation of DMD gene creates an ESE site.

Duchenne and Becker muscular dystrophy are X-linked allelic disorders caused by mutations in the DMD gene. The majority (65%) of these mutations are intragenic deletions/duplications that often lead to frameshift errors. Among the remaining ones, we find the mid-intronic mutations that usually create cryptic exons by activating potential splice sites. In this report, we identified, in a Becker muscular dystrophy patient, a mid-intronic variation that creates two ESE sites in intron 26 of DMD gene resulting in the insertion of a new cryptic exon in mRNA. Despite the out of frame character of this mutation, we observed the production of a reduced amount of full-size dystrophin which could be explained by the alternation between normal and altered splicing of dystrophin mRNA in this patient. To our knowledge, this is the first case report describing this novel pathogenic mechanism of mid-intronic variations of DMD gene.

    Duchenne
    DIAGNOSIS

 and

    Becker muscular dystrophy
    DIAGNOSIS

 are

    X-linked allelic disorders
    GENETICS

 caused by

    mutations in the DMD gene
    GENETICS

. The majority (65%) of these mutations are

    intragenic deletions/duplications
    GENETICS

 that often lead to

    frameshift errors
    GENETICS

. Among the remaining ones, we find the

    mid-intronic mutations
    GENETICS

 that usually

    create cryptic exons by activating potential splice sites
    GENETICS

. In this report, we identified, in a

    Becker muscular dystrophy
    DIAGNOSIS

 patient, a

    mid-intronic variation that creates two ESE sites in intron 26 of DMD gene resulting in the insertion of a new cryptic exon in mRNA
    GENETICS

.

    Despite the out of frame character of this mutation
    NEG_FINDINGS

, we observed the production of a

    reduced amount of full-size dystrophin
    BIOCHEMICAL

 which could be explained by the

    alternation between normal and altered splicing of dystrophin mRNA
    GENETICS

 in this patient. To our knowledge, this is the first case report describing this novel pathogenic mechanism of

    mid-intronic variations of DMD gene
    GENETICS

.

Duchenne
Becker muscular dystrophy
Becker muscular dystrophy


Be careful about abdominal discomfort in adult patients with muscular dystrophy.

Muscular dystrophies are genetic muscular disease with disability. Heart failure is a classical complication mainly in Duchenne muscular dystrophy (DMD). We report 2 cases of severe acute heart failure revealed by abdominal discomfort in a patient with DMD and in a patient with gamma-sarcoglycanopathy.

    Muscular dystrophies
    DIAGNOSIS

 are

    genetic muscular disease
    DIAGNOSIS

 with

    disability
    SYMPTOMS

.

    Heart failure
    SYMPTOMS

 is a classical complication mainly in

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. We report 2 cases of

    severe acute heart failure
    SYMPTOMS

 revealed by

    abdominal discomfort
    SYMPTOMS

 in a patient with

    DMD
    DIAGNOSIS

 and in a patient with

    gamma-sarcoglycanopathy
    DIAGNOSIS

.

Muscular dystrophies
genetic muscular disease
Duchenne muscular dystrophy (DMD)
DMD
gamma-sarcoglycanopathy

disability
Heart failure
severe acute heart failure
abdominal discomfort


Complications with utilization of positive-pressure devices in a young man with duchenne muscular dystrophy.

Because of the progressive muscle weakness they experience, patients with Duchenne muscular dystrophy frequently utilize positive-pressure devices to maintain adequate bronchial hygiene and ventilation. This case illustrates the course of a 19-y-old male who presented with a perforated right tympanic membrane (TM) following the use of these devices. Perforation of the TM while utilizing positive-pressure devices is a rarely reported event. A challenging aspect in this case was balancing the reduction of pressures and maintaining adequate ventilation while at the same time allowing the TM to heal.

Because of the

    progressive muscle weakness
    SYMPTOMS

 they experience, patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 frequently utilize

    positive-pressure devices
    MEDICATION

 to

    maintain adequate bronchial hygiene and ventilation
    MEDICATION

. This case illustrates the course of a

    19-y-old
    AGE

    male
    GENDER

 who presented with a

    perforated right tympanic membrane (TM)
    SYMPTOMS

 following the

    use of these devices
    MEDICATION

.

    Perforation of the TM
    SYMPTOMS

 while

    utilizing positive-pressure devices
    MEDICATION

 is a rarely reported event. A challenging aspect in this case was

    balancing the reduction of pressures
    MEDICATION

 and

    maintaining adequate ventilation
    MEDICATION

 while at the same time allowing

    the TM to heal
    SYMPTOMS

.

progressive muscle weakness
perforated right tympanic membrane (TM)
Perforation of the TM
the TM to heal


Positive effects of an angiotensin II type 1 receptor antagonist in Camurati-Engelmann disease: a single case observation.

Camurati-Engelmann disease is characterized by hyperostosis of the long bones and the skull, muscle atrophy, severe limb pain, and progressive joint contractures in some patients. It is caused by heterozygous mutations in the transforming growth factor β1 (TGFβ1) believed to result in improper folding of the latency-associated peptide domain of TGFβ1 and thus in increased or deregulated bioactivity. Losartan, an angiotensin II type 1 receptor antagonist, has been found to downregulate the expression of TGFβ type 1 and 2 receptors. Clinical trials with losartan have shown a benefit in Marfan syndrome, while trials are underway for Duchenne muscular dystrophy and other myopathies associated with TGFβ1 signaling. We hypothesized that due to its anti-TGFβ1 activity, losartan might be beneficial in Camurati-Engelmann disease. This report concerns a boy who presented at age 13 years with severe limb pain and difficulty in walking. Clinical and radiographic evaluation results were compatible with Camurati-Engelmann disease and the diagnosis was confirmed by mutation analysis (c.652C > T [p.Arg218Cys]). The boy underwent an experimental treatment with losartan at a dosage of 50 mg/day, orally. During the treatment period of 18 months, the intensity and frequency of limb pain decreased significantly (as shown by a pain diary), and muscle strength improved, allowing the boy to resume walking and climbing stairs. No obvious side effects were observed. We cautiously conclude that TGFβ1 inhibition with losartan deserves further evaluation in the clinical management of Camurati-Engelmann disease.

    Camurati-Engelmann disease
    DIAGNOSIS

 is characterized by

    hyperostosis of the long bones and the skull
    SYMPTOMS

,

    muscle atrophy
    SYMPTOMS

,

    severe limb pain
    SYMPTOMS

, and

    progressive joint contractures
    SYMPTOMS

 in some patients. It is caused by

    heterozygous mutations in the transforming growth factor β1 (TGFβ1)
    GENETICS

 believed to result in

    improper folding of the latency-associated peptide domain of TGFβ1
    GENETICS

 and thus in

    increased or deregulated bioactivity
    BIOCHEMICAL

.

    Losartan, an angiotensin II type 1 receptor antagonist
    MEDICATION

, has been found to

    downregulate the expression of TGFβ type 1 and 2 receptors
    BIOCHEMICAL

. Clinical trials with

    losartan
    MEDICATION

 have shown a benefit in

    Marfan syndrome
    DIAGNOSIS

, while trials are underway for

    Duchenne muscular dystrophy
    DIAGNOSIS

 and other

    myopathies
    DIAGNOSIS

 associated with

    TGFβ1 signaling
    SYMPTOMS

. We hypothesized that due to its

    anti-TGFβ1 activity
    BIOCHEMICAL

,

    losartan
    MEDICATION

 might be beneficial in

    Camurati-Engelmann disease
    DIAGNOSIS

. This report concerns a

    boy
    GENDER

 who presented at

    age 13 years
    AGE

 with

    severe limb pain
    SYMPTOMS

 and

    difficulty in walking
    SYMPTOMS

.

    Clinical and radiographic evaluation
    PARACLINICAL

 results were compatible with

    Camurati-Engelmann disease
    DIAGNOSIS

 and the diagnosis was confirmed by

    mutation analysis
    PARACLINICAL

 (

    c.652C > T [p.Arg218Cys])
    GENETICS

. The

    boy
    GENDER

 underwent an

    experimental treatment with losartan at a dosage of 50 mg/day, orally
    MEDICATION

. During the

    treatment period of 18 months
    MEDICATION

, the

    intensity and frequency of limb pain decreased significantly
    SYMPTOMS

 (as shown by a pain diary), and

    muscle strength improved
    SYMPTOMS

, allowing the

    boy
    GENDER

 to

    resume walking and climbing stairs
    MEDICATION

.

    No obvious side effects
    NEG_FINDINGS

 were observed. We cautiously conclude that

    TGFβ1 inhibition with losartan
    MEDICATION

 deserves further evaluation in the clinical management of

    Camurati-Engelmann disease
    DIAGNOSIS

.

Camurati-Engelmann disease
Marfan syndrome
Duchenne muscular dystrophy
myopathies
Camurati-Engelmann disease
Camurati-Engelmann disease
Camurati-Engelmann disease


Milder course in Duchenne patients with nonsense mutations and no muscle dystrophin.

Duchenne muscular dystrophy (DMD), a severe and lethal condition, is caused by the absence of muscle dystrophin. Therapeutic trials aiming at the amelioration of muscle function have been targeting the production of muscle dystrophin in affected Duchenne patients. However, how much dystrophin is required to rescue the DMD phenotype remains an open question. We have previously identified two exceptional golden retriever muscular dystrophy (GRMD) dogs with a milder course despite the total absence of muscle dystrophin. Here we report two unusual patients carrying nonsense mutations in the DMD gene and dystrophin deficiency but with an unexpectedly mild phenotype. Three reported polymorphisms, respectively in genes LTBP4, SPP1 and ACTN3 were excluded as possible DMD genetic modifiers in our patients. Finding the mechanisms that protect some rare patients and dogs from the deleterious effect of absent muscle dystrophin is of utmost importance and may lead to new avenues for treatment. Importantly, these observations indicate that it is possible to have a functional large muscle even without dystrophin.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, a severe and lethal condition, is caused by the

    absence of muscle dystrophin
    BIOCHEMICAL

. Therapeutic trials aiming at the

    amelioration of muscle function
    SYMPTOMS

 have been targeting the

    production of muscle dystrophin
    BIOCHEMICAL

 in affected

    Duchenne
    DIAGNOSIS

 patients. However, how much dystrophin is required to rescue the

    DMD
    DIAGNOSIS

 phenotype remains an open question. We have previously identified two exceptional

    golden retriever muscular dystrophy (GRMD)
    DIAGNOSIS

 dogs with a

    milder course
    SYMPTOMS

 despite the

    total absence of muscle dystrophin
    NEG_FINDINGS

. Here we report two unusual patients carrying

    nonsense mutations in the DMD gene
    GENETICS

 and

    dystrophin deficiency
    BIOCHEMICAL

 but with an

    unexpectedly mild phenotype
    SYMPTOMS

.

    Three reported polymorphisms, respectively in genes LTBP4, SPP1 and ACTN3
    GENETICS

 were

    excluded as possible DMD genetic modifiers
    NEG_FINDINGS

 in our patients. Finding the mechanisms that protect some rare patients and dogs from the

    deleterious effect
    SYMPTOMS

 of

    absent muscle dystrophin
    NEG_FINDINGS

 is of utmost importance and may lead to new avenues for treatment. Importantly, these observations indicate that it is possible to have a

    functional large muscle
    SYMPTOMS

 even

    without dystrophin
    NEG_FINDINGS

.

absence of muscle dystrophin
production of muscle dystrophin
dystrophin deficiency

amelioration of muscle function
milder course
unexpectedly mild phenotype
deleterious effect
functional large muscle


Xp21/A translocation: a rarely considered genetic cause for manifesting carriers of duchenne muscular dystrophy.

Clinically manifesting carriers of Duchenne muscular dystrophy (DMD) are rare among the pediatric population. A standardized diagnostic procedure in supposed DMD carriers entails performing a Multiplex Ligation-dependent Probe Amplification analysis of the DMD gene first, then taking a muscle biopsy to confirm reduced dystrophin levels and/or finally a complete sequencing of the DMD gene. We describe a girl with high-elevated creatine kinase, myalgia, and cardiomyopathy. Muscle biopsy showed a dystrophic pattern and nearly absent expression of dystrophin. Diagnosis could not be confirmed by molecular genetic procedures. Because of a mild mental retardation, a chromosome analysis and molecular karyotyping were performed, revealing a balanced translocation t(X;4)(p21;q31).arr(1-22,X)x2 dn with breakpoint on the X-chromosome within an intron of the DMD gene. The inactivation of the nonderivative X-chromosome was found to be in a nonrandom pattern, resulting in a functionally balanced karyotype and thus leading to a manifesting DMD carrier in this case. Chromosome analysis should be recommended in cases of genetically unsolved DMD carriers as a part of the standard genetic procedures.

Clinically manifesting carriers of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 are rare among the

    pediatric
    AGE

 population. A standardized diagnostic procedure in supposed

    DMD
    DIAGNOSIS

 carriers entails performing a

    Multiplex Ligation-dependent Probe Amplification analysis of the DMD gene
    PARACLINICAL

 first, then taking a

    muscle biopsy
    PARACLINICAL

 to confirm

    reduced dystrophin levels
    BIOCHEMICAL

 and/or finally a

    complete sequencing of the DMD gene
    PARACLINICAL

. We describe a

    girl
    GENDER

 with

    high-elevated creatine kinase
    BIOCHEMICAL

,

    myalgia
    SYMPTOMS

, and

    cardiomyopathy
    SYMPTOMS

.

    Muscle biopsy
    PARACLINICAL

 showed a

    dystrophic pattern
    SYMPTOMS

 and

    nearly absent expression of dystrophin
    BIOCHEMICAL

. Diagnosis

    could not be confirmed by molecular genetic procedures
    NEG_FINDINGS

. Because of a

    mild mental retardation
    SYMPTOMS

, a

    chromosome analysis
    PARACLINICAL

 and

    molecular karyotyping
    PARACLINICAL

 were performed, revealing a

    balanced translocation t(X;4)(p21;q31).arr(1-22,X)x2 dn with breakpoint on the X-chromosome within an intron of the DMD gene
    GENETICS

.

    The inactivation of the nonderivative X-chromosome was found to be in a nonrandom pattern
    GENETICS

, resulting in a

    functionally balanced karyotype
    GENETICS

 and thus leading to a manifesting

    DMD
    DIAGNOSIS

 carrier in this case.

    Chromosome analysis
    PARACLINICAL

 should be recommended in cases of genetically unsolved

    DMD
    DIAGNOSIS

 carriers as a part of the standard genetic procedures.

Duchenne muscular dystrophy (DMD)
DMD
DMD
DMD

reduced dystrophin levels
high-elevated creatine kinase
nearly absent expression of dystrophin

myalgia
cardiomyopathy
dystrophic pattern
mild mental retardation


A novel dystrophin deletion mutation in a becker muscular dystrophy patient with early-onset dilated cardiomyopathy.

Becker muscular dystrophy (BMD) is a rare cause of dilated cardiomyopathy (DCM). We present a 23-year-old patient with BMD and early-onset DCM in whom cardiovascular magnetic resonance showed extensive myocardial late gadolinium enhancement and previously unreported findings of subepicardial fat infiltration in the lateral wall. In addition, this patient carried a rare mutation of dystrophin gene that might be a new genetic predisposition to early-onset DCM in BMD.

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 is a rare cause of

    dilated cardiomyopathy (DCM)
    DIAGNOSIS

. We present a

    23-year-old
    AGE

 patient with

    BMD
    DIAGNOSIS

 and

    early-onset DCM
    DIAGNOSIS

 in whom

    cardiovascular magnetic resonance
    PARACLINICAL

 showed

    extensive myocardial late gadolinium enhancement
    SYMPTOMS

 and previously unreported findings of

    subepicardial fat infiltration in the lateral wall
    MICROSCOPIC

. In addition, this patient carried a

    rare mutation of dystrophin gene
    GENETICS

 that might be a

    new genetic predisposition
    GENETICS

 to

    early-onset DCM
    DIAGNOSIS

 in

    BMD
    DIAGNOSIS

.

Becker muscular dystrophy (BMD)
dilated cardiomyopathy (DCM)
BMD
early-onset DCM
early-onset DCM
BMD

rare mutation of dystrophin gene
new genetic predisposition


The Targon PH(®) nail for distal femoral fracture fixation in disabled children. A report of three cases.

Recommendations for distal femoral fracture treatment in children with neuromuscular disease are various, including conservative, plating, nailing, and ESIN. All methods have disadvantages. Retrograde femoral intramedullary nailing using a statically interlocked Targon PH nail was performed in three cases. A right nail was used for a right femur (and vice versa). A short nail was used for supracondylar fractures, a long nail for distal femoral shaft fractures. Closed reduction was performed in all cases. Despite osteopenia, small bone dimensions and muscle dystrophy, no intraoperative or postoperative complications occurred. All cases achieved primary stability, allowing immediate rehabilitation. Bone healing occurred uneventfully within four months. No deterioration of functional status or range of motion was seen. There were no peri-implant fractures or hardware removal need over a two-year-period. Retrograde femoral nailing with the Targon PH nail seems to be a reasonable treatment concept for these rare and demanding cases.

IV.

Recommendations for

    distal femoral fracture treatment
    DIAGNOSIS

 in

    children
    AGE

 with

    neuromuscular disease
    DIAGNOSIS

 are various, including

    conservative
    MEDICATION

,

    plating
    MEDICATION

,

    nailing
    MEDICATION

, and

    ESIN
    MEDICATION

. All methods have disadvantages.

    Retrograde femoral intramedullary nailing using a statically interlocked Targon PH nail
    MEDICATION

 was performed in three cases. A

    right nail was used for a right femur
    MEDICATION

 (and vice versa).

    A short nail
    MEDICATION

 was used for

    supracondylar fractures
    MEDICATION

, a

    long nail
    MEDICATION

 for

    distal femoral shaft fractures
    DIAGNOSIS

.

    Closed reduction
    MEDICATION

 was performed in all cases. Despite

    osteopenia
    SYMPTOMS

,

    small bone dimensions
    SYMPTOMS

 and

    muscle dystrophy
    SYMPTOMS

,

    no intraoperative or postoperative complications
    NEG_FINDINGS

 occurred. All cases achieved

    primary stability
    SYMPTOMS

, allowing

    immediate rehabilitation
    MEDICATION

.

    Bone healing occurred
    SYMPTOMS

 uneventfully within four months.

    No deterioration of functional status or range of motion
    NEG_FINDINGS

 was seen. There were

    no peri-implant fractures or hardware removal need
    NEG_FINDINGS

 over a two-year-period.

    Retrograde femoral nailing with the Targon PH nail
    MEDICATION

 seems to be a reasonable treatment concept for these rare and demanding cases.

distal femoral fracture treatment
neuromuscular disease
distal femoral shaft fractures

osteopenia
small bone dimensions
muscle dystrophy
primary stability
Bone healing occurred


A novel splicing silencer generated by DMD exon 45 deletion junction could explain upstream exon 44 skipping that modifies dystrophinopathy.

Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disease, is mostly caused by exon deletion mutations in the DMD gene. The reading frame rule explains that out-of-frame deletions lead to muscle dystrophin deficiency in DMD. In outliers to this rule, deletion junction sequences have never previously been explored as splicing modulators. In a Japanese case, we identified a single exon 45 deletion in the patient's DMD gene, indicating out-of-frame mutation. However, immunohistochemical examination disclosed weak dystrophin signals in his muscle. Reverse transcription-PCR amplification of DMD exons 42 to 47 revealed a major normally spliced product with exon 45 deletion and an additional in-frame product with deletion of both exons 44 and 45, indicating upstream exon 44 skipping. We considered the latter to underlie the observed dystrophin expression. Remarkably, the junction sequence cloned by PCR walking abolished the splicing enhancer activity of the upstream intron in a chimeric doublesex gene pre-mRNA in vitro splicing. Furthermore, antisense oligonucleotides directed against the junction site counteracted this effect. These indicated that the junction sequence was a splicing silencer that induced upstream exon 44 skipping. It was strongly suggested that creation of splicing regulator is a modifier of dystrophinopathy.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, a

    progressive muscle-wasting disease
    DIAGNOSIS

, is mostly caused by

    exon deletion mutations in the DMD gene
    GENETICS

. The reading frame rule explains that

    out-of-frame deletions
    GENETICS

 lead to

    muscle dystrophin deficiency
    BIOCHEMICAL

 in

    DMD
    DIAGNOSIS

. In outliers to this rule, deletion junction sequences have never previously been explored as splicing modulators. In a

    Japanese
    ETHNICITY

 case, we identified a

    single exon 45 deletion in the patient's DMD gene
    GENETICS

, indicating

    out-of-frame mutation
    GENETICS

. However,

    immunohistochemical examination
    PARACLINICAL

 disclosed

    weak dystrophin signals in his muscle
    SYMPTOMS

.

    Reverse transcription-PCR amplification of DMD exons 42 to 47
    PARACLINICAL

 revealed a

    major normally spliced product with exon 45 deletion and an additional in-frame product with deletion of both exons 44 and 45
    GENETICS

, indicating

    upstream exon 44 skipping
    GENETICS

. We considered the latter to underlie the observed

    dystrophin expression
    BIOCHEMICAL

. Remarkably, the junction sequence cloned by

    PCR walking
    PARACLINICAL

    abolished the splicing enhancer activity of the upstream intron in a chimeric doublesex gene pre-mRNA in vitro splicing
    GENETICS

. Furthermore,

    antisense oligonucleotides directed against the
    MEDICATION

 junction site counteracted this effect. These indicated that the junction sequence was a splicing silencer that induced

    upstream exon 44 skipping
    GENETICS

. It was strongly suggested that creation of splicing regulator is a modifier of

    dystrophinopathy
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
progressive muscle-wasting disease
DMD
dystrophinopathy

muscle dystrophin deficiency
dystrophin expression


C7-T1 anterior closing wedge bone-disc-bone osteotomy for the treatment of cervical hyperlordosis in muscular dystrophy: a new technique for correction of a rare deformity.

A new surgical technique of cervical closing wedge osteotomy to correct an extension deformity of the cervical spine in patients with muscular dystrophy presenting clinically with debilitating hyperlordosis is described, and 3 cases are reported.

To describe a new surgical technique with emphasis on the clinical results and the effect of osteotomy on sagittal balance, gaze angle, and spinopelvic parameters.

Previous reports of cervical osteotomy essentially have described opening wedge (extension osteotomy) for correction of severe flexion deformities. To the authors' knowledge, C7-T1 closing wedge osteotomy to correct hyperextension deformity due to muscular dystrophy in the cervical spine has not been described previously.

Three male patients aged 16, 16, and 21 years presented with cervical hyperlordosis due to Becker muscular dystrophy. There was upward deviation of forward gaze in all patients. Anterior closing wedge (bone-disc-bone) osteotomy of C7-T1 was performed followed with a posterior release correction and instrumented stabilization. The chin-brow angle was visualized with the aid of fluoroscopy during the operation. After closure and posterior fixation, patient was turned supine again and the osteotomy site was grafted and fixed with a plate to further strengthen the construct and to prevent any translation.

The gaze angles and both sitting and standing postures of the patients markedly improved. There was documented fusion at the osteotomy sites. The patients were free of complaints at the last follow-up.

Bone-disc-bone closing wedge osteotomy done at C7-T1 level is a technically demanding procedure but results in significant acute clinical and radiological improvement in patients with hyperextension deformity of the cervical spine.

A new

    surgical technique of cervical closing wedge osteotomy to correct an extension deformity of the cervical spine
    MEDICATION

 in patients with

    muscular dystrophy
    DIAGNOSIS

 presenting clinically with

    debilitating hyperlordosis
    SYMPTOMS

 is described, and 3 cases are reported.

To describe a new surgical technique with emphasis on the clinical results and the effect of osteotomy on sagittal balance, gaze angle, and

    spinopelvic parameters
    SYMPTOMS

.

Previous reports of

    cervical osteotomy essentially
    MEDICATION

 have described

    opening wedge (extension osteotomy)
    MEDICATION

 for correction of

    severe flexion deformities
    SYMPTOMS

. To the authors' knowledge,

    C7-T1 closing wedge osteotomy
    MEDICATION

 to

    correct hyperextension deformity
    MEDICATION

 due to

    muscular dystrophy in the cervical spine
    DIAGNOSIS

 has not been described previously.

Three

    male
    GENDER

 patients

    aged 16, 16, and 21 years
    AGE

 presented with

    cervical hyperlordosis
    SYMPTOMS

 due to

    Becker muscular dystrophy
    DIAGNOSIS

. There was

    upward deviation of forward gaze
    SYMPTOMS

 in all patients.

    Anterior closing wedge (bone-disc-bone) osteotomy of C7-T1
    MEDICATION

 was performed followed with a

    posterior release correction
    MEDICATION

 and

    instrumented stabilization
    MEDICATION

. The chin-brow angle was visualized with the aid

    of fluoroscopy
    PARACLINICAL

 during the operation. After

    closure and posterior fixation
    MEDICATION

, patient was

    turned supine
    MEDICATION

 again and

    the osteotomy site was grafted and fixed with a plate to further strengthen the construct and to prevent any translation
    MEDICATION

.

The

    gaze angles and both sitting and standing postures of the patients markedly improved
    SYMPTOMS

. There was

    documented fusion at the osteotomy sites
    SYMPTOMS

. The patients were

    free of complaints
    NEG_FINDINGS

 at the last

    follow-up
    PARACLINICAL

.

    Bone-disc-bone closing wedge osteotomy done at C7-T1 level
    MEDICATION

 is a technically demanding procedure but results in

    significant acute clinical and radiological improvement
    SYMPTOMS

 in patients with

    hyperextension deformity of the cervical spine
    SYMPTOMS

.


Fecal Transplant for Treatment of Toxic Megacolon Associated With Clostridium Difficile Colitis in a Patient With Duchenne Muscular Dystrophy.

Clostridium difficile (C diff) colitis infection is the most common cause of nosocomial infectious diarrhea and the prevalence is increasing worldwide. Toxic megacolon is a severe complication of C diff colitis associated with high mortality. Gastrointestinal (GI) comorbidity and impaired smooth muscle contraction are risk factors for the development of C diff-associated toxic megacolon. We present a case of fulminant C diff colitis with toxic megacolon in a patient with Duchenne muscular dystrophy (DMD) in the intensive care unit. C diff colitis was diagnosed by clinical presentation and positive C diff DNA amplification test (polymerase chain reaction). The impairment of GI tract due to DMD predisposes these patients to severe C diff infection and toxic megacolon, as observed in this case report. For the same reason, the recovery of GI function in these patients can be prolonged. While surgery was conducted for relieving the pressure from toxic megacolon, fecal microbiota transplantation through colonoscopy resulted in successful resolution of the C diff symptoms, although the recovery is prolonged due to DMD.

    Clostridium difficile (C diff) colitis infection
    DIAGNOSIS

 is the most common cause of

    nosocomial infectious diarrhea
    DIAGNOSIS

 and the prevalence is increasing worldwide.

    Toxic megacolon
    DIAGNOSIS

 is a severe complication of

    C diff colitis
    DIAGNOSIS

 associated with high mortality.

    Gastrointestinal (GI) comorbidity
    SYMPTOMS

 and

    impaired smooth muscle contraction
    SYMPTOMS

 are risk factors for the development of

    C diff-associated toxic megacolon
    DIAGNOSIS

. We present a case of

    fulminant C diff colitis with toxic megacolon
    DIAGNOSIS

 in a patient with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 in the

    intensive care unit
    MEDICATION

.

    C diff colitis
    DIAGNOSIS

 was diagnosed by clinical presentation and

    positive C diff DNA amplification test (polymerase chain reaction)
    PARACLINICAL

. The

    impairment of GI tract
    SYMPTOMS

 due to

    DMD
    DIAGNOSIS

 predisposes these patients to

    severe C diff infection
    DIAGNOSIS

 and

    toxic megacolon
    SYMPTOMS

, as observed in this case report. For the same reason, the

    recovery of GI function
    SYMPTOMS

 in these patients can be prolonged. While

    surgery
    MEDICATION

 was conducted for

    relieving the pressure from toxic megacolon
    MEDICATION

,

    fecal microbiota transplantation through colonoscopy
    MEDICATION

 resulted in

    successful resolution of the C diff symptoms
    SYMPTOMS

, although the recovery is prolonged due to

    DMD
    DIAGNOSIS

.


What can we learn from assisted bicycle training in a girl with dystrophinopathy? A case study.

In this case study, a 9-year-old ambulatory girl with dystrophinopathy due to a mosaic translocation mutation participated in dynamic training. Because the role of exercise is unclear in both boys and girls with dystrophinopathy, a recently developed assisted bicycle training regimen was evaluated for its feasibility and effectiveness in this girl. The girl trained at home, first 15 minutes with her legs and then 15 minutes with her arms, 5 times a week, for 24 weeks. This case study showed that the training was feasible and safe. In addition, we found that no physical deterioration occurred during the training period: the Motor Function Measure and the Assisted 6-Minute Cycling Test results remained stable. Slight improvements in quantitative muscle ultrasound intensity were found, indicating less fatty infiltration in the muscles. These results suggest that physical training could be beneficial in females with dystrophinopathy who express low levels of dystrophin.

In this case study, a

    9-year-old
    AGE

    ambulatory
    AGE

    girl
    GENDER

 with

    dystrophinopathy
    DIAGNOSIS

 due to a

    mosaic translocation mutation
    GENETICS

 participated in

    dynamic training
    MEDICATION

. Because the role of

    exercise
    MEDICATION

 is unclear in both

    boys
    GENDER

 and

    girls
    GENDER

 with

    dystrophinopathy
    DIAGNOSIS

, a recently developed

    assisted bicycle training regimen
    MEDICATION

 was evaluated for its feasibility and effectiveness in this

    girl
    GENDER

. The

    girl
    GENDER

    trained at home, first 15 minutes with her legs and then 15 minutes with her arms, 5 times a week, for 24 weeks
    MEDICATION

. This case study showed that the

    training
    MEDICATION

 was feasible and safe. In addition, we found that

    no physical deterioration
    NEG_FINDINGS

 occurred during the training period: the

    Motor Function Measure and the Assisted 6-Minute Cycling Test results remained stable
    SYMPTOMS

.

    Slight improvements in quantitative muscle ultrasound intensity
    SYMPTOMS

 were found, indicating

    less fatty infiltration in the muscles
    SYMPTOMS

. These results suggest that

    physical training
    MEDICATION

 could be beneficial in

    females
    GENDER

 with

    dystrophinopathy
    DIAGNOSIS

 who express

    low levels of dystrophin
    BIOCHEMICAL

.


Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 leads to

    progressive paresis
    SYMPTOMS

,

    respiratory failure
    SYMPTOMS

 and

    premature death
    SYMPTOMS

.

    Long-term positive pressure ventilation
    MEDICATION

 can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of

    severe metabolic acidosis
    BIOCHEMICAL

 occurring in 8 of 55

    DMD
    DIAGNOSIS

 patients,

    of 20-36 years of age
    AGE

, observed over a 5-year period. All patients were

    on positive pressure ventilation
    MEDICATION

 and were being treated for

    chronic constipation
    DIAGNOSIS

. Before admission, they had had a

    reduced intake of fluids and food
    NEG_FINDINGS

. Upon examination, they were

    severely ill
    SYMPTOMS

,

    dyspneic
    SYMPTOMS

 and suffering from

    abdominal discomfort
    SYMPTOMS

.

    Metabolic acidosis with a high anion gap
    BIOCHEMICAL

 was noted in 5 of the 8 patients and with a

    normal anion gap
    NEG_FINDINGS

 in the other 3. They all recovered after the

    administration of fluids and nutrition
    MEDICATION

, the

    regulation of bowel movements
    MEDICATION

 and

    treatment with antibiotics
    MEDICATION

, as appropriate.

    Metabolic acidosis
    DIAGNOSIS

 is a life-threatening, potentially preventable complication in

    older
    AGE

    DMD
    DIAGNOSIS

 patients. Early recognition,

    subsequent administration of fluids, nutrition and antibiotics
    MEDICATION

 and

    regulation of bowel movements
    MEDICATION

 seem to be essential.

Duchenne muscular dystrophy (DMD)
DMD
chronic constipation
Metabolic acidosis
DMD

progressive paresis
respiratory failure
premature death
severely ill
dyspneic
abdominal discomfort

reduced intake of fluids and food
normal anion gap


Sugammadex and reversal of neuromuscular block in adult patient with duchenne muscular dystrophy.

Duchenne's muscular dystrophy (DMD) is the most common and severe form of myopathy. Patients with DMD are more sensitive to sedative, anesthetic, and neuromuscular blocking agents which may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. In this case report, we describe a 25-year-old male patient admitted for cholecystectomy under general anesthesia. We induced our anesthesia by oxygen, propofol, fentanyl, and rocuronium bromide. Maintenance was done by fentanyl, rocuronium bromide, sevoflurane, and O2. We report in this case the safety use of sugammadex to antagonize the neuromuscular block and rapid recovery in such category of patients.

    Duchenne's muscular dystrophy (DMD)
    DIAGNOSIS

 is the most common and severe form of

    myopathy
    DIAGNOSIS

. Patients with

    DMD
    DIAGNOSIS

 are more sensitive to

    sedative, anesthetic, and neuromuscular blocking agents
    MEDICATION

 which may result in

    intraoperative and early postoperative cardiovascular and respiratory complications
    SYMPTOMS

, as well as

    prolonged recovery from anesthesia
    SYMPTOMS

. In this case report, we describe a

    25-year-old
    AGE

    male
    GENDER

 patient admitted for

    cholecystectomy
    MEDICATION

 under

    general anesthesia
    MEDICATION

. We

    induced our anesthesia
    MEDICATION

 by

    oxygen, propofol, fentanyl, and rocuronium bromide
    MEDICATION

.

    Maintenance was done by fentanyl, rocuronium bromide, sevoflurane, and O2
    MEDICATION

. We report in this case the safety use of

    sugammadex
    MEDICATION

 to

    antagonize the neuromuscular block
    SYMPTOMS

 and

    rapid recovery
    SYMPTOMS

 in such category of patients.

Duchenne's muscular dystrophy (DMD)
myopathy
DMD


Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy - a case report.

Male, 9 FINAL DIAGNOSIS: Duchenne muscular dystrophy Symptoms: Hyporeflexia • hypotonia • weaknes of lower limbs

- Clinical Procedure: - Specialty: Neurology.

Congenital defects/diseases.

Duchenne muscular dystrophy (DMD) is a fatal, genetic, progressive, degenerating muscle disorder. Current treatment options are palliative. Newer options of cellular therapy promise to alter the disease process. Preclinical studies have successfully tested myogenic, neurogenic potential and dystrophin expression of bone marrow mononuclear cells.

We treated a 9-year-old boy suffering from DMD with serial autologous bone marrow mononuclear cell transplantations followed by multidisciplinary rehabilitation. Brooke-Vignos score was 10 and he was wheelchair-bound. Over 36 months, gradual progressive improvement was noticed in muscle strength, ambulation with assistive devices, fine motor movements, Brooke-Vignos score, and functional independence measure score. Nine months after the transplantation, electromyography findings showed development of new normal motor unit potentials of the vastus medialis muscle.

Magnetic resonance imaging scan of musculoskeletal systems showed no increase in fatty infiltration. This case report provides early investigative findings or the restorative effects of cellular therapy in DMD.

    Male
    GENDER

, 9 FINAL DIAGNOSIS:

    Duchenne muscular dystrophy
    DIAGNOSIS

    Symptoms
    SYMPTOMS

:

    Hyporeflexia
    SYMPTOMS

 •

    hypotonia
    SYMPTOMS

 • weaknes of lower limbs

- Clinical Procedure: - Specialty:

    Neurology
    MEDICATION

.

    Congenital defects/diseases
    DIAGNOSIS

.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    fatal, genetic, progressive, degenerating muscle disorder
    DIAGNOSIS

. Current treatment options are

    palliative
    NEG_FINDINGS

. Newer options of

    cellular therapy
    MEDICATION

 promise to alter the disease process. Preclinical studies have successfully tested

    myogenic, neurogenic
    SYMPTOMS

 potential and

    dystrophin expression
    BIOCHEMICAL

    of bone marrow mononuclear cells
    MICROSCOPIC

.

We treated a

    9-year-old
    AGE

    boy
    GENDER

 suffering from

    DMD
    DIAGNOSIS

 with

    serial autologous bone marrow mononuclear cell transplantations
    MEDICATION

 followed by

    multidisciplinary rehabilitation
    MEDICATION

.

    Brooke-Vignos score was 10
    SYMPTOMS

 and

    he
    GENDER

 was

    wheelchair-bound
    MEDICATION

. Over 36 months,

    gradual progressive improvement
    SYMPTOMS

 was noticed in

    muscle strength
    SYMPTOMS

,

    ambulation with assistive devices
    MEDICATION

,

    fine motor movements
    SYMPTOMS

,

    Brooke-Vignos score
    SYMPTOMS

, and

    functional independence measure score
    SYMPTOMS

. Nine months after the

    transplantation
    MEDICATION

,

    electromyography findings
    PARACLINICAL

 showed

    development of new normal motor unit potentials of the vastus medialis muscle
    SYMPTOMS

.

    Magnetic resonance imaging scan of musculoskeletal systems
    PARACLINICAL

 showed

    no increase in fatty infiltration
    NEG_FINDINGS

. This case report provides early investigative findings or the restorative effects of

    cellular therapy
    MEDICATION

 in

    DMD
    DIAGNOSIS

.

palliative
no increase in fatty infiltration


Postanesthetic death in a cat with myopathy.

There are few reports of naturally occurring muscular dystrophy in domestic animals. Herein, we describe a case of muscular dystrophy in a 4-year-old neutered male American domestic shorthair cat that died unexpectedly following anesthesia for an elective surgical procedure. Macroscopic muscular hypertrophy and histologic evidence of myofiber size variation, mineralization, myofiber degeneration, and necrosis were compatible with a diagnosis of muscular dystrophy. Extensive endomysial fibrosis was noted histologically in the diaphragm. A complete absence of dystrophin protein in Western blot confirmed the diagnosis of Duchenne muscular dystrophy. Immunofluorescence microscopy revealed reduced levels of dystrophin-associated proteins and an upregulation of utrophin at the sarcolemma. Anesthetic deaths can occur in dystrophin-deficient cats, and therefore muscular dystrophy and the associated cardiomyopathy should be considered in the differential diagnoses for perianesthetic death in cats.

There are few reports of naturally occurring

    muscular dystrophy
    DIAGNOSIS

 in

    domestic animals
    AGE

. Herein, we describe a case of

    muscular dystrophy
    DIAGNOSIS

 in a

    4-year-old
    AGE

 neutered

    male
    GENDER

    American domestic shorthair
    ETHNICITY

    cat
    GENDER

 that

    died
    SYMPTOMS

 unexpectedly following

    anesthesia
    MEDICATION

 for an

    elective surgical procedure
    MEDICATION

.

    Macroscopic muscular hypertrophy
    SYMPTOMS

 and

    histologic evidence of myofiber size variation
    SYMPTOMS

,

    mineralization
    SYMPTOMS

,

    myofiber degeneration
    MICROSCOPIC

, and

    necrosis
    MICROSCOPIC

 were compatible with a diagnosis of

    muscular dystrophy
    DIAGNOSIS

.

    Extensive endomysial fibrosis was noted histologically in the diaphragm
    MICROSCOPIC

. A

    complete absence of dystrophin protein in Western blot
    BIOCHEMICAL

 confirmed the diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Immunofluorescence microscopy
    PARACLINICAL

 revealed

    reduced levels of dystrophin-associated proteins
    BIOCHEMICAL

 and an

    upregulation of utrophin at the sarcolemma
    MICROSCOPIC

.

    Anesthetic deaths
    SYMPTOMS

 can occur in

    dystrophin-deficient
    DIAGNOSIS

    cats
    GENDER

, and therefore

    muscular dystrophy
    DIAGNOSIS

 and the associated

    cardiomyopathy
    DIAGNOSIS

 should be considered in the

    differential diagnoses
    PARACLINICAL

 for

    perianesthetic death
    SYMPTOMS

 in

    cats
    GENDER

.

muscular dystrophy
muscular dystrophy
muscular dystrophy
Duchenne muscular dystrophy
dystrophin-deficient
muscular dystrophy
cardiomyopathy


Implantation of the HeartMate II and HeartWare left ventricular assist devices in patients with duchenne muscular dystrophy: lessons learned from the first applications.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting 1 in 3,500 males, characterized by progressive skeletal muscle weakness and death secondary to cardiac or respiratory failure in the 2nd or 3rd decade. Being a progressive disease, patients are rarely candidates for cardiac transplantation and death from dilated cardiomyopathy (DCM) is common. Implantation of left ventricular assist device (LVAD) offers the potential to alter clinical trajectory by alleviating heart failure symptoms. We report implantation of HeartMate II device in a 29-year-old male patient and HeartWare device in a 23-year-old female patient, each with DMD and end-stage DCM. By improving cardiac output, we were able to achieve resolution of the symptoms of heart failure and improve their quality of life. Preoperative planning and patient selection played a significant role in the postoperative course for these patients. These cases represent the first use for each device in this patient population and the first reported LVAD implantations in patients with DMD in North America.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked recessive disorder
    GENETICS

 affecting 1 in 3,500

    males
    GENDER

, characterized by

    progressive skeletal muscle weakness
    SYMPTOMS

 and

    death
    SYMPTOMS

 secondary to

    cardiac or respiratory failure
    SYMPTOMS

 in the 2nd or 3rd decade. Being a progressive disease, patients are rarely candidates for

    cardiac transplantation
    MEDICATION

 and

    death
    SYMPTOMS

 from

    dilated cardiomyopathy (DCM)
    DIAGNOSIS

 is common.

    Implantation of left ventricular assist device (LVAD)
    MEDICATION

 offers the potential to alter clinical trajectory by

    alleviating heart failure symptoms
    SYMPTOMS

. We report

    implantation of HeartMate II device
    MEDICATION

 in a

    29-year-old
    AGE

    male
    GENDER

 patient and

    HeartWare device
    MEDICATION

 in a

    23-year-old
    AGE

    female
    GENDER

 patient, each with

    DMD
    DIAGNOSIS

 and

    end-stage DCM
    DIAGNOSIS

. By

    improving cardiac output
    SYMPTOMS

, we were able to achieve

    resolution of the symptoms of heart failure
    SYMPTOMS

 and

    improve their quality of life
    SYMPTOMS

. Preoperative planning and patient selection played a significant role in the postoperative course for these patients. These cases represent the first use for each device in this patient population and the first reported

    LVAD implantations
    MEDICATION

 in patients with

    DMD
    DIAGNOSIS

 in

    North America
    ETHNICITY

.

Duchenne muscular dystrophy (DMD)
dilated cardiomyopathy (DCM)
DMD
end-stage DCM
DMD


Balloon Kyphoplasty for Refractory Vertebral Compression Fractures in a Growing Child With Duchenne Muscular Dystrophy With Five-Year Follow-Up: Case Report and Review of Literature.

Presentation of previously unreported results and 5-year follow-up of balloon kyphoplasty used to treat an 8-year-old patient with refractory vertebral compression fractures resulting from 3 years of corticosteroid treatment for Duchenne muscular dystrophy.

Long-term corticosteroid treatment in patients with DMD has been used to try and improve muscle strength, prolong ambulation, and lower the prevalence of scoliosis. However, these patients have an increased risk of osteoporosis and vertebral fractures.

The patient was an 8-year-old boy with Duchenne muscular dystrophy who had received corticosteroid treatment for 3 years, with refractory vertebral compression fractures at T11, L1, and L3. Balloon kyphoplasty was performed at the 3 vertebral bodies using careful technique.

The patient achieved immediate pain relief after the procedure. The height of the treated vertebrae remained stable without further collapse over a 5-year follow-up period. At 5-year follow-up, the patient developed 2 new vertebral compression fractures at T12 and L2 adjacent to the treated vertebrae. The treatment also did not affect the growth of the treated vertebrae or the patient's overall growth.

Because the procedure resulted in rapid stabilization of the treated vertebrae, effective analgesia, and no effect on the growth of the treated vertebrae over a 5-year follow-up period, balloon kyphoplasty was a good therapeutic option for this pediatric patient.

Presentation of previously unreported results and 5-year follow-up of

    balloon kyphoplasty
    MEDICATION

 used to treat an

    8-year-old
    AGE

 patient with

    refractory vertebral compression fractures
    SYMPTOMS

 resulting from

    3 years of corticosteroid treatment
    MEDICATION

 for

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Long-term corticosteroid treatment
    MEDICATION

 in patients with

    DMD
    DIAGNOSIS

 has been used to try and

    improve muscle strength
    SYMPTOMS

,

    prolong ambulation
    SYMPTOMS

, and

    lower the prevalence of scoliosis
    SYMPTOMS

. However, these patients have an increased risk of

    osteoporosis
    SYMPTOMS

 and

    vertebral fractures
    SYMPTOMS

.

The patient was an

    8-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who had

    received corticosteroid treatment for 3 years
    MEDICATION

, with

    refractory vertebral compression fractures at T11, L1, and L3
    SYMPTOMS

.

    Balloon kyphoplasty was performed at the 3 vertebral bodies
    MEDICATION

 using careful technique.

The patient achieved

    immediate pain relief
    SYMPTOMS

 after

    the procedure
    MEDICATION

.

    The height of the treated vertebrae remained stable
    SYMPTOMS

    without further collapse
    NEG_FINDINGS

    over a 5-year follow-up period
    PARACLINICAL

. At

    5-year follow-up
    PARACLINICAL

, the patient developed

    2 new vertebral compression fractures at T12 and L2 adjacent to the treated vertebrae
    SYMPTOMS

. The treatment also

    did not affect the growth of the treated vertebrae or the patient's overall growth
    NEG_FINDINGS

.

Because the procedure resulted in

    rapid stabilization of the treated vertebrae
    SYMPTOMS

,

    effective analgesia
    MEDICATION

, and

    no effect on the growth of the treated vertebrae
    NEG_FINDINGS

 over a 5-year

    follow-up period
    PARACLINICAL

,

    balloon kyphoplasty
    MEDICATION

 was a good therapeutic option for this

    pediatric
    AGE

 patient.

Duchenne muscular dystrophy
DMD
Duchenne muscular dystrophy


Novel mutation in the fukutin gene in an Egyptian family with Fukuyama congenital muscular dystrophy and microcephaly.

Fukuyama-type congenital muscular dystrophy (FCMD, MIM#253800) is an autosomal recessive disorder characterized by severe muscular dystrophy associated with brain malformations. FCMD is the second most common form of muscular dystrophy after Duchenne muscular dystrophy and one of the most common autosomal recessive diseases among the Japanese population, and yet few patients outside of Japan had been reported with this disorder. We report the first known Egyptian patient with FCMD, established by clinical features of generalized weakness, pseudohypertrophy of calf muscles, progressive joint contractures, severe scoliosis, elevated serum creatine kinase level, myopathic electrodiagnostic changes, brain MRI with cobblestone complex, and mutation in the fukutin gene. In addition, our patient displayed primary microcephaly, not previously reported associated with fukutin mutations. Our results expand the geographic and clinical spectrum of fukutin mutations.

    Fukuyama-type congenital muscular dystrophy (FCMD
    DIAGNOSIS

, MIM#253800) is an

    autosomal recessive disorder
    GENETICS

 characterized by

    severe muscular dystrophy
    SYMPTOMS

 associated with

    brain malformations
    SYMPTOMS

.

    FCMD
    DIAGNOSIS

 is the second most common form of

    muscular dystrophy
    DIAGNOSIS

 after

    Duchenne muscular dystrophy
    DIAGNOSIS

 and one of the most common

    autosomal recessive diseases
    GENETICS

 among the

    Japanese
    ETHNICITY

 population, and yet few patients outside of

    Japan
    ETHNICITY

 had been reported with this disorder. We report the first known

    Egyptian
    ETHNICITY

 patient with

    FCMD
    DIAGNOSIS

, established by clinical features of

    generalized weakness
    SYMPTOMS

,

    pseudohypertrophy of calf muscles
    SYMPTOMS

,

    progressive joint contractures
    SYMPTOMS

,

    severe scoliosis
    SYMPTOMS

,

    elevated serum creatine kinase level
    BIOCHEMICAL

,

    myopathic electrodiagnostic changes
    SYMPTOMS

,

    brain MRI with cobblestone complex
    SYMPTOMS

, and

    mutation in the fukutin gene
    GENETICS

. In addition, our patient displayed

    primary microcephaly
    SYMPTOMS

, not previously reported associated with

    fukutin mutations
    GENETICS

. Our results expand the geographic and clinical spectrum of

    fukutin mutations
    GENETICS

.

autosomal recessive disorder
autosomal recessive diseases
mutation in the fukutin gene
fukutin mutations
fukutin mutations

severe muscular dystrophy
brain malformations
generalized weakness
pseudohypertrophy of calf muscles
progressive joint contractures
severe scoliosis
myopathic electrodiagnostic changes
brain MRI with cobblestone complex
primary microcephaly


Muscular dystrophy in a dog resembling human becker muscular dystrophy.

A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man.

A

    3-year-old
    AGE

,

    male
    GENDER

    Labrador retriever
    ETHNICITY

    dog
    GENDER

 was presented with

    clinical signs
    SYMPTOMS

 of

    progressive exercise intolerance
    SYMPTOMS

,

    bilateral elbow extension
    SYMPTOMS

,

    rigidity of the forelimbs
    SYMPTOMS

,

    hindlimb flexion
    SYMPTOMS

 and

    kyphosis
    SYMPTOMS

.

    Microscopical examination of muscle tissue
    PARACLINICAL

 showed

    marked variability in myofibre size
    MICROSCOPIC

,

    replacement of muscle with mature adipose tissue
    MICROSCOPIC

 and

    degeneration/regeneration of muscle fibres
    MICROSCOPIC

, consistent with

    muscular dystrophy
    DIAGNOSIS

.

    Immunohistochemical examination for dystrophin
    PARACLINICAL

 showed

    markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin
    BIOCHEMICAL

, while

    expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal
    NEG_FINDINGS

.

    Immunoblotting
    PARACLINICAL

 revealed a

    truncated dystrophin protein of approximately 135 kDa
    BIOCHEMICAL

. These findings supported a diagnosis of

    congenital canine muscular dystrophy
    DIAGNOSIS

 resembling

    Becker muscular dystrophy
    DIAGNOSIS

 in

    man
    GENDER

.

clinical signs
progressive exercise intolerance
bilateral elbow extension
rigidity of the forelimbs
hindlimb flexion
kyphosis

muscular dystrophy
congenital canine muscular dystrophy
Becker muscular dystrophy


Muscle disease.

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

On the basis of strong research evidence,

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, the most common

    severe childhood form of muscular dystrophy
    DIAGNOSIS

, is an

    X-linked recessive disorder
    GENETICS

 caused by

    out-of-frame mutations of the dystrophin gene
    GENETICS

. Thus, it is classified asa

    dystrophinopathy
    DIAGNOSIS

. The disease onset is

    before age 5 years
    AGE

. Patients with

    DMD
    DIAGNOSIS

 present with

    progressive symmetrical limb-girdle muscle weakness
    SYMPTOMS

 and become

    wheelchair dependent
    MEDICATION

 after

    age 12 years
    AGE

. (2)(3). On the basis of some research evidence,

    cardiomyopathy
    SYMPTOMS

 and

    congestive heart failure
    SYMPTOMS

 are usually seen in the

    late teens
    AGE

 in patients with

    DMD
    DIAGNOSIS

.

    Progressive scoliosis
    SYMPTOMS

 and

    respiratory in sufficiency
    SYMPTOMS

 often develop once

    wheelchair dependency
    MEDICATION

 occurs.

    Respiratory failure
    SYMPTOMS

 and

    cardiomyopathy
    SYMPTOMS

 are common causes of

    death
    SYMPTOMS

, and few survive

    beyond the third decade of life
    AGE

. (2)(3)(4)(5)(6)(7). On the basis of some research evidence,

    prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone
    MEDICATION

 (not available in the United States)

    , as a single morning dose
    MEDICATION

 is recommended for

    DMD
    DIAGNOSIS

 patients

    older than 5 years
    AGE

, which may prolong

    independent walking from a few months to 2 years
    SYMPTOMS

. (2)(3)(16)(17). Based on some research evidence,

    treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics
    MEDICATION

 has been reported to be beneficial in

    DMD
    DIAGNOSIS

 patients with

    cardiac abnormalities
    SYMPTOMS

. (2)(3)(5)(18). Based on expert opinion,

    children
    AGE

 with

    muscle weakness
    SYMPTOMS

 and

    increased serum creatine kinase levels
    BIOCHEMICAL

 may be associated with either

    genetic
    GENETICS

 or

    acquired muscle disorders
    DIAGNOSIS

 (Tables 1 and 3). (14)(15)


Co-occurring Duchenne muscular dystrophy and hypertrophic cardiomyopathy in an adult with atypical cardiac phenotype.

We present the case of a 29-year-old man with mutation-positive Duchenne muscular dystrophy and mutation-positive hypertrophic cardiomyopathy. His cardiac phenotype has characteristics of both disorders; he manifests sub-epicardial left ventricular free wall late gadolinium enhancement that is consistent with Duchenne cardiomyopathy, as well as asymmetric ventricular septal hypertrophy, hyperdynamic left ventricular systolic function, and septal mid-myocardial late gadolinium enhancement, which are characteristic of hypertrophic cardiomyopathy.

We present the case of a

    29-year-old
    AGE

    man
    GENDER

 with

    mutation-positive
    GENETICS

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    mutation-positive
    GENETICS

    hypertrophic cardiomyopathy
    DIAGNOSIS

. His

    cardiac phenotype has characteristics of both disorders
    SYMPTOMS

;

    he
    GENDER

 manifests

    sub-epicardial left ventricular free wall late gadolinium enhancement that is consistent with Duchenne cardiomyopathy
    SYMPTOMS

, as well as

    asymmetric ventricular septal hypertrophy
    SYMPTOMS

,

    hyperdynamic left ventricular systolic function
    SYMPTOMS

, and

    septal mid-myocardial late gadolinium enhancement
    SYMPTOMS

, which are characteristic of

    hypertrophic cardiomyopathy
    SYMPTOMS

.

Duchenne muscular dystrophy
hypertrophic cardiomyopathy


Prolonged Ambulation in Duchenne Patients with a Mutation Amenable to Exon 44 Skipping.

Duchenne muscular dystrophy has a severe disease course, though variability exists. Case reports suggest a milder disease course of patients amenable to exon 44 skipping. In this study, we analyzed this and show that age at wheelchair dependence in patients with a dystrophin deletion requiring exon 44 skipping is postponed compared to patients with a deletion skippable by exon 45, 51 and 53 (10.8 versus 9.8 years; P 0.020). This may be explained by more frequent spontaneous exon 44 skipping in patients with a deletion flanking exon 44. This finding has important implications for the development of future Duchenne trials.

    Duchenne muscular dystrophy
    DIAGNOSIS

 has a severe disease course, though variability exists. Case reports suggest a milder disease course of patients amenable to

    exon 44 skipping
    MEDICATION

. In this study, we analyzed this and show that

    age at wheelchair dependence
    AGE

 in patients with a

    dystrophin deletion requiring exon 44 skipping
    GENETICS

 is

    postponed
    AGE

 compared to patients with a

    deletion skippable by exon 45, 51 and 53
    GENETICS

 (

    10.8 versus 9.8 years
    AGE

; P 0.020). This may be explained by more frequent

    spontaneous exon 44 skipping
    GENETICS

 in patients with a

    deletion flanking exon 44
    GENETICS

. This finding has important implications for the development of future

    Duchenne
    DIAGNOSIS

 trials.


Challenges in the management of the child with Duchenne muscular dystrophy in a resource poor setting:a case report.

Duchenne muscular dystrophy is a progressive genetic disease with no cure at present. Children suffering from this disease eventually become wheelchair bound and die in their late teens. Paediatricians caring for the child with Duchenne Muscular Dystrophy in resource poor settings face a lot challenges. These challenges include: poverty, inadequate multidisciplinary care, emotional burn-out of parents and lack of facilities for dystrophin assay or genetic testing.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is a

    progressive genetic disease
    DIAGNOSIS

 with

    no cure
    NEG_FINDINGS

 at present.

    Children
    AGE

 suffering from this disease eventually become

    wheelchair bound
    MEDICATION

 and

    die
    SYMPTOMS

    in their late teens
    AGE

.

    Paediatricians
    PARACLINICAL

 caring for the

    child
    AGE

 with

    Duchenne Muscular Dystrophy
    DIAGNOSIS

 in resource poor settings face a lot challenges. These challenges include:

    poverty
    SYMPTOMS

,

    inadequate multidisciplinary care
    MEDICATION

,

    emotional burn-out of parents
    SYMPTOMS

 and lack of facilities for

    dystrophin assay
    PARACLINICAL

 or genetic testing.

Duchenne muscular dystrophy
progressive genetic disease
Duchenne Muscular Dystrophy

wheelchair bound
inadequate multidisciplinary care

die
poverty
emotional burn-out of parents


A new de novo mutation in a non-hot spot region at the DMD gene in a Mexican family.

In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.

In this report we present the analysis of a sporadic case of

    DMD
    DIAGNOSIS

 and his family. In the present case, a

    deletion of exons 18-47
    GENETICS

 is presented which

    predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene
    GENETICS

. This mutation was not previously reported in the Leiden database (LOVD). Both

    MLPA and segregation analysis with short tandem repeat markers
    PARACLINICAL

    elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation
    FAMILY

. This case provides a description of a

    new pathogenic variant presented as de novo mutation
    GENETICS

 in a

    DMD
    DIAGNOSIS

 patient.

    Haplotype analysis
    PARACLINICAL

 and

    complete gene screening
    PARACLINICAL

 may improve genetic counseling in cases of

    germline mosaicism
    GENETICS

 and

    de novo mutations
    GENETICS

.


Alternatives to mouthpiece noninvasive ventilatory support to permit dental care.

Patients who are dependent on continuous noninvasive intermittent positive pressure ventilation for ventilatory support via angled mouthpiece interfaces during daytime hours often need dental interventions that are prevented by the presence of the mouthpiece. To permit dental interventions, however, the noninvasive intermittent positive pressure ventilation can most conveniently and safely be delivered via nasal interface using oximetry monitoring as long as both sedation and supplemental oxygen are avoided. Three mouthpiece continuous noninvasive intermittent positive pressure ventilation users are described who were switched to nasal noninvasive intermittent positive pressure ventilation to permit dental care. The most common mistake is to fail to cover the nasal interface exhalation portals when switching from ventilatory assistance by bilevel positive airway pressure devices with passive ventilator circuits to portable ventilators with active ventilator circuits and exhalation valves.

Patients who are dependent on

    continuous noninvasive intermittent positive pressure ventilation for ventilatory support via angled mouthpiece interfaces
    MEDICATION

 during

    daytime hours
    MEDICATION

 often need

    dental interventions
    MEDICATION

 that are

    prevented by the presence of the mouthpiece
    NEG_FINDINGS

. To permit

    dental interventions
    MEDICATION

, however, the

    noninvasive intermittent positive pressure ventilation
    MEDICATION

 can most conveniently and safely be delivered via

    nasal interface
    MEDICATION

 using

    oximetry monitoring
    PARACLINICAL

 as long as

    both sedation and supplemental oxygen
    NEG_FINDINGS

 are avoided. Three

    mouthpiece continuous noninvasive intermittent positive pressure ventilation
    MEDICATION

 users are described who were

    switched to nasal noninvasive intermittent positive pressure ventilation
    MEDICATION

 to permit

    dental care
    MEDICATION

. The most common mistake is to

    fail to cover the nasal interface exhalation portals
    NEG_FINDINGS

 when

    switching from ventilatory assistance by bilevel positive airway pressure devices with passive ventilator circuits
    MEDICATION

 to

    portable ventilators with active ventilator circuits and exhalation valves
    MEDICATION

.


De novo mutation in DMD gene in a patient with combined hemophilia A and Duchenne muscular dystrophy.

We report an unusual case of a patient with two combined X-linked diseases, severe hemophilia A (HA) and Duchenne muscular dystrophy (DMD), of which only HA was hereditary. There was no family history of muscular dystrophy. Genetic analysis revealed that HA was caused by the hereditary coagulation factor VIII (F8) intron 22 inversion (distal/type I inversion), whereas DMD was caused by a de novo deletion in the dystrophin gene. This is the first report of a patient with two severe X-linked diseases, of which only HA was hereditary. Despite the fact that the probability of acquiring two X-linked abnormalities, one hereditary and one de novo, is extremely low, the emergence of such cases indicates that genetic testing for distinct X-linked diseases could be of importance in patients with hereditary hemophilia.

We report an unusual case of a patient with

    two combined X-linked diseases
    DIAGNOSIS

,

    severe hemophilia A (HA) and Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, of which only

    HA
    DIAGNOSIS

    was hereditary
    GENETICS

. There was

    no family history of muscular dystrophy
    NEG_FINDINGS

.

    Genetic analysis
    PARACLINICAL

 revealed that

    HA
    DIAGNOSIS

 was caused by the

    hereditary coagulation factor VIII (F8) intron 22 inversion (distal/type I inversion)
    GENETICS

, whereas

    DMD
    DIAGNOSIS

 was caused by a

    de novo deletion in the dystrophin gene
    GENETICS

. This is the first report of a patient with

    two severe X-linked diseases
    DIAGNOSIS

, of which only

    HA
    DIAGNOSIS

    was hereditary
    GENETICS

. Despite the fact that the probability of acquiring

    two X-linked abnormalities, one hereditary and one de novo
    GENETICS

, is extremely low, the emergence of such cases indicates that

    genetic testing
    PARACLINICAL

 for

    distinct X-linked diseases
    GENETICS

 could be of importance in patients with

    hereditary hemophilia
    DIAGNOSIS

.


Administration of glucocorticoids in boys with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common neuromuscular disease affecting boys. Advances in their care can delay the progression of DMD-related disability and prolong survival. The administration of glucocorticoids is among these advances. Glucocorticoid therapy, however, is associated with a myriad of potential adverse effects, and treating physicians as well as patients and their family members must understand the benefit/risk ratio of glucocorticoid therapy. Although current best evidence supports the use of glucocorticoids in patients with DMD, many are not offered the option. Considerable variability in practice also exists regarding when and how these drugs should be administered.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is the most common

    neuromuscular disease
    DIAGNOSIS

 affecting

    boys
    GENDER

. Advances in their care can delay the progression of DMD-related disability and prolong survival. The

    administration of glucocorticoids
    MEDICATION

 is among these advances.

    Glucocorticoid therapy
    MEDICATION

, however, is associated with a myriad of

    potential adverse effects
    SYMPTOMS

, and treating physicians as well as patients and their family members must understand the benefit/risk ratio of

    glucocorticoid therapy
    MEDICATION

. Although current best evidence supports the use of

    glucocorticoids
    MEDICATION

 in patients with

    DMD
    DIAGNOSIS

, many are not offered the option. Considerable variability in practice also exists regarding when and how these drugs should be administered.

Duchenne muscular dystrophy (DMD)
neuromuscular disease
DMD

administration of glucocorticoids
Glucocorticoid therapy
glucocorticoid therapy
glucocorticoids


The new frontier of genetically targeted therapies for muscle disease.

This article presents the case of a 5-year-old boy with Duchenne muscular dystrophy who is eligible to enroll in a clinical trial of gene therapy for this disorder. His parents are grappling with the decision about whether to enroll him. Among the issues under consideration are the potential risks and benefits to him, the costs of participating (because frequent, partially reimbursed travel is involved), and the potential cost savings of receiving this treatment on a research basis rather than as a clinically approved therapy. His parents seek the advice of his pediatric neurologist. After careful consideration of the various factors above, the pediatric neurologist explains to the family that participating in the trial is ethically permissible but that, given the uncertain benefits and potential for substantial expenses without benefit to the child, participation should not be regarded as ethically obligatory.

This article presents the case of a

    5-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who is eligible to enroll in a clinical trial of

    gene therapy
    MEDICATION

 for this

    disorder
    DIAGNOSIS

.

    His
    GENDER

 parents are grappling with the decision about whether to enroll

    him
    GENDER

. Among the issues under consideration are the potential risks and benefits to

    him
    GENDER

, the costs of participating (because frequent, partially reimbursed travel is involved), and the potential cost savings of receiving this treatment on a research basis rather than as a clinically approved therapy.

    His
    GENDER

 parents seek the advice of his

    pediatric neurologist
    PARACLINICAL

. After careful consideration of the various factors above, the

    pediatric neurologist
    PARACLINICAL

 explains to the family that participating in the trial is ethically permissible but that, given the uncertain benefits and potential for substantial expenses

    without benefit to the child
    NEG_FINDINGS

, participation should not be regarded as ethically obligatory.


Orthodontic treatment of a patient with Duchenne muscular dystrophy and macroglossia: how informed consent was critical to success.

This article describes the complex orthodontic treatment of a 22-year-old patient with Duchenne muscular dystrophy and macroglossia. His orthodontic treatment hinged on providing proper informed consent and management of the malocclusion with glossectomy, extractions, fixed appliances, and elastics. Challenges to traditional treatment are outlined, and compromises to both process and outcome are discussed from an informed consent point of view because of the serious risks involved. The treatment objectives were met, and the outcome was considered a success.

This article describes the

    complex orthodontic treatment
    MEDICATION

 of a

    22-year-old
    AGE

 patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    macroglossia
    SYMPTOMS

.

    His
    GENDER

    orthodontic treatment
    MEDICATION

 hinged on providing proper informed

    consent
    MEDICATION

 and

    management of the malocclusion
    MEDICATION

 with

    glossectomy
    MEDICATION

,

    extractions, fixed appliances, and elastics
    MEDICATION

. Challenges to

    traditional treatment
    MEDICATION

 are outlined, and compromises to both process and outcome are discussed from an informed consent point of view because of the serious risks involved. The treatment objectives were met, and the outcome was considered a success.


Use of ultrasound-guided intercostal nerve block as a sole anaesthetic technique in a high-risk patient with Duchenne muscular dystrophy.

Duchenne muscular dystrophy is a progressive neuromuscular disease. Mortality is typically related to combined respiratory failure and dilated cardiomyopathy. Surgery under general anesthesia or deep sedation presents increased risks for pulmonary complications or ventilator dependency postoperatively. We describe the utility of ultrasound guided intercostal nerve blocks for surgery on the chest wall in a patient with Duchenne muscular dystrophy and severe respiratory compromise.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is a

    progressive neuromuscular disease
    DIAGNOSIS

.

    Mortality
    SYMPTOMS

 is typically related to

    combined respiratory failure
    SYMPTOMS

 and

    dilated cardiomyopathy
    SYMPTOMS

.

    Surgery under general anesthesia or deep sedation
    MEDICATION

 presents increased risks for

    pulmonary complications
    SYMPTOMS

 or

    ventilator dependency
    SYMPTOMS

 postoperatively. We describe the utility of

    ultrasound guided intercostal nerve blocks
    PARACLINICAL

 for

    surgery on the chest wall
    MEDICATION

 in a patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    severe respiratory compromise
    SYMPTOMS

.

Duchenne muscular dystrophy
progressive neuromuscular disease
Duchenne muscular dystrophy

Mortality
combined respiratory failure
dilated cardiomyopathy
pulmonary complications
ventilator dependency
severe respiratory compromise


'Double trouble': diagnostic challenges in Duchenne muscular dystrophy in patients with an additional hereditary skeletal dysplasia.

Duchenne muscular dystrophy (DMD) is caused by mutations in Dystrophin and affects 1 in 3600-6000 males. It is characterized by progressive weakness leading to loss of ambulation, respiratory insufficiency, cardiomyopathy, and scoliosis. We describe the unusual phenotype of 3 patients with skeletal dysplasias in whom an additional diagnosis of DMD was later established. Two unrelated boys presented with osteogenesis imperfecta due to point mutations in COL1A1 and were both subsequently found to have a 1 bp frameshift deletion in the Dystrophin gene at age 3 and age 15 years, respectively. The third patient had a diagnosis of pseudoachondroplasia caused by a mutation in the COMP gene and was found to have a deletion of exons 48-50 in Dystrophin at age 9. We discuss the atypical presentation caused by the concomitant presence of 2 conditions affecting the musculoskeletal system, emphasizing aspects that may confound the presentation of a well-characterized disease like DMD. Additional series of patients with DMD and a secondary inherited condition are necessary to establish the natural history in this "double trouble" population. The recognition and accurate diagnosis of patients with two independent genetic disease processes is essential for management, prognosis, genetic risk assessment, and discussion regarding potential therapeutic interventions.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is caused by

    mutations in Dystrophin
    GENETICS

 and affects 1 in 3600-6000

    males
    GENDER

. It is characterized by

    progressive weakness
    SYMPTOMS

 leading to

    loss of ambulation
    SYMPTOMS

,

    respiratory insufficiency
    SYMPTOMS

,

    cardiomyopathy
    SYMPTOMS

, and

    scoliosis
    SYMPTOMS

. We describe the unusual phenotype of 3 patients with

    skeletal dysplasias
    DIAGNOSIS

 in whom an additional diagnosis of

    DMD
    DIAGNOSIS

 was later established. Two unrelated

    boys
    GENDER

 presented with

    osteogenesis imperfecta
    DIAGNOSIS

 due to

    point mutations in COL1A1
    GENETICS

 and were both subsequently found to have a

    1 bp frameshift deletion in the Dystrophin gene
    GENETICS

 at

    age 3 and age 15 years
    AGE

, respectively. The third patient had a diagnosis of

    pseudoachondroplasia
    DIAGNOSIS

 caused by a

    mutation in the COMP gene
    GENETICS

 and was found to have a

    deletion of exons 48-50 in Dystrophin
    GENETICS

 at

    age 9
    AGE

. We discuss the atypical presentation caused by the

    concomitant presence of 2 conditions affecting the musculoskeletal system
    SYMPTOMS

, emphasizing aspects that may confound the presentation of a well-characterized disease like

    DMD
    DIAGNOSIS

. Additional series of patients with

    DMD
    DIAGNOSIS

 and a

    secondary inherited condition
    DIAGNOSIS

 are necessary to establish the natural history in this "double trouble" population. The recognition and accurate diagnosis of patients with two independent genetic disease processes is essential for management, prognosis, genetic risk assessment, and discussion regarding potential therapeutic interventions.

Duchenne muscular dystrophy (DMD)
skeletal dysplasias
DMD
osteogenesis imperfecta
pseudoachondroplasia
DMD
DMD
secondary inherited condition


Novel mutation in exon 56 of the dystrophin gene in a child with Duchenne muscular dystrophy.

Duchenne type muscular dystrophy (DMD) is an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. Genotype analysis has shown that deletion mutations account for approximately 65% of all cases, and 5-10% are duplications, while the remaining 30% of affected individuals may have smaller mutations, including point mutations, small deletions or small insertions. In this study, we present the case of a 4-year-old boy with typical clinical features of DMD, who developed normally until the age of 2. However, at age 3 he presented his first symptom, a tendency to fall, had difficulty in rising from the floor and in walking on his toes. At age 4 he had a waddling gait and could no longer climb stairs. A physical examination revealed proximal muscle weakness, calf hypertrophy, deep tendon hyporflexia and a positive Gower's sign. To identify the disease-causing gene in the proband, all coding regions (exons 1-79) of the dystrophin gene were PCR-amplified and sequenced. A novel duplication (c.8284dupA) in exon 56 of the dystrophin gene was identified, which was predicted to generate a frameshift mutation and create a premature termination codon (p.Ile2762Asnfs*10). This mutation was further confirmed by single-strand conformation polymorphism (SSCP) analysis, which revealed an extra band found in exon 56 of the dystrophin in the proband; however, this was not present in his family members or in the 100 matched normal controls. The data presented in this study may aid in expanding the spectrum of mutations causing DMD. To our knowledge, we demonstrate for the first time that a small duplication mutation can cause severe DMD.

    Duchenne type muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    allelic X-linked recessive disorder
    GENETICS

 caused by

    mutations in the gene encoding dystrophin
    GENETICS

.

    Genotype analysis
    PARACLINICAL

 has shown that

    deletion mutations
    GENETICS

 account for approximately 65% of all cases, and 5-10% are

    duplications
    GENETICS

, while the remaining 30% of affected individuals may have

    smaller mutations
    GENETICS

, including

    point mutations, small deletions or small insertions
    GENETICS

. In this study, we present the case of a

    4-year-old
    AGE

    boy
    GENDER

 with

    typical clinical features of DMD
    SYMPTOMS

, who developed normally

    until the age of 2
    AGE

. However, at

    age 3
    AGE

    he
    GENDER

 presented his first symptom, a

    tendency to fall
    SYMPTOMS

, had

    difficulty in rising from the floor and in walking on his toes
    SYMPTOMS

. At

    age 4
    AGE

    he
    GENDER

 had a

    waddling gait
    SYMPTOMS

 and

    could no longer climb stairs
    NEG_FINDINGS

. A

    physical examination
    PARACLINICAL

 revealed

    proximal muscle weakness
    SYMPTOMS

,

    calf hypertrophy
    SYMPTOMS

,

    deep tendon hyporflexia
    SYMPTOMS

 and a

    positive Gower's sign
    SYMPTOMS

. To identify the disease-causing gene in the proband,

    all coding regions (exons 1-79) of the dystrophin gene were PCR-amplified and sequenced
    PARACLINICAL

. A

    novel duplication (c.8284dupA) in exon 56 of the dystrophin gene
    GENETICS

 was identified, which

    was predicted to generate a frameshift mutation and create a premature termination codon (p.Ile2762Asnfs*10)
    GENETICS

. This mutation was further confirmed by

    single-strand conformation polymorphism (SSCP) analysis
    PARACLINICAL

, which revealed an

    extra band found in exon 56 of the dystrophin
    GENETICS

 in the proband; however, this was not present in his family members or in the 100 matched normal controls. The data presented in this study may aid in expanding the spectrum of mutations causing

    DMD
    DIAGNOSIS

. To our knowledge, we demonstrate for the first time that a

    small duplication mutation
    GENETICS

 can cause

    severe DMD
    DIAGNOSIS

.

Duchenne type muscular dystrophy (DMD)
DMD
severe DMD


Prenatal diagnosis of BMD in Morocco: evolution and limits.

The muscular dystrophy is a group of inherited disorders characterized in the most of cases by progressive muscle weakness. The best known are X-linked disorder Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). BMD is a milder form of the disease with a later age of onset and a slower clinical progression. The DMD gene, located on Xp21, is the largest human gene in the human genome (2.3 Mb). DMD gene consists of 79 exons and codes for dystrophin protein. A 9-year-old boy, who experienced symptoms of the disease, was admitted to the Casablanca University Children's Hospital. The patient, with no known family history of significant muscle disease, was first examined at 4 years of age because of walking difficulties and a limited hands force. Blood tests revealed elevated serum levels of creatine kinase (7.60 U/L). The electromyogram showed myopathic changes, consisting of polyphasic potentials, and the muscular biopsy revealed dystrophic aspect. Analysis of the dystrophin-encoding gene by PCR deletion analysis of the dystrophin gene was performed by multiplex PCR primer sets of Chamberlain and Beggs. The analysis showed a deletion of exons 45 to 49. Mother genetic testing showed the heterozygosis deletion.

The

    muscular dystrophy
    DIAGNOSIS

 is a group of

    inherited disorders
    GENETICS

 characterized in the most of cases by

    progressive muscle weakness
    SYMPTOMS

. The best known are

    X-linked disorder Duchenne muscular dystrophy (DMD)
    GENETICS

 and

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

.

    BMD
    DIAGNOSIS

 is a milder form of the disease with a

    later age of onset
    AGE

 and a slower clinical progression.

    The DMD gene, located on Xp21, is the largest human gene in the human genome (2.3 Mb)
    GENETICS

.

    DMD gene consists of 79 exons and codes for dystrophin protein
    GENETICS

. A

    9-year-old
    AGE

    boy
    GENDER

, who experienced

    symptoms of the disease
    SYMPTOMS

, was admitted to the Casablanca University Children's Hospital. The patient,

    with no known family history of significant muscle disease
    NEG_FINDINGS

, was first examined at

    4 years of age
    AGE

 because of

    walking difficulties
    SYMPTOMS

 and a

    limited hands force
    SYMPTOMS

.

    Blood tests
    PARACLINICAL

 revealed

    elevated serum levels of creatine kinase (7.60 U/L)
    BIOCHEMICAL

. The

    electromyogram
    PARACLINICAL

 showed

    myopathic changes, consisting of polyphasic potentials
    SYMPTOMS

, and the

    muscular biopsy
    PARACLINICAL

 revealed

    dystrophic aspect
    SYMPTOMS

.

    Analysis of the dystrophin-encoding gene by PCR deletion analysis of the dystrophin gene
    PARACLINICAL

 was performed by

    multiplex PCR primer sets of Chamberlain and Beggs
    PARACLINICAL

. The analysis showed a

    deletion of exons 45 to 49
    GENETICS

.

    Mother genetic testing
    PARACLINICAL

 showed the

    heterozygosis deletion
    GENETICS

.

muscular dystrophy
Becker muscular dystrophy (BMD)
BMD