Three cases of manifesting female carriers in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy usually affects males. However, females are also affected in rare instances. Approximately 8% of female Duchenne muscular dystrophy (DMD) carriers are manifesting carriers and have muscle weakness to some extent. We investigated the clinical features of 3 female patients with dystrophinopathy diagnosed by clinical, pathological, and genetic studies at our neuromuscular disease clinic. The onset age of manifesting symptoms varied (8-28 years). Muscle weakness grade varied as follows: patient 1 showed asymmetrical bilateral proximal upper and lower extremities weakness, patient 2 showed asymmetrical bilateral upper extremities weakness similar to scapulohumoral muscular dystrophy, and patient 3 had only bilateral asymmetric proximal lower extremities weakness. Two patients had familial histories of DMD (their sons were diagnosed with DMD), but the 1 remaining patient had no familial history of DMD. The serum creatine kinase level was elevated in all patients, but it was not correlated with muscular weakness. An electromyography study showed findings of myopathy in all patients. One patient was diagnosed with a DMD carrier by a muscle biopsy with an immunohistochemical stain (dystrophin). The remaining 2 patients with familial history of DMD were diagnosed by multiplex ligation-dependent probe amplification (MLPA). There were inconsistent clinical features in the female carriers. An immunohistochemical analysis of dystrophin could be useful for female carrier patients. Also, multiplex ligation-dependent probe amplification is essential for the diagnosis of a manifesting female carrier DMD in female myopathic patients because conventional multiplex PCR could not detect the duplication and is less accurate compared to MLPA.

    Duchenne muscular dystrophy
    DIAGNOSIS

 usually affects

    males
    GENDER

. However,

    females
    GENDER

 are also affected in rare instances. Approximately 8% of

    female
    GENDER

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 carriers are manifesting carriers and have

    muscle weakness
    SYMPTOMS

 to some extent. We investigated the clinical features of 3

    female
    GENDER

 patients with

    dystrophinopathy
    DIAGNOSIS

 diagnosed by

    clinical, pathological, and genetic studies
    PARACLINICAL

 at our

    neuromuscular disease
    DIAGNOSIS

 clinic. The

    onset age of manifesting symptoms
    AGE

 varied

    (8-28 years)
    AGE

.

    Muscle weakness grade
    SYMPTOMS

 varied as follows: patient 1 showed

    asymmetrical bilateral proximal upper and lower extremities weakness
    SYMPTOMS

, patient 2 showed

    asymmetrical bilateral upper extremities weakness similar to scapulohumoral muscular dystrophy
    SYMPTOMS

, and patient 3 had

    only bilateral asymmetric proximal lower extremities weakness
    SYMPTOMS

. Two patients

    had familial histories of DMD (their sons were diagnosed with DMD)
    FAMILY

, but the 1 remaining patient had

    no familial history of DMD
    FAMILY

. The

    serum creatine kinase level was elevated
    BIOCHEMICAL

 in all patients, but it was

    not correlated with muscular weakness
    NEG_FINDINGS

. An

    electromyography study
    PARACLINICAL

 showed

    findings of myopathy
    SYMPTOMS

 in all patients. One patient was diagnosed with a

    DMD
    DIAGNOSIS

 carrier by a

    muscle biopsy
    PARACLINICAL

 with an

    immunohistochemical stain (dystrophin)
    PARACLINICAL

. The remaining 2 patients with

    familial history of DMD
    FAMILY

 were diagnosed by

    multiplex ligation-dependent probe amplification (MLPA)
    PARACLINICAL

. There were

    inconsistent clinical features
    SYMPTOMS

 in the

    female
    GENDER

 carriers. An

    immunohistochemical analysis of dystrophin
    PARACLINICAL

 could be useful for

    female
    GENDER

 carrier patients. Also,

    multiplex ligation-dependent probe amplification
    PARACLINICAL

 is essential for the diagnosis of a manifesting

    female
    GENDER

 carrier

    DMD
    DIAGNOSIS

 in

    female
    GENDER

    myopathic
    DIAGNOSIS

 patients because

    conventional multiplex PCR
    PARACLINICAL

 could not detect the duplication and is less accurate compared to

    MLPA
    PARACLINICAL

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD)
dystrophinopathy
neuromuscular disease
DMD
DMD
myopathic


Targeting parents for the treatment of pediatric obesity in boys with Duchenne muscular dystrophy: a case series.

Obesity is a major public health concern in children. Obesity occurs frequently in boys with Duchenne muscular dystrophy (DMD), complicating treatment and impairing functioning. Parent-focused interventions to facilitate weight loss have been successful in other pediatric samples but have not been studied with this population. The current investigation examined the feasibility and potential efficacy of parent-focused treatment to improve healthy eating and physical activity of parents and eating and weight in their sons with DMD. Three families participated in this case series. Resulting changes in body weight among boys with DMD were an outcome variable. Findings indicate inconsistent changes in boys' weight, decreases in parent weight, increases in healthy foods available in the home, and increases in children's perceived quality of life. Participant ratings of treatment suitability and satisfaction were generally favorable. These preliminary findings support the use of parent-focused psychoeducation for the treatment of obesity in children with DMD.

    Obesity
    DIAGNOSIS

 is a major public health concern in

    children
    AGE

.

    Obesity
    SYMPTOMS

 occurs frequently in

    boys
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, complicating treatment and impairing functioning.

    Parent-focused interventions
    MEDICATION

 to facilitate

    weight loss
    MEDICATION

 have been successful in other

    pediatric
    AGE

 samples but have not been studied with this population. The current investigation examined the feasibility and potential efficacy of

    parent-focused treatment
    MEDICATION

 to improve healthy eating and physical activity of parents and eating and weight in their

    sons
    GENDER

 with

    DMD
    DIAGNOSIS

. Three families participated in this case series. Resulting changes in

    body weight
    SYMPTOMS

 among

    boys
    GENDER

 with

    DMD
    DIAGNOSIS

 were an outcome variable. Findings indicate

    inconsistent changes in boys' weight
    SYMPTOMS

,

    decreases in parent weight
    SYMPTOMS

, increases in healthy foods available in the home, and

    increases in children's perceived quality of life
    SYMPTOMS

. Participant ratings of treatment suitability and satisfaction were generally favorable. These preliminary findings support the use of

    parent-focused psychoeducation
    MEDICATION

 for the treatment of

    obesity
    DIAGNOSIS

 in

    children
    AGE

 with

    DMD
    DIAGNOSIS

.

Obesity
Duchenne muscular dystrophy (DMD)
DMD
DMD
obesity
DMD

Parent-focused interventions
weight loss
parent-focused treatment
parent-focused psychoeducation


Opportunities for people with disabilities in the virtual world of Second Life.

The virtual world of Second Life (SL) offers people with disabilities a chance to explore new worlds without being limited by their disabilities. Many people with disabilities use SL for information, support, and entertainment. SL is a computer-based simulated environment in which participants are represented by a human-like avatar. The avatar can move through the environment, manipulate objects, and participate in day-to-day activities that most people take for granted, such as walking, dancing, and communicating. In this article, the authors focus on the benefits that information, socialization, and community membership can offer people with disabilities and some of the resources that are available for them in SL. SL communities, groups, and activities also help increase self-worth and empower people with disabilities. Participating in a virtual world enriches the overall quality of life of people with disabilities and may enhance their physical, emotional, and social adjustment.

The

    virtual world of Second Life (SL)
    MEDICATION

 offers people with

    disabilities
    DIAGNOSIS

 a chance to explore new worlds

    without being limited by their disabilities
    NEG_FINDINGS

. Many people with

    disabilities
    DIAGNOSIS

 use

    SL
    MEDICATION

 for information, support, and

    entertainment
    MEDICATION

.

    SL
    MEDICATION

 is a computer-based simulated environment in which participants are represented by a

    human-like avatar
    MEDICATION

. The avatar can move through the environment,

    manipulate objects
    MEDICATION

, and

    participate in day-to-day
    MEDICATION

 activities that most people take for granted, such as

    walking
    MEDICATION

,

    dancing
    MEDICATION

, and communicating. In this article, the authors focus on the benefits that

    information, socialization, and community membership
    MEDICATION

 can offer people with

    disabilities
    DIAGNOSIS

 and some of the resources that are available for them in

    SL
    MEDICATION

.

    SL communities, groups
    MEDICATION

, and activities also help

    increase self-worth
    SYMPTOMS

 and empower people with

    disabilities
    AGE

.

    Participating in a virtual world
    MEDICATION

 enriches the overall quality of life of people with

    disabilities
    DIAGNOSIS

 and may enhance their

    physical, emotional, and social adjustment
    SYMPTOMS

.

disabilities disabilities disabilities disabilities


Duchenne muscular dystrophy caused by a complex rearrangement between intron 43 of the DMD gene and chromosome 4.

Deletions/duplications of exons in the DMD gene cause about 70% of all cases of Duchenne muscular dystrophy (DMD). Most remaining mutations are point mutations or small insertion-deletions located mainly in the coding but also in deep intronic regions of the DMD gene. We describe a novel complex rearrangement in a patient affected with DMD that was undetectable using standard molecular diagnostic methods. Analysis of the proband's mRNA from a muscle biopsy revealed the insertion of an 80 bp cryptic exon from chromosome 4 between exons 43 and 44 of the dystrophin gene. Array comparative genomic hybridization and breakpoint junction sequence analysis indicated this cryptic exon originated from a complex genomic 90 kb insertion of non-coding chromosome 4 into intron 43 of the dystrophin gene. This rearrangement was also detectable in the patient's mother. The genomic characterization of this novel complex mutation was essential for accurate carrier and genetic counseling of this family and emphasizes the need for comprehensive molecular diagnosis of patients with clinical signs of DMD and clear pathological changes.

    Deletions/duplications of exons in the DMD gene
    GENETICS

 cause about 70% of all cases of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Most remaining mutations are

    point mutations or small insertion-deletions located mainly in the coding but also in deep intronic regions of the DMD gene
    GENETICS

. We describe a

    novel complex rearrangement
    GENETICS

 in a patient affected with

    DMD
    DIAGNOSIS

 that was

    undetectable using standard molecular diagnostic methods
    NEG_FINDINGS

.

    Analysis of the proband's mRNA from a muscle biopsy
    PARACLINICAL

 revealed the

    insertion of an 80 bp cryptic exon from chromosome 4 between exons 43 and 44 of the dystrophin gene
    GENETICS

.

    Array comparative genomic hybridization and breakpoint junction sequence analysis
    PARACLINICAL

 indicated this

    cryptic exon originated from a complex genomic 90 kb insertion of non-coding chromosome 4 into intron 43 of the dystrophin gene
    GENETICS

.

    This rearrangement was also detectable in the patient's mother
    FAMILY

. The genomic characterization of this

    novel complex mutation
    GENETICS

 was essential for accurate carrier and genetic counseling of this family and emphasizes the need for comprehensive

    molecular diagnosis
    PARACLINICAL

 of patients with

    clinical signs of DMD
    SYMPTOMS

 and

    clear pathological changes
    SYMPTOMS

.

clinical signs of DMD
clear pathological changes


[Late onset Becker muscular dystrophy. A case report and literature review].

The first manifestations of Becker's muscular dystrophy usually occur during childhood, as Duchenne's muscular dystrophy, a related disease. However, clinical presentation is usually more heterogeneous and less severe.

We report a 54-year-old man who presented with a late onset of Becker's muscular dystrophy, and review 12 additional similar cases previously reported in the literature. The disease onset ranged from 30 to 65 years old. Genetic deletion involved mainly exons 45 to 55 with variable phenotype: distal muscular hypertrophy in four cases, cardiac involvement (electrocardiography, radiography or echocardiography) in six out of the 12 studied cases. Compared to the paediatric form, functional impairment was milder, as only three patients after seven to 20 years of follow-up were wheelchair bound.

The first manifestations of Becker's muscular dystrophy may occur after the age of 30 with heterogeneous phenotypes. Severity and limb disability is milder in these patients.

The first manifestations of

    Becker's muscular dystrophy
    DIAGNOSIS

 usually occur

    during childhood
    AGE

, as

    Duchenne's muscular dystrophy
    DIAGNOSIS

, a related disease. However, clinical presentation is usually more heterogeneous and less severe.

We report a

    54-year-old
    AGE

    man
    GENDER

 who presented with a

    late onset of Becker's muscular dystrophy
    DIAGNOSIS

, and review 12 additional similar cases previously reported in the literature. The disease

    onset ranged from 30 to 65 years old
    AGE

.

    Genetic deletion involved mainly exons 45 to 55
    GENETICS

 with variable phenotype:

    distal muscular hypertrophy
    SYMPTOMS

 in four cases,

    cardiac involvement
    SYMPTOMS

 (

    electrocardiography
    PARACLINICAL

,

    radiography
    PARACLINICAL

 or

    echocardiography
    PARACLINICAL

) in six out of the 12 studied cases. Compared to the paediatric form,

    functional impairment was milder
    SYMPTOMS

, as only three patients after seven to 20 years of follow-up were

    wheelchair bound
    MEDICATION

.

The first manifestations of

    Becker's muscular dystrophy
    DIAGNOSIS

 may occur

    after the age of 30
    AGE

 with heterogeneous phenotypes. Severity and

    limb disability
    SYMPTOMS

 is milder in these patients.

distal muscular hypertrophy
cardiac involvement
functional impairment was milder
limb disability


An unusual case of left ventricular aneurysm in duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) leads to structural heart disease, including dilated cardiomyopathy, in 90% of patients >18 years of age. Despite the ubiquity of cardiomyopathy associated with DMD, ventricular aneurysms in these patients have rarely been reported. We present a case of a basal inferoposterior aneurysm of the left ventricle in a 23-year-old male patient with DMD.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 leads to

    structural heart disease
    DIAGNOSIS

, including

    dilated cardiomyopathy
    DIAGNOSIS

, in 90% of patients

    >18 years of age
    AGE

. Despite the ubiquity of

    cardiomyopathy
    DIAGNOSIS

 associated with

    DMD
    DIAGNOSIS

,

    ventricular aneurysms
    SYMPTOMS

 in these patients have rarely been reported. We present a case of a

    basal inferoposterior aneurysm of the left ventricle
    SYMPTOMS

 in a

    23-year-old
    AGE

    male
    GENDER

 patient with

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
structural heart disease
dilated cardiomyopathy
cardiomyopathy
DMD
DMD


High frequency chest wall oscillation plus mechanical in-exsufflation in Duchenne muscular dystrophy with respiratory complications related to pandemic Influenza A/H1N1.

Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1), had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy.

Two

    young
    AGE

    boys
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

, who had contracted

    2009 pandemic influenza A/H1N1 (pH1N1)
    DIAGNOSIS

, had been

    treated with antibiotics and steroids
    NEG_FINDINGS

    without significant improvement
    NEG_FINDINGS

. One of them showed

    severe scoliosis
    SYMPTOMS

. After hospitalization

    chest CT scan
    PARACLINICAL

 revealed

    extensive pulmonary bilateral segmental atelectasis
    SYMPTOMS

. Their

    clinical and radiological findings rapidly improved
    SYMPTOMS

 when a

    sequential respiratory physiotherapy protocol
    MEDICATION

 was adopted that consisted of the

    application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres
    MEDICATION

. The protocol was well tolerated, effective, easy to apply and

    special positioning was not required
    NEG_FINDINGS

. Fifteen days after treatment initiation both patients

    clinically recovered
    SYMPTOMS

. This treatment can be very helpful for

    neuromuscular
    DIAGNOSIS

 patients, particularly when

    scoliosis prevents conventional respiratory physiotherapy
    NEG_FINDINGS

.

Duchenne muscular dystrophy
2009 pandemic influenza A/H1N1 (pH1N1)
neuromuscular


Duchenne muscular dystrophy in a female patient with a karyotype of 46,X,i(X)(q10).

Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy caused by mutations in the dystrophin gene and it affects males predominantly. Here we report a 4-year-old girl with DMD from a healthy family, in which her parents and sister have no DMD genotype. A PCR-based method of multiple ligation-dependent probe amplification (MLPA) analysis showed the deletion of exons 46 and 47 in the dystrophin gene, which led to loss of dystrophin function. No obvious phenotype of Turner syndrome was observed in this patient and cytogenetic analysis revealed that her karyotype is 46,X,i(X)(q10). In conclusion, we describe the first female patient with DMD who carries a de novo mutation of the dystrophin gene in one chromosome and isochromosome Xq, i(Xq), in another chromosome.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    severe recessive X-linked
    DIAGNOSIS

    form of muscular dystrophy
    DIAGNOSIS

 caused by

    mutations in the dystrophin gene
    GENETICS

 and it affects

    males
    GENDER

 predominantly. Here we report a

    4-year-old
    AGE

    girl
    GENDER

 with

    DMD
    DIAGNOSIS

 from a

    healthy family, in which her parents and sister have no DMD genotype
    FAMILY

. A

    PCR-based method of multiple ligation-dependent probe amplification (MLPA) analysis
    PARACLINICAL

 showed the

    deletion of exons 46 and 47 in the dystrophin gene
    GENETICS

, which led to

    loss of dystrophin function
    BIOCHEMICAL

.

    No obvious phenotype of Turner syndrome
    NEG_FINDINGS

    was observed
    NEG_FINDINGS

 in this patient and

    cytogenetic analysis
    PARACLINICAL

 revealed that

    her
    GENDER

    karyotype is 46,X,i(X)(q10)
    GENETICS

. In conclusion, we describe the first

    female
    GENDER

 patient with

    DMD
    DIAGNOSIS

 who carries a

    de novo mutation of the dystrophin gene in one chromosome and isochromosome Xq, i(Xq), in another chromosome
    GENETICS

.

Duchenne muscular dystrophy (DMD)
severe recessive X-linked
form of muscular dystrophy
DMD
DMD


Complete immobility as a potential biomechanical complication of Achilles tendon lengthening.

Proximal muscle weakness is a common association of muscular dystrophies. Knees and hip extensor weakness limit the patients' ability to counteract flexor knee joints' moments. Therefore, patients try to toe walk to move the ground reaction force (GRF) anteriorly to help to stabilise the knee. We report a case of a patient with Becker's muscular dystrophy who lost his ability to walk completely following a bilateral Achilles tendons operation. The patient's ability to heel-strike moved his GRF posteriorly resulting in creation of excessive knees flexion moments. Three years following the operation and following a lengthy rehabilitation programme, the patient managed to mobilise using an orthosis.

    Proximal muscle weakness
    SYMPTOMS

 is a common association of

    muscular dystrophies
    DIAGNOSIS

.

    Knees and hip extensor weakness
    SYMPTOMS

 limit the patients'

    ability to counteract flexor knee joints' moments
    NEG_FINDINGS

. Therefore, patients try to

    toe walk to move the ground reaction force (GRF) anteriorly
    MEDICATION

 to help to

    stabilise the knee
    MEDICATION

. We report a case of a patient with

    Becker's muscular dystrophy
    DIAGNOSIS

 who

    lost his ability to walk completely
    SYMPTOMS

 following a

    bilateral Achilles tendons operation
    MEDICATION

. The patient's

    ability to heel-strike moved his GRF posteriorly
    MEDICATION

 resulting in

    creation of excessive knees flexion moments
    SYMPTOMS

. Three years following

    the operation
    MEDICATION

 and

    following a lengthy rehabilitation programme
    MEDICATION

, the patient

    managed to mobilise using an orthosis
    MEDICATION

.

muscular dystrophies
Becker's muscular dystrophy


Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA.

Non-autonomous retrotransposon-mediated mobilizations of the Alu family are known pathogenic mechanisms of human disease. Here, we report a pathogenic, contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene. In a Japanese Duchenne muscular dystrophy patient, a 330-bp-long de novo insertion was identified in exon 67 of dystrophin. The insertion induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon. The sequence of the insertion had certain characteristics of retrotransposons: an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication. The insertion site matched the consensus recognition sequence for the L1 endonuclease, indicating a retrotransposon-mediated event, although the inserted sequence did not match any known retrotransposons. The origin of the inserted sequence was mapped to a gene-poor region of chromosome 11. The inserted fragment was expressed in multiple human tissue RNAs, indicating that it is a novel transcript. The full length of the transcript was cloned and showed no meaningful protein coding ability.

    Non-autonomous retrotransposon-mediated mobilizations of the Alu family
    GENETICS

 are known pathogenic mechanisms of human disease. Here, we report a pathogenic,

    contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene
    GENETICS

. In a

    Japanese
    ETHNICITY

    Duchenne muscular dystrophy
    DIAGNOSIS

 patient, a

    330-bp-long de novo insertion was identified in exon 67 of dystrophin
    GENETICS

. The insertion

    induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon
    GENETICS

. The

    sequence of the insertion had certain characteristics of retrotransposons
    GENETICS

    : an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication
    GENETICS

. The insertion site

    matched the consensus recognition sequence for the L1 endonuclease
    GENETICS

, indicating a

    retrotransposon-mediated event
    GENETICS

, although the inserted

    sequence did not match any known retrotransposons
    NEG_FINDINGS

. The

    origin of the inserted sequence was mapped to a gene-poor region of chromosome 11
    GENETICS

. The inserted fragment was

    expressed in multiple human tissue RNAs
    MICROSCOPIC

, indicating that it is a

    novel transcript
    GENETICS

. The full length of the transcript was cloned and showed

    no meaningful protein coding ability
    NEG_FINDINGS

.


Joseph's wishes: ethical decision-making in Duchenne muscular dystrophy.

The death of a child is an uncommon occurrence and can be difficult for families to accept. Attempts by the healthcare team to discuss end-of-life issues can be so upsetting to families that they refuse to participate in the discussion. Even with diseases where an early death can be anticipated, such as Duchenne muscular dystrophy, the family is often reluctant to discuss end-of-life issues when the patient is relatively healthy, preferring to focus on the current health issues. In this article we discuss what happens when there are disagreements between the patient and family and the needs of both must be taken into consideration.

The

    death
    SYMPTOMS

 of a

    child
    AGE

 is an uncommon occurrence and can be difficult for families to accept. Attempts by the healthcare team to discuss end-of-life issues can be so upsetting to families that they

    refuse to participate
    NEG_FINDINGS

 in the discussion. Even with diseases where an

    early death
    SYMPTOMS

 can be anticipated, such as

    Duchenne muscular dystrophy
    DIAGNOSIS

, the family is often

    reluctant to discuss
    NEG_FINDINGS

 end-of-life issues when the patient is relatively healthy, preferring to focus on the current health issues. In this article we discuss what happens when there are disagreements between the patient and family and the needs of both must be taken into consideration.

refuse to participate
reluctant to discuss


Unexpected detection of dystrophin gene deletions by array comparative genomic hybridization.

Array comparative genomic hybridization has increasingly become the standard of care to evaluate patients for genomic imbalance. As the patient population evaluated by microarray expands, there is certain to be an increase in the detection of unexpected, yet common diseases. When array results predict a late-onset disorder or cancer predisposition, it becomes a challenge for physicians and counselors to adequately address with patients. Included in this study were three patients described with nonspecific phenotypic findings who underwent microarray testing to better define their disease etiology. An unexpected deletion within the dystrophin gene was observed in each case, despite that no patient was suspected of a dystrophinopathy at the time of testing. The patients included an 8-day-old male with a dystrophin deletion predictive of Becker muscular dystrophy, an 18-month old female found to be the carrier of deletion, and a 4-year-8-month-old male with a deletion predictive of Duchenne muscular dystrophy. In this circumstance it becomes difficult to counsel the family, as well as to predict disease course when underlying medical conditions may exist. However, early detection may enable the patient to receive proactive treatment, and allows for screening of at-risk family members. Ultimately, it is up to the clinician to promote informed decision-making within the family prior to testing, and ensure that adequate counseling is provided during follow-up.

    Array comparative genomic hybridization
    PARACLINICAL

 has increasingly become the standard of care to evaluate patients for

    genomic imbalance
    PARACLINICAL

. As the patient population evaluated by microarray expands, there is certain to be an increase in the detection of unexpected, yet common diseases. When array results predict a

    late-onset disorder
    DIAGNOSIS

 or

    cancer predisposition
    DIAGNOSIS

, it becomes a challenge for physicians and counselors to adequately address with patients. Included in this study were three patients described with

    nonspecific phenotypic findings
    SYMPTOMS

 who underwent

    microarray testing
    PARACLINICAL

 to better define their disease etiology. An

    unexpected deletion within the dystrophin gene
    GENETICS

 was observed in each case,

    despite that no patient was suspected of a dystrophinopathy
    NEG_FINDINGS

    at the time of testing
    NEG_FINDINGS

. The patients included an

    8-day-old
    AGE

    male
    GENDER

 with a

    dystrophin deletion predictive of Becker muscular dystrophy
    GENETICS

, an

    18-month old
    AGE

    female
    GENDER

 found to be the

    carrier of deletion
    FAMILY

, and a

    4-year-8-month-old
    AGE

    male
    GENDER

 with a

    deletion predictive
    GENETICS

 of

    Duchenne muscular dystrophy
    DIAGNOSIS

. In this circumstance it becomes difficult to counsel the family, as well as to predict disease course when underlying medical conditions may exist. However, early detection may enable the patient to receive

    proactive treatment
    MEDICATION

, and allows for screening of at-risk family members. Ultimately, it is up to the clinician to promote informed decision-making within the family prior to testing, and ensure that adequate counseling is provided during follow-up.

late-onset disorder
cancer predisposition
Duchenne muscular dystrophy


Cerebral infarction in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked form of muscular dystrophy characterized by progressive limb-girdle distribution of muscle weakness. Morbidity related to cardiomyopathy (CMO) is common, but cerebral infarction (CI) is relatively rare in these patients. We report a case of a pontine infarct in a patient with DMD and advanced CMO, and review the published data on CMO and CI in patients with DMD.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked
    GENETICS

    form of muscular dystrophy
    DIAGNOSIS

 characterized by

    progressive limb-girdle distribution of muscle weakness
    SYMPTOMS

.

    Morbidity
    SYMPTOMS

 related to

    cardiomyopathy (CMO)
    DIAGNOSIS

 is common, but

    cerebral infarction (CI)
    SYMPTOMS

 is relatively rare in these patients. We report a case of a

    pontine infarct
    SYMPTOMS

 in a patient with

    DMD
    DIAGNOSIS

 and

    advanced CMO
    DIAGNOSIS

, and review the published data on

    CMO
    DIAGNOSIS

 and

    CI
    SYMPTOMS

 in patients with

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
form of muscular dystrophy
cardiomyopathy (CMO)
DMD
advanced CMO
CMO
DMD


Tracheotomy bleeding from an unusual tracheo-arterial fistula: involvement of an aberrant right subclavian artery.

The development of a tracheo-arterial fistula is a rare but severe complication of tracheotomy. The reported patient presented with such a fistula involving an aberrant right subclavian artery, termed an arteria lusoria, an aortic arch abnormality which is usually asymptomatic.

A 30-year-old man was admitted to our institution for bleeding through his tracheotomy. He had been treated for advanced Duchenne muscular dystrophy, involving invasive assisted ventilation, since the age of 10 years. Surgical exploration and computed tomography scanning revealed a tracheo-arterial fistula involving an aberrant right subclavian artery, associated with severe scoliosis. Emergency, transient haemostasis was achieved by over-inflation of the tracheostomy tube cuff. Aneurysm ablation was successfully achieved as the result of an endovascular interventional radiology procedure.

Arteria lusoria is one of the most common aortic arch abnormalities. The occurrence of an aneurysm of this artery in a tracheotomised patient has not previously been described. In Duchenne muscular dystrophy patients, spinal deformities may result in thoracic compression, which may alter the anatomical relations of mediastinal vessels. Such deformities are slowly progressive. Thus, vigilance is required in the long term management of Duchenne muscular dystrophy patients with a tracheostomy.

The development of a

    tracheo-arterial fistula
    SYMPTOMS

 is a rare but severe complication of

    tracheotomy
    MEDICATION

. The reported patient presented with such a

    fistula involving an aberrant right subclavian artery, termed an arteria lusoria
    SYMPTOMS

, an

    aortic arch abnormality
    SYMPTOMS

 which is usually

    asymptomatic
    NEG_FINDINGS

.

A

    30-year-old
    AGE

    man
    GENDER

 was admitted to our institution for

    bleeding through his tracheotomy
    SYMPTOMS

.

    He
    GENDER

 had been treated for

    advanced Duchenne muscular dystrophy
    DIAGNOSIS

, involving

    invasive assisted ventilation
    MEDICATION

,

    since the age of 10 years
    AGE

.

    Surgical exploration
    PARACLINICAL

 and

    computed tomography scanning
    PARACLINICAL

 revealed a

    tracheo-arterial fistula involving an aberrant right subclavian artery
    SYMPTOMS

, associated with

    severe scoliosis
    SYMPTOMS

. Emergency,

    transient haemostasis
    MEDICATION

 was achieved by

    over-inflation of the tracheostomy tube cuff
    MEDICATION

.

    Aneurysm ablation
    MEDICATION

 was successfully achieved as the result of an

    endovascular interventional radiology procedure
    MEDICATION

.

    Arteria lusoria
    SYMPTOMS

 is one of the most common

    aortic arch abnormalities
    SYMPTOMS

. The occurrence of an

    aneurysm of this artery
    SYMPTOMS

 in a

    tracheotomised
    MEDICATION

 patient has not previously been described. In

    Duchenne muscular dystrophy
    DIAGNOSIS

 patients,

    spinal deformities
    SYMPTOMS

 may result in

    thoracic compression
    SYMPTOMS

, which may

    alter the anatomical relations of mediastinal vessels
    SYMPTOMS

.

    Such deformities
    SYMPTOMS

 are

    slowly progressive
    SYMPTOMS

. Thus, vigilance is required in the long term management of

    Duchenne muscular dystrophy
    DIAGNOSIS

 patients with a

    tracheostomy
    MEDICATION

.

advanced Duchenne muscular dystrophy
Duchenne muscular dystrophy
Duchenne muscular dystrophy


Aminotransferases and muscular diseases: a disregarded lesson. Case reports and review of the literature.

The aim of this study was to call the attention to the often disregarded message that hypertransaminasemia may be a marker of both liver and muscle diseases by presenting personal case reports and a systematic literature review. Three male children (mean age 5.7 years) were inappropriately addressed, during the last 12 months, to our paediatric liver unit for diagnostic work-up of a chronic hypertransaminasemia of unknown origin. In one of them, a liver biopsy had already been performed. On admission, physical examination, evaluation of serum levels of creatine kinase, and dystrophin genetic testing finally led to a diagnosis of muscular dystrophy. One hundred fourteen similar cases, 21 with unnecessary liver biopsy, were found by Medline search. Expensive and invasive tests planned to investigate liver diseases should be postponed until alternative sources of increased serum aminotransferases, primarily myopathic injury, have been excluded.

The aim of this study was to call the attention to the often disregarded message that

    hypertransaminasemia
    BIOCHEMICAL

 may be a marker of both

    liver and muscle diseases
    DIAGNOSIS

 by presenting personal case reports and a systematic literature review. Three

    male
    GENDER

    children
    AGE

 (

    mean age 5.7 years
    AGE

) were inappropriately addressed, during the last 12 months, to our

    paediatric liver unit
    PARACLINICAL

 for

    diagnostic work-up
    PARACLINICAL

 of a

    chronic hypertransaminasemia of unknown origin
    BIOCHEMICAL

. In one of them, a

    liver biopsy
    PARACLINICAL

 had already been performed. On admission,

    physical examination
    PARACLINICAL

,

    evaluation of serum levels of creatine kinase
    PARACLINICAL

, and

    dystrophin genetic testing
    PARACLINICAL

 finally led to a diagnosis of

    muscular dystrophy
    DIAGNOSIS

. One hundred fourteen similar cases, 21 with unnecessary

    liver biopsy
    PARACLINICAL

, were found by Medline search. Expensive and invasive tests planned to investigate

    liver diseases
    DIAGNOSIS

 should be postponed until alternative sources of

    increased serum aminotransferases
    BIOCHEMICAL

, primarily

    myopathic injury
    NEG_FINDINGS

, have been excluded.

liver and muscle diseases
muscular dystrophy
liver diseases


Detection of focal cerebral injury using diffusion tensor magnetic resonance imaging in a boy with becker muscular dystrophy.

Here, we report on a boy affected by both cerebral palsy and Becker muscular dystrophy (BMD). He had infrequently used his right hand since birth. But brain magnetic resonance imaging (MRI) taken at the age of 15 months showed no specific finding. Approximately 1 month later, muscle enzymes of his older brother were incidentally found to be elevated. The patient and his brother were diagnosed with progressive muscular dystrophy by gene analysis. At the age of 6 years, he underwent orthopedic surgery due to a right equinovarus deformity and BMD was confirmed by concomitant muscle biopsy. During the post-operative rehabilitation, clumsiness of the right hand was also observed. A follow-up brain MRI with diffusion tensor imaging (DTI) was taken. Although no responsible lesion was found on conventional MRI, DTI and fiber tractography revealed a decrease in the quantity of fibers in the left corticospinal tract. He was additionally diagnosed as having cerebral palsy.

Here, we report on a

    boy
    GENDER

 affected by both

    cerebral palsy
    SYMPTOMS

 and

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

.

    He
    GENDER

 had

    infrequently used his right hand
    NEG_FINDINGS

 since

    birth
    AGE

. But

    brain magnetic resonance imaging (MRI)
    PARACLINICAL

 taken at the

    age of 15 months
    AGE

 showed

    no specific finding
    NEG_FINDINGS

. Approximately 1 month later,

    muscle enzymes of his older brother
    BIOCHEMICAL

 were incidentally found

    to be elevated
    BIOCHEMICAL

. The patient and

    his brother
    GENDER

 were diagnosed with

    progressive muscular dystrophy
    DIAGNOSIS

 by

    gene analysis
    PARACLINICAL

. At the

    age of 6 years
    AGE

,

    he
    GENDER

 underwent

    orthopedic surgery
    MEDICATION

 due to a

    right equinovarus deformity
    SYMPTOMS

 and

    BMD
    DIAGNOSIS

 was confirmed by

    concomitant muscle biopsy
    PARACLINICAL

. During the

    post-operative rehabilitation
    MEDICATION

,

    clumsiness of the right hand
    SYMPTOMS

 was also observed. A

    follow-up brain MRI with diffusion tensor imaging (DTI)
    PARACLINICAL

 was taken. Although

    no responsible lesion was found on conventional MRI
    NEG_FINDINGS

,

    DTI
    PARACLINICAL

 and

    fiber tractography
    PARACLINICAL

 revealed a

    decrease in the quantity of fibers in the left corticospinal tract
    SYMPTOMS

.

    He
    GENDER

 was additionally diagnosed as having

    cerebral palsy
    DIAGNOSIS

.

Becker muscular dystrophy (BMD)
progressive muscular dystrophy
BMD
cerebral palsy

muscle enzymes of his older brother
to be elevated

orthopedic surgery
post-operative rehabilitation


9 year old girl with progressive weakness.

A 9-year-old female patient experienced progressive weakness and myalgias of shoulders and back of several months duration. Her medical history was notable for spina bifida in association with a Chiari type II malformation and hydrocephalus. Developmental motor milestones were delayed whereby walking began at age 2. She had mild bowel and bladder dysfunction. At presentation, her neurological exam was notable for weak shoulder adduction, hip and knee flexion and she demonstrated a partial Gower's maneuver. A muscle biopsy showed dystrophic changes and immunohistochemical findings of a Duchenne's mosaic which was confirmed by DNA analysis. The proposed pathogenesis in this case is unfavourable lyonization, which was corroborated by X-inactivation studies.

A

    9-year-old
    AGE

    female
    GENDER

 patient experienced

    progressive weakness
    SYMPTOMS

 and

    myalgias of shoulders and back of several months duration
    SYMPTOMS

.

    Her
    GENDER

 medical history was notable for

    spina bifida
    DIAGNOSIS

 in association with a

    Chiari type II malformation
    DIAGNOSIS

 and

    hydrocephalus
    DIAGNOSIS

.

    Developmental motor milestones were delayed
    SYMPTOMS

 whereby

    walking began
    SYMPTOMS

 at

    age 2
    AGE

.

    She
    GENDER

 had

    mild bowel and bladder dysfunction
    SYMPTOMS

. At presentation,

    her
    GENDER

    neurological exam
    PARACLINICAL

 was notable for

    weak shoulder adduction, hip and knee flexion
    SYMPTOMS

 and

    she
    GENDER

 demonstrated a

    partial Gower's maneuver
    SYMPTOMS

. A

    muscle biopsy
    PARACLINICAL

 showed

    dystrophic changes
    MICROSCOPIC

 and

    immunohistochemical findings of a Duchenne's mosaic
    SYMPTOMS

 which was confirmed by

    DNA analysis
    PARACLINICAL

. The proposed pathogenesis in this case is

    unfavourable lyonization
    GENETICS

, which was corroborated by

    X-inactivation studies
    PARACLINICAL

.

spina bifida
Chiari type II malformation
hydrocephalus


Drug rash, eosinophilia, and systemic symptoms syndrome: Two pediatric cases demonstrating the range of severity in presentation--A case of vancomycin-induced drug hypersensitivity mimicking toxic shock syndrome and a milder case induced by minocycline.

Drug rash, eosinophilia, and systemic symptoms syndrome is a type of drug hypersensitivity reaction characterized by the clinical triad of skin eruption, fever, and internal organ involvement. Drug rash, eosinophilia, and systemic symptoms syndrome has rarely been reported in association with vancomycin or in the pediatric population. There have only been four pediatric case reports of drug rash, eosinophilia, and systemic symptoms syndrome and three cases of drug rash, eosinophilia, and systemic symptoms syndrome involving vancomycin published in the English literature to date.

We describe two pediatric cases of drug rash, eosinophilia, and systemic symptoms syndrome to illustrate the range in severity of presentation. The first case illustrates drug rash, eosinophilia, and systemic symptoms syndrome associated with vancomycin exposure in a 14-yr-old boy with Duchenne muscular dystrophy after posterior spinal fusion, whose clinical presentation was indistinguishable from toxic shock syndrome. The second case illustrates a milder and more typical presentation of drug rash, eosinophilia, and systemic symptoms syndrome in a 14-yr-old boy being treated with minocycline for acne. We also present a review of the literature relevant to this syndrome.

: Drug rash, eosinophilia, and systemic symptoms syndrome is relatively unknown among general pediatricians and pediatric intensivists and may potentially become more common with the increasing use of long-term medications in the pediatric population. Our cases demonstrate the importance of an awareness of drug rash, eosinophilia, and systemic symptoms syndrome among general pediatricians and pediatric intensivists because drug rash, eosinophilia, and systemic symptoms syndrome may present in any range of severity, from indolent illness to frank and refractory shock.

    Drug rash, eosinophilia, and systemic symptoms syndrome
    DIAGNOSIS

 is a type of

    drug hypersensitivity reaction
    DIAGNOSIS

 characterized by the clinical triad of

    skin eruption
    SYMPTOMS

,

    fever
    SYMPTOMS

, and

    internal organ involvement
    SYMPTOMS

.

    Drug rash
    DIAGNOSIS

,

    eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 has rarely been reported in association with

    vancomycin
    MEDICATION

 or in the

    pediatric
    AGE

 population. There have only been four

    pediatric
    AGE

 case reports of

    drug rash
    DIAGNOSIS

,

    eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 and three cases of

    drug rash, eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 involving

    vancomycin
    DIAGNOSIS

 published in the English literature to date.

We describe two

    pediatric
    AGE

 cases of

    drug rash
    DIAGNOSIS

,

    eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 to illustrate the range in severity of presentation. The first case illustrates

    drug rash, eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 associated with

    vancomycin exposure
    MEDICATION

 in a

    14-yr-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 after

    posterior spinal fusion
    MEDICATION

, whose clinical presentation was indistinguishable from

    toxic shock syndrome
    DIAGNOSIS

. The second case illustrates a milder and more typical presentation of

    drug rash, eosinophilia, and systemic symptoms syndrome
    SYMPTOMS

 in a

    14-yr-old
    AGE

    boy
    GENDER

 being

    treated with minocycline
    MEDICATION

 for

    acne
    DIAGNOSIS

. We also present a review of the literature relevant to this syndrome.

:

    Drug rash
    DIAGNOSIS

,

    eosinophilia
    SYMPTOMS

, and

    systemic symptoms syndrome
    SYMPTOMS

 is relatively unknown among general pediatricians and

    pediatric intensivists
    PARACLINICAL

 and may potentially become more common with the increasing use of

    long-term medications
    MEDICATION

 in the

    pediatric
    AGE

 population. Our cases demonstrate the importance of an awareness of

    drug rash
    DIAGNOSIS

,

    eosinophilia
    SYMPTOMS

, and

    systemic symptoms syndrome
    SYMPTOMS

 among

    general pediatricians
    PARACLINICAL

 and

    pediatric intensivists
    PARACLINICAL

 because

    drug rash
    DIAGNOSIS

,

    eosinophilia
    SYMPTOMS

, and

    systemic symptoms syndrome
    SYMPTOMS

 may present in any range of severity, from

    indolent illness
    SYMPTOMS

 to

    frank and refractory shock
    SYMPTOMS

.

vancomycin
vancomycin exposure
posterior spinal fusion
treated with minocycline
long-term medications


Marked hemiatrophy in carriers of Duchenne muscular dystrophy.

To describe the clinical and molecular genetic findings in 2 carriers of Duchenne muscular dystrophy (DMD) who exhibited marked hemiatrophy. Duchenne muscular dystrophy is an X-linked disorder in which affected male patients harbor mutations in the dystrophin gene. Female patients with heterozygous mutations may be manifesting carriers.

Case study.

Neurology clinic.

Two manifesting carriers of DMD.

Clinical and radiologic examinations along with histologic and molecular investigations.

Both patients had marked right-sided hemiatrophy on examination with radiologic evidence of muscle atrophy and fatty replacement on the affected side. In each case, histologic analysis revealed a reduction in dystrophin staining on the right side. Genetic analysis of the dystrophin gene revealed a tandem exonic duplication in patient 1 and a multiexonic deletion in patient 2 with no further point mutations identified on the other chromosome.

Marked hemiatrophy can occur in DMD manifesting carriers. This is likely to result from a combination of skewed X-inactivation and somatic mosaicism.

To describe the clinical and molecular genetic findings in 2 carriers of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 who exhibited

    marked hemiatrophy
    SYMPTOMS

.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is an

    X-linked disorder
    GENETICS

 in which affected

    male
    GENDER

 patients harbor

    mutations in the dystrophin gene
    GENETICS

.

    Female
    GENDER

 patients with

    heterozygous mutations
    GENETICS

 may be manifesting carriers.

    Neurology clinic
    PARACLINICAL

.

    Two manifesting carriers of DMD
    FAMILY

.

    Clinical and radiologic examinations along with histologic and molecular investigations
    PARACLINICAL

.

Both patients had

    marked right-sided hemiatrophy
    SYMPTOMS

 on examination with

    radiologic evidence of muscle atrophy and fatty replacement on the affected side
    SYMPTOMS

. In each case,

    histologic analysis
    PARACLINICAL

 revealed a

    reduction in dystrophin staining on the right side
    SYMPTOMS

.

    Genetic analysis of the dystrophin gene
    PARACLINICAL

 revealed a

    tandem exonic duplication
    GENETICS

 in patient 1 and

    a multiexonic deletion
    GENETICS

 in patient 2 with

    no further point mutations identified on the other chromosome
    NEG_FINDINGS

.

    Marked hemiatrophy
    SYMPTOMS

 can occur in

    DMD
    DIAGNOSIS

 manifesting carriers. This is likely to result from a combination of

    skewed X-inactivation
    GENETICS

 and

    somatic mosaicism
    GENETICS

.

Duchenne muscular dystrophy (DMD)
Duchenne muscular dystrophy
DMD

X-linked disorder
mutations in the dystrophin gene
heterozygous mutations
tandem exonic duplication
a multiexonic deletion
skewed X-inactivation
somatic mosaicism


Episodic myoglobinuria in a primary gamma-sarcoglycanopathy.

Episodic myoglobinuria is a well-recognized complication of metabolic myopathies, and may occur in Duchenne and Becker dystrophies, but has only rarely been associated with limb-girdle muscular dystrophy. We describe an unusual presentation, with rhabdomyolysis, of limb-girdle muscular dystrophy (LGMD). We evaluated a patient for progressive muscle weakness and tenderness, with myoglobinuria one week after initial presentation. Immunohistochemistry on muscle tissue revealed absent staining for gamma-sarcoglycan, confirmed by detection of a homozygous mutation in the gamma-sarcoglycan gene. Myoglobinuria has been previously reported only twice in LGMD. It is therefore important to recognize that myoglobinuria may be a symptom of a muscular dystrophy, and muscle biopsy and immunostaining are important tools for diagnosis.

    Episodic myoglobinuria
    BIOCHEMICAL

 is a well-recognized complication of

    metabolic myopathies
    DIAGNOSIS

, and may occur in

    Duchenne
    DIAGNOSIS

 and

    Becker dystrophies
    DIAGNOSIS

, but has only rarely been associated with

    limb-girdle muscular dystrophy
    DIAGNOSIS

. We describe an unusual presentation, with

    rhabdomyolysis
    SYMPTOMS

, of

    limb-girdle muscular dystrophy (LGMD)
    DIAGNOSIS

. We evaluated a patient for

    progressive muscle weakness and tenderness
    SYMPTOMS

, with

    myoglobinuria
    BIOCHEMICAL

 one week after initial presentation.

    Immunohistochemistry on muscle tissue
    PARACLINICAL

 revealed

    absent staining for gamma-sarcoglycan
    BIOCHEMICAL

, confirmed by detection of a

    homozygous mutation in the gamma-sarcoglycan gene
    GENETICS

.

    Myoglobinuria
    BIOCHEMICAL

 has been previously reported only twice in

    LGMD
    DIAGNOSIS

. It is therefore important to recognize that

    myoglobinuria
    BIOCHEMICAL

 may be a symptom of a

    muscular dystrophy
    DIAGNOSIS

, and

    muscle biopsy
    PARACLINICAL

 and

    immunostaining
    PARACLINICAL

 are important tools for diagnosis.

Episodic myoglobinuria
myoglobinuria
absent staining for gamma-sarcoglycan
Myoglobinuria
myoglobinuria

metabolic myopathies
Duchenne
Becker dystrophies
limb-girdle muscular dystrophy
limb-girdle muscular dystrophy (LGMD)
LGMD
muscular dystrophy


Perioperative cardiac arrest in a patient with previously undiagnosed Becker's muscular dystrophy after isoflurane anaesthesia for elective surgery.

A previously fit 12-yr-old boy, who had no previous history of anaesthesia, underwent general anaesthesia using isoflurane for an elective circumcision. After uneventful surgery and anaesthesia, he suffered a cardiorespiratory arrest in the recovery room. Prompt oxygenation and cardiopulmonary resuscitation (CPR) were instituted. The initial serum potassium was >13 mmol litre(-1) and prolonged CPR was required while potassium levels were reduced. Further investigation demonstrated a creatine kinase (CK) >70 000 U litre(-1) which was consistent with a diagnosis of rhabdomyolysis. Despite requiring CPR for 1 h 45 min and a prolonged intensive care admission for multi-organ failure, the child has made an excellent recovery, including normal cognitive function. Subsequent genetic analysis has shown that the boy has previously undiagnosed Becker's muscular dystrophy. We believe that the patient had acute rhabdomyolysis as a result of a volatile anaesthetic agent in association with an undiagnosed muscular dystrophy. In recent years, largely based on case report literature, there has been a shift in opinion as to the cause of such adverse perioperative events. What was previously thought to be malignant hyperpyrexia (MH) is now considered to be anaesthesia-induced rhabdomyolysis, an alternative and distinct reaction. The distinguishing feature of anaesthesia-induced rhabdomyolysis from MH is an acute rhabdomyolysis, without preceding hypermetabolism.

A previously fit

    12-yr-old
    AGE

    boy
    GENDER

, who had

    no previous history of anaesthesia
    NEG_FINDINGS

, underwent

    general anaesthesia using isoflurane for an elective circumcision
    MEDICATION

. After

    uneventful surgery and anaesthesia
    MEDICATION

,

    he
    GENDER

 suffered a

    cardiorespiratory arrest
    SYMPTOMS

 in the recovery room.

    Prompt oxygenation and cardiopulmonary resuscitation (CPR)
    MEDICATION

 were instituted. The

    initial serum potassium was >13 mmol litre(-1)
    BIOCHEMICAL

 and

    prolonged CPR
    MEDICATION

 was required while

    potassium levels were reduced
    BIOCHEMICAL

. Further investigation demonstrated a

    creatine kinase (CK) >70 000 U litre(-1)
    BIOCHEMICAL

 which was consistent with a diagnosis of

    rhabdomyolysis
    DIAGNOSIS

. Despite

    requiring CPR for 1 h 45 min and a prolonged intensive care admission
    MEDICATION

 for

    multi-organ failure
    SYMPTOMS

, the

    child
    AGE

 has made an

    excellent recovery
    SYMPTOMS

, including

    normal cognitive function
    NEG_FINDINGS

. Subsequent

    genetic analysis
    PARACLINICAL

 has shown that the

    boy
    GENDER

 has previously undiagnosed

    Becker's muscular dystrophy
    DIAGNOSIS

. We believe that the patient had

    acute rhabdomyolysis
    DIAGNOSIS

 as a result of a

    volatile anaesthetic agent
    MEDICATION

 in association with an

    undiagnosed muscular dystrophy
    DIAGNOSIS

. In recent years, largely based on case report literature, there has been a shift in opinion as to the cause of such

    adverse perioperative events
    SYMPTOMS

. What was previously thought to be

    malignant hyperpyrexia (MH)
    DIAGNOSIS

 is now considered to be

    anaesthesia-induced rhabdomyolysis
    DIAGNOSIS

, an alternative and distinct reaction. The distinguishing feature of

    anaesthesia-induced rhabdomyolysis
    DIAGNOSIS

 from

    MH
    DIAGNOSIS

 is an

    acute rhabdomyolysis
    SYMPTOMS

,

    without preceding hypermetabolism
    NEG_FINDINGS

.

no previous history of anaesthesia
normal cognitive function
without preceding hypermetabolism

cardiorespiratory arrest
multi-organ failure
excellent recovery
adverse perioperative events
acute rhabdomyolysis

rhabdomyolysis
Becker's muscular dystrophy
acute rhabdomyolysis
undiagnosed muscular dystrophy
malignant hyperpyrexia (MH)
anaesthesia-induced rhabdomyolysis
anaesthesia-induced rhabdomyolysis
MH


Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients.

Theoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated skipping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with Becker muscular dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their internally deleted, but essentially functional, dystrophins are identical to those that are expected as end products in DMD patients treated with the exon 51 skipping therapy. The mild phenotype encourages further development of exon 51 skipping therapy.

Theoretically, 13% of patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 may benefit from

    antisense-mediated skipping of exon 51 to restore the reading frame
    MEDICATION

, which results in the production of a

    shortened dystrophin protein
    BIOCHEMICAL

. We give a detailed description with longitudinal follow up of three patients with

    Becker muscular dystrophy
    DIAGNOSIS

 with

    in-frame deletions in the DMD gene encompassing exon 51
    GENETICS

. Their

    internally deleted, but essentially functional, dystrophins are identical to those that
    SYMPTOMS

 are expected as end products in

    DMD
    DIAGNOSIS

 patients treated with the

    exon 51 skipping therapy
    MEDICATION

. The mild phenotype encourages further development of

    exon 51 skipping therapy
    MEDICATION

.

Duchenne muscular dystrophy
Becker muscular dystrophy
DMD


The diagnostic difficulties of complex glycerol kinase deficiency.

We describe 2 siblings with the contiguous X-linked gene deletion syndrome, complex glycerol kinase deficiency. The elder sibling demonstrated the difficulties diagnosing this rare condition. Affected children have the combined complications of congenital adrenal hypoplasia, Duchenne muscular dystrophy, and glycerol kinase deficiency. These patients illustrate the importance of genetic testing and prepregnancy counseling. In addition, they demonstrate the need for a multidisciplinary team approach in their management.

We describe 2 siblings with the

    contiguous X-linked gene deletion syndrome
    GENETICS

,

    complex glycerol kinase deficiency
    DIAGNOSIS

. The

    elder sibling
    AGE

 demonstrated the difficulties diagnosing this rare condition. Affected

    children
    AGE

 have the combined complications of

    congenital adrenal hypoplasia
    SYMPTOMS

,

    Duchenne muscular dystrophy
    DIAGNOSIS

, and

    glycerol kinase deficiency
    BIOCHEMICAL

. These patients illustrate the importance of

    genetic testing
    PARACLINICAL

 and

    prepregnancy counseling
    MEDICATION

. In addition, they demonstrate the need for a

    multidisciplinary team approach
    MEDICATION

 in their management.

complex glycerol kinase deficiency
Duchenne muscular dystrophy

prepregnancy counseling
multidisciplinary team approach


Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacort.

Two siblings were evaluated for progressive proximal weakness and elevated creatine kinase. Immunohistochemical staining in the brother's muscle biopsy showed near absence of all four sarcoglycan subunits. Clinical progression prompted a trial of deflazacort in both siblings. At 22 months of drug therapy, both patients have stable or improved strength testing. Further analysis on the muscle biopsy revealed homozygous beta-sarcoglycan gene mutation (S114F), consistent with the limb-girdle muscular dystrophy type 2E (LGME 2E). Despite the severe phenotype, deflazacort has a beneficial effect on slowing disease progression in LGME 2E similar to that seen in Duchenne muscular dystrophy.

Two siblings were evaluated for

    progressive proximal weakness
    SYMPTOMS

 and

    elevated creatine kinase
    BIOCHEMICAL

.

    Immunohistochemical staining in the brother's muscle biopsy
    PARACLINICAL

 showed

    near absence of all four sarcoglycan subunits
    BIOCHEMICAL

.

    Clinical progression
    SYMPTOMS

 prompted a

    trial of deflazacort
    MEDICATION

 in both siblings. At

    22 months of drug therapy
    MEDICATION

, both patients have

    stable or improved strength testing
    SYMPTOMS

. Further

    analysis on the muscle biopsy
    PARACLINICAL

 revealed

    homozygous beta-sarcoglycan gene mutation (S114F)
    GENETICS

, consistent with the

    limb-girdle muscular dystrophy type 2E (LGME 2E)
    DIAGNOSIS

. Despite the severe phenotype,

    deflazacort
    MEDICATION

 has a beneficial effect on

    slowing disease progression
    SYMPTOMS

 in

    LGME 2E
    DIAGNOSIS

 similar to that seen in

    Duchenne muscular dystrophy
    DIAGNOSIS

.

progressive proximal weakness
Clinical progression
stable or improved strength testing
slowing disease progression

trial of deflazacort
22 months of drug therapy
deflazacort


Rapid and powerful decaplex and dodecaplex PGD protocols for Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive disorder, resulting from deletions, duplications and point mutations in the dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis (PGD) still remain challenging due to the enormous size of the gene and the high risk of intragenic recombination, limitations that often lead to sex determination and selection of female embryos. This study describes direct and rapid decaplex and dodecaplex polymerase chain reaction protocols enabling the analysis of five or seven exons and four microsatellite markers scattered along the dystrophin gene, chosen to be located in the two deletion hotspots, and the analysis of amelogenin sequences for gender determination. The dodecaplex protocol may be applied to most of the couples requesting PGD for DMD in whom the female partner is a carrier of a deletion. This generic approach will allow prompt response to the PGD referrals by reducing the pre-clinical PGD work-up. It was successfully applied in three DMD families, resulting in the birth of a girl as well as in a healthy ongoing pregnancy.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a common

    childhood lethal X-linked recessive disorder
    GENETICS

, resulting from

    deletions, duplications and point mutations in the dystrophin gene
    GENETICS

.

    Single-cell protocols for preimplantation genetic diagnosis (PGD)
    PARACLINICAL

 still remain challenging due to the enormous size of the gene and the high risk of

    intragenic recombination
    GENETICS

, limitations that often lead to

    sex
    NEG_FINDINGS

 determination and selection of

    female embryos
    MEDICATION

. This study describes

    direct and rapid decaplex and dodecaplex polymerase chain reaction
    PARACLINICAL

 protocols enabling the

    analysis of five or seven exons and four microsatellite markers scattered along the dystrophin gene
    PARACLINICAL

, chosen to be located

    in the two deletion hotspots
    GENETICS

, and the

    analysis of amelogenin sequences
    PARACLINICAL

 for

    gender determination
    PARACLINICAL

. The

    dodecaplex protocol
    PARACLINICAL

 may be applied to most of the

    couples
    GENDER

 requesting

    PGD
    MEDICATION

 for

    DMD
    DIAGNOSIS

 in whom the

    female partner is a carrier of a deletion
    FAMILY

. This generic approach will allow prompt response to the

    PGD referrals
    MEDICATION

 by

    reducing the pre-clinical PGD work-up
    MEDICATION

. It was successfully applied in three

    DMD
    DIAGNOSIS

 families, resulting in the birth of a

    girl
    MEDICATION

 as well as in a

    healthy ongoing pregnancy
    MEDICATION

.

Duchenne muscular dystrophy (DMD)
DMD
DMD

female embryos
PGD
PGD referrals
reducing the pre-clinical PGD work-up
girl
healthy ongoing pregnancy


Coinheritance of Noonan syndrome and Becker muscular dystrophy.

We describe for the first time a case of a 9-year old boy with co-existence of dystrophinopathy and Noonan syndrome (NS). Although the patient has a severe muscular clinical phenotype, consistent with Duchenne muscular dystrophy (DMD), the diagnosis of Becker muscular dystrophy (BMD) was proposed based on family history (brother with BMD) and confirmed by muscle immunohistochemistry, and molecular study shown an in-frame DMD gene mutation. The patient also fulfilled the clinical criteria of NS and he harbors a hotspot mutation on PTPN11 gene. This genetic combination may be an explanation for the variability of clinical expression in the family.

We describe for the first time a case of a

    9-year old
    AGE

    boy
    GENDER

 with

    co-existence of dystrophinopathy
    FAMILY

    and Noonan syndrome (NS)
    DIAGNOSIS

. Although the patient has a

    severe muscular clinical phenotype
    SYMPTOMS

, consistent with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, the diagnosis of

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 was proposed based on

    family history (brother with BMD)
    FAMILY

 and confirmed by

    muscle immunohistochemistry
    PARACLINICAL

, and

    molecular study
    PARACLINICAL

 shown an

    in-frame DMD gene mutation
    GENETICS

. The patient also fulfilled the clinical criteria of

    NS
    DIAGNOSIS

 and

    he
    GENDER

 harbors a

    hotspot mutation on PTPN11 gene
    GENETICS

. This

    genetic combination
    GENETICS

 may be an explanation for the variability of clinical expression in the family.

and Noonan syndrome (NS)
Duchenne muscular dystrophy (DMD)
Becker muscular dystrophy (BMD)
NS

in-frame DMD gene mutation
hotspot mutation on PTPN11 gene
genetic combination


Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and efficient recovery from profound neuromuscular block was achieved, and no adverse events or other safety concerns were observed.

A case is reported in which a

    child
    AGE

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 received a

    dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block
    MEDICATION

.

    Sugammadex
    MEDICATION

 is the first

    selective relaxant binding agent
    MEDICATION

 and

    reverses rocuronium- and vecuronium-induced neuromuscular block
    MEDICATION

. A

    fast and efficient recovery from profound neuromuscular block
    SYMPTOMS

 was achieved, and

    no adverse events or other safety concerns
    NEG_FINDINGS

 were observed.


[Contiguous gene deletion syndrome in Xp21: an unusual form of presentation].

We report a case of an infant where the association of Duchenne's muscular dystrophy (DMD) and pseudohypertriglyceridaemia led to the diagnosis of contiguous gene deletion syndrome in Xp21.

A 7-month-old male infant who was referred due to psychomotor retardation. The examination revealed pronounced axial hypotonia. Lab findings showed high levels of muscular enzymes with creatine phosphokinase levels of 12,829 IU/L, together with high blood levels of triglycerides. Electromyogram findings were consistent with myopathic compromise. The genetic study for dystrophinopathies revealed the existence of a deletion in the dystrophin gene. Further lab findings identified high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency. The genetic study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, the glycerol kinase deficiency, the congenital adrenal hypoplasia (gene DAX1) and mental retardation (gene IL1RAPL1).

In infants and small children with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia it is essential to take into account contiguous gene deletion syndrome in Xp21 to be able to prevent and treat the metabolic complications arising from adrenal hypoplasia.

We report a case of an

    infant
    AGE

 where the association of

    Duchenne's muscular dystrophy (DMD)
    DIAGNOSIS

 and

    pseudohypertriglyceridaemia
    BIOCHEMICAL

 led to the diagnosis of

    contiguous gene deletion syndrome in Xp21
    GENETICS

.

A

    7-month-old
    AGE

    male
    GENDER

    infant
    AGE

 who was referred due to

    psychomotor retardation
    SYMPTOMS

. The examination revealed

    pronounced axial hypotonia
    SYMPTOMS

.

    Lab findings
    PARACLINICAL

 showed

    high levels of muscular enzymes with creatine phosphokinase levels of 12,829 IU/L
    BIOCHEMICAL

, together with

    high blood levels of triglycerides
    BIOCHEMICAL

.

    Electromyogram findings
    PARACLINICAL

 were consistent with

    myopathic compromise
    DIAGNOSIS

. The

    genetic study
    PARACLINICAL

 for

    dystrophinopathies
    DIAGNOSIS

 revealed the existence of a

    deletion in the dystrophin gene
    GENETICS

. Further

    lab findings
    PARACLINICAL

 identified

    high glycerol concentrations both in blood and in urine
    BIOCHEMICAL

 that were compatible with a

    glycerol kinase deficiency
    BIOCHEMICAL

. The

    genetic study
    PARACLINICAL

 confirmed the existence of a

    deletion in Xp21 of the genes responsible for DMD
    GENETICS

, the

    glycerol kinase deficiency
    BIOCHEMICAL

, the

    congenital adrenal hypoplasia
    SYMPTOMS

 (

    gene DAX1)
    GENETICS

 and

    mental retardation
    SYMPTOMS

 (

    gene IL1RAPL1)
    GENETICS

.

In

    infants
    AGE

 and

    small children
    AGE

 with

    myopathic compromise
    SYMPTOMS

,

    increased levels of creatine phosphokinase
    BIOCHEMICAL

 and

    pseudohypertriglyceridaemia
    BIOCHEMICAL

 it is essential to take into account

    contiguous gene deletion syndrome in Xp21
    GENETICS

 to be able to prevent and treat the

    metabolic complications
    SYMPTOMS

 arising from

    adrenal hypoplasia
    SYMPTOMS

.

Duchenne's muscular dystrophy (DMD)
myopathic compromise
dystrophinopathies

psychomotor retardation
pronounced axial hypotonia
congenital adrenal hypoplasia
mental retardation
myopathic compromise
metabolic complications
adrenal hypoplasia


Cardiovascular magnetic resonance reveals similar damage to the heart of patients with Becker and limb-girdle muscular dystrophy but no cardiac symptoms.

Cardiac involvement in patients with a sarcoglycanopathy (limb-girdle muscular dystrophy) has been described previously; however, this is the first cardiovascular magnetic resonance (CMR) study in such a patient demonstrating an interesting pattern of myocardial damage using late gadolinium enhancement (LGE) imaging. Moreover, the wall motion abnormality and the subepicardial pattern of LGE in this patient with a sarcoglycanopathy is in agreement with the findings in another patient with Becker muscular dystrophy. The predominance of LGE in the subepicardial layers of the left ventricular inferolateral wall suggests that such a myocardial damage pattern represents a nonspecific cardiac phenotype in response to exaggerated mechanical stress in this region, at least in patients with a sarcoglycanopathy or dystrophinopathy.

    Cardiac involvement
    SYMPTOMS

 in patients with a

    sarcoglycanopathy
    DIAGNOSIS

 (

    limb-girdle muscular dystrophy)
    DIAGNOSIS

 has been described previously; however, this is the first

    cardiovascular magnetic resonance (CMR)
    PARACLINICAL

 study in such a patient demonstrating an

    interesting pattern of myocardial damage
    SYMPTOMS

 using

    late gadolinium enhancement (LGE) imaging
    PARACLINICAL

. Moreover, the

    wall motion abnormality and the subepicardial pattern of LGE
    SYMPTOMS

 in this patient with a

    sarcoglycanopathy
    DIAGNOSIS

 is in agreement with the findings in another patient with

    Becker muscular dystrophy
    DIAGNOSIS

. The

    predominance of LGE in the subepicardial layers of the left ventricular inferolateral wall
    SYMPTOMS

 suggests that such a

    myocardial damage pattern
    SYMPTOMS

 represents a

    nonspecific cardiac phenotype
    SYMPTOMS

 in response to

    exaggerated mechanical stress in this
    SYMPTOMS

 region, at least in patients with a

    sarcoglycanopathy
    DIAGNOSIS

 or

    dystrophinopathy
    DIAGNOSIS

.

sarcoglycanopathy
limb-girdle muscular dystrophy)
sarcoglycanopathy
Becker muscular dystrophy
sarcoglycanopathy
dystrophinopathy


Congestive heart failure with rhabdomyolysis and acute renal failure in a manifesting female carrier of Duchenne muscular dystrophy with duplication of dystrophin gene.

We report a 69-year-old woman who presented with dyspnea, orthopnea, and acute renal failure. She also had proximal muscle weakness suggestive of muscle disease. Her symptoms were alleviated by induced dieresis, although there was high-serum creatine kinase. Investigations for any possible etiologies of rhabdomyolysis were all negative. An X-linked recessive muscle disease was highly suspicious in view of the fact that both of her sons had suffered from muscle disease and died of respiratory failure at the ages of 22 and 29, respectively. Her muscle biopsy showed mosaic pattern with dystrophin antibody against amino-terminal, carboxy-terminal, and rod domain. Her DNA study revealed heterozygous duplication at exon 1 to 6 of the dystrophin gene as well. Therefore, she is a manifesting carrier of dystrophinopathy who was first diagnosed in late adulthood with congestive heart failure, acute episode of spontaneous rhabdomyolysis, and acute renal failure.

We report a

    69-year-old
    AGE

    woman
    GENDER

 who presented with

    dyspnea
    SYMPTOMS

,

    orthopnea
    SYMPTOMS

, and

    acute renal failure
    SYMPTOMS

.

    She
    GENDER

 also had

    proximal muscle weakness
    SYMPTOMS

 suggestive of

    muscle disease
    DIAGNOSIS

.

    Her
    GENDER

 symptoms were alleviated by

    induced dieresis
    NEG_FINDINGS

, although there was

    high-serum creatine kinase
    BIOCHEMICAL

.

    Investigations for any possible etiologies of rhabdomyolysis
    NEG_FINDINGS

    were all negative
    NEG_FINDINGS

. An

    X-linked recessive muscle disease
    GENETICS

 was highly suspicious in view of the fact

    that both of her sons had suffered from muscle disease and died of respiratory failure at the ages of 22 and 29, respectively
    FAMILY

.

    Her
    GENDER

    muscle biopsy
    PARACLINICAL

 showed

    mosaic pattern
    MICROSCOPIC

    with dystrophin antibody against amino-terminal, carboxy-terminal, and rod domain
    BIOCHEMICAL

.

    Her
    GENDER

    DNA study
    PARACLINICAL

 revealed

    heterozygous duplication at exon 1 to 6 of the dystrophin gene as well
    GENETICS

. Therefore,

    she
    GENDER

 is a manifesting carrier of

    dystrophinopathy
    DIAGNOSIS

 who was first diagnosed in

    late adulthood
    AGE

 with

    congestive heart failure
    SYMPTOMS

,

    acute episode of spontaneous rhabdomyolysis
    SYMPTOMS

, and

    acute renal failure
    SYMPTOMS

.


Cardiac assessment of patients with Becker's muscular dystrophy.

Becker's muscular dystrophy (BMD) is one of the most common muscular dystrophy syndromes. The heart is always affected by myocardial fibrosis with early involvement of the right side. Traditionally, ECG, echocardiography and stress testing have been used to evaluate these patients. Cardiac MRI, offering superior assessment of the right side and visualization of the myocardial fibrosis could become the preferred imaging modality for evaluating patients with BMD.

    Becker's muscular dystrophy (BMD)
    DIAGNOSIS

 is one of the most common

    muscular dystrophy syndromes
    DIAGNOSIS

. The

    heart
    SYMPTOMS

 is always affected by

    myocardial fibrosis
    SYMPTOMS

 with

    early involvement of the right side
    SYMPTOMS

. Traditionally,

    ECG
    PARACLINICAL

,

    echocardiography
    PARACLINICAL

 and

    stress testing
    PARACLINICAL

 have been used to evaluate these patients.

    Cardiac MRI
    PARACLINICAL

, offering

    superior assessment of the right side
    PARACLINICAL

 and visualization of the

    myocardial fibrosis
    SYMPTOMS

 could become the preferred imaging modality for evaluating patients with

    BMD
    DIAGNOSIS

.

Becker's muscular dystrophy (BMD)
muscular dystrophy syndromes
BMD

heart
myocardial fibrosis
early involvement of the right side
myocardial fibrosis


Pericardial effusion with cardiac tamponade as a cardiac manifestation of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common hereditary neuromuscular disease in children. It is an X-linked hereditary dystrophinopathy due to the absence of dystrophin. Its onset is often in early childhood and presents with proximal distribution of weakness and a progressive course. Cardiac involvement in DMD is common, and its onset is usually after the age of 10 years. The most common cardiac manifestations are a dilated cardiomyopathy and cardiac arrhythmia. However, pericardial effusion with cardiac tamponade is a very rare cardiac complication of DMD. We report a boy with DMD who initially presented with progressive dyspnea and an enlarged cardiac silhouette on chest radiography who subsequently developed a large pericardial effusion with cardiac tamponade. Early recognition of pericardial effusion with cardiac tamponade is important for institution appropriate therapy.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is the most common

    hereditary neuromuscular disease
    DIAGNOSIS

 in

    children
    AGE

. It is an

    X-linked hereditary
    GENETICS

    dystrophinopathy
    DIAGNOSIS

 due to the

    absence of dystrophin
    BIOCHEMICAL

. Its onset is often

    in early childhood
    AGE

 and presents with

    proximal distribution of weakness
    SYMPTOMS

 and a

    progressive course
    SYMPTOMS

.

    Cardiac involvement
    SYMPTOMS

 in

    DMD
    DIAGNOSIS

 is common, and its onset is usually

    after the age of 10 years
    AGE

. The most common

    cardiac manifestations
    SYMPTOMS

 are a

    dilated cardiomyopathy
    SYMPTOMS

 and

    cardiac arrhythmia
    SYMPTOMS

. However,

    pericardial effusion with cardiac tamponade
    SYMPTOMS

 is a very rare

    cardiac complication
    SYMPTOMS

 of

    DMD
    DIAGNOSIS

. We report a

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 who initially presented with

    progressive dyspnea
    SYMPTOMS

 and an

    enlarged cardiac silhouette
    SYMPTOMS

 on

    chest radiography
    PARACLINICAL

 who subsequently developed a

    large pericardial effusion with cardiac tamponade
    SYMPTOMS

. Early recognition of

    pericardial effusion with cardiac tamponade
    SYMPTOMS

 is important for institution appropriate therapy.

Duchenne muscular dystrophy (DMD)
hereditary neuromuscular disease
dystrophinopathy
DMD
DMD
DMD


Scoliosis repair in a teenager with Duchenne's muscular dystrophy: who calls the shots?

In this exchange, a clinician (the first author) presents a case scenario for comment by an ethicist (the second author). The case concerns a 15-year-old boy with Duchenne's muscular dystrophy requested palliative surgical correction of a 60 degree thoraco-lumbar scoliosis. The surgical team were initially reluctant to offer surgery given their assessment of the perioperative and postoperative risks (anesthetic review suggested an 80% chance of surviving the surgery and 50% likelihood of returning home), but the operation proceeded. The case raises issues of the rights of patients to insist on nonfutile but high risk surgery, risk perception, resource allocation, autonomy, and the integrity of clinicians.

In this exchange, a clinician (the first author) presents a case scenario for comment by an

    ethicist
    PARACLINICAL

 (the second author). The case concerns a

    15-year-old
    AGE

    boy
    GENDER

 with

    Duchenne's muscular dystrophy
    DIAGNOSIS

 requested

    palliative surgical correction of a 60 degree thoraco-lumbar scoliosis
    MEDICATION

. The

    surgical team were initially reluctant to offer surgery
    NEG_FINDINGS

 given their assessment of the perioperative and postoperative risks (anesthetic review suggested an 80% chance of

    surviving the surgery
    MEDICATION

 and 50% likelihood of returning home), but the

    operation
    MEDICATION

 proceeded. The case raises issues of the rights of patients to insist on

    nonfutile but high risk surgery
    NEG_FINDINGS

, risk perception, resource allocation, autonomy, and the integrity of clinicians.


Insertion of the IL1RAPL1 gene into the duplication junction of the dystrophin gene.

Duplications of one or more exons of the dystrophin gene are the second most common mutation in dystrophinopathies. Even though duplications are suggested to occur with greater complexity than thought earlier, they have been considered an intragenic event. Here, we report the insertion of a part of the IL1RAPL1 (interleukin-1 receptor accessory protein-like 1) gene into the duplication junction site. When the actual exon junction was examined in 15 duplication mutations in the dystrophin gene by analyzing dystrophin mRNA, one patient was found to have an unknown 621 bp insertion at the junction of duplication of exons from 56 to 62. Unexpectedly, the inserted sequence was found completely identical to sequences of exons 3-5 of the IL1RAPL1 gene that is nearly 100 kb distal from the dystrophin gene. Accordingly, the insertion of IL1RAPL1 exons 3-5 between dystrophin exons 62 and 56 was confirmed at the genomic sequence level. One junction between the IL1RAPL1 intron 5 and dystrophin intron 55 was localized within an Alu sequence. These results showed that a fragment of the IL1RAPL1 gene was inserted into the duplication junction of the dystrophin gene in the same direction as the dystrophin gene. This suggests the novel possibility of co-occurrence of complex genomic rearrangements in dystrophinopathy.

    Duplications of one or more exons of the dystrophin gene
    GENETICS

 are the second most common mutation in

    dystrophinopathies
    DIAGNOSIS

. Even though

    duplications
    GENETICS

 are suggested to occur with greater complexity than thought earlier, they have been considered an intragenic event. Here, we report the

    insertion of a part of the IL1RAPL1 (interleukin-1 receptor accessory protein-like 1) gene into the duplication junction site
    GENETICS

. When

    the actual exon junction was examined in
    PARACLINICAL

 15

    duplication mutations in the dystrophin gene
    GENETICS

 by

    analyzing dystrophin mRNA
    PARACLINICAL

, one patient was found to have an

    unknown 621 bp insertion at the junction of duplication of exons from 56 to 62
    GENETICS

. Unexpectedly,

    the inserted sequence was found completely identical to sequences of exons 3-5 of the IL1RAPL1 gene that is nearly 100 kb distal from the dystrophin gene
    GENETICS

. Accordingly, the

    insertion of IL1RAPL1 exons 3-5 between dystrophin exons 62 and 56
    GENETICS

 was confirmed at the

    genomic sequence level
    PARACLINICAL

.

    One junction between the IL1RAPL1 intron 5 and dystrophin intron 55 was localized within an Alu sequence
    GENETICS

. These results showed that a

    fragment of the IL1RAPL1 gene was inserted into the duplication junction of the dystrophin gene in the same direction as the dystrophin gene
    GENETICS

. This suggests the novel possibility of

    co-occurrence of complex genomic rearrangements
    GENETICS

 in

    dystrophinopathy
    DIAGNOSIS

.


Somatic mosaicism for Duchenne dystrophy: evidence for genetic normalization mitigating muscle symptoms.

We describe a young adult male presenting with cardiac failure necessitating cardiac transplantation 7 months after presentation. Skeletal muscle biopsy showed mosaic immunostaining for dystrophin. DNA studies showed somatic mosaicism for a nonsense mutation in the dystrophin gene (Arg2905X). The frequency of normal versus mutant genes were determined in blood/DNA (50:50), muscle/DNA (80:20) and muscle/mRNA (90:10). These data are consistent with genetic normalization processes that may biochemically rescue skeletal muscle in male somatic mosaic patients mitigating muscle symptoms (gradual loss of dystrophin-negative skeletal muscle tissue replaced by dystrophin-positive stem cells). To our knowledge, this is only the second reported case of a clinically ascertained patient showing somatic mosaicism for Duchenne muscular dystrophy (DMD). We hypothesize that many somatic mosaic males for DMD exist, yet they are not detected clinically due to genetic normalization. Somatic mosaicism for DMD should be considered in acute heart failure with dilated cardiomyopathy, as genetic normalization in heart is unlikely to occur.

We describe a

    young adult
    AGE

    male
    GENDER

 presenting with

    cardiac failure
    SYMPTOMS

 necessitating

    cardiac transplantation
    MEDICATION

 7 months after presentation.

    Skeletal muscle biopsy
    PARACLINICAL

 showed

    mosaic immunostaining for dystrophin
    MICROSCOPIC

.

    DNA studies
    PARACLINICAL

 showed

    somatic mosaicism for a nonsense mutation in the dystrophin gene (Arg2905X)
    GENETICS

. The

    frequency of normal versus mutant genes were determined in blood/DNA
    GENETICS

 (50:50), muscle/DNA (80:20) and muscle/mRNA (90:10). These data are consistent with genetic normalization processes that may biochemically

    rescue skeletal muscle
    SYMPTOMS

 in

    male
    GENDER

    somatic mosaic
    GENETICS

 patients

    mitigating muscle symptoms
    SYMPTOMS

 (

    gradual loss of dystrophin-negative skeletal muscle tissue replaced by dystrophin-positive stem cells)
    MICROSCOPIC

. To our knowledge, this is only the second reported case of a clinically ascertained patient showing

    somatic mosaicism for Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. We hypothesize that many

    somatic mosaic males
    GENETICS

 for

    DMD
    DIAGNOSIS

 exist, yet they are not detected clinically due to

    genetic normalization
    NEG_FINDINGS

.

    Somatic mosaicism for DMD
    DIAGNOSIS

 should be considered in

    acute heart failure
    SYMPTOMS

 with

    dilated cardiomyopathy
    SYMPTOMS

, as

    genetic normalization in heart is unlikely to occur
    NEG_FINDINGS

.

cardiac failure
rescue skeletal muscle
mitigating muscle symptoms
acute heart failure
dilated cardiomyopathy


Molecular characterization of co-occurring Duchenne muscular dystrophy and X-linked oculo-facio-cardio-dental syndrome in a girl.

Duchenne muscular dystrophy is an X-linked condition at the severe end of the spectrum of dystrophinopathies. Females with dystrophin mutations are at risk for cardiomyopathy, but are usually asymptomatic during childhood. However, some girls can exhibit features of Duchenne muscular dystrophy because of skewed X-inactivation, aneuploidy, or chromosomal rearrangement. Oculo-facio-cardio-dental syndrome is a rare X-linked disorder, lethal in males, that comprises microphthalmia, congenital cataracts, congenital heart defect, canine radiculomegaly, and digital anomalies. We report on a 7-year-old girl who was referred for muscular hypotonia, with clinical features of Duchenne muscular dystrophy, including elevated serum creatine phosphokinase, pseudohypertrophy of calf muscles, and muscle weakness, which became evident at 3 years of age. In addition, she had multiple congenital anomalies including atrial septal defect, cataracts, dental and digital anomalies, a constellation that suggested the diagnosis of oculo-facio-cardio-dental syndrome, a condition caused by mutations in BCOR. Immunohistochemistry and Western blot analysis of muscle, and mutation analysis of DMD showed a maternally inherited deletion of exons 30-43, confirming the diagnosis of Duchenne muscular dystrophy. Studies of lymphocytes showed essentially complete skewing of X-inactivation. Mutation analysis of BCOR revealed a de novo frameshift mutation (c.1005delC). Thus, we report for the first time on an individual with the co-occurrence of Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is an

    X-linked
    GENETICS

 condition at the severe end of the spectrum of

    dystrophinopathies
    DIAGNOSIS

.

    Females
    GENDER

 with

    dystrophin mutations
    GENETICS

 are at risk for

    cardiomyopathy
    DIAGNOSIS

, but are usually

    asymptomatic
    NEG_FINDINGS

 during

    childhood
    AGE

. However, some

    girls
    GENDER

 can exhibit features of

    Duchenne muscular dystrophy
    DIAGNOSIS

 because of

    skewed X-inactivation
    GENETICS

,

    aneuploidy
    GENETICS

, or

    chromosomal rearrangement
    GENETICS

.

    Oculo-facio-cardio-dental syndrome
    DIAGNOSIS

 is a

    rare X-linked disorder
    GENETICS

, lethal in

    males
    GENDER

, that comprises

    microphthalmia
    SYMPTOMS

,

    congenital cataracts
    SYMPTOMS

,

    congenital heart defect
    SYMPTOMS

,

    canine radiculomegaly
    SYMPTOMS

, and

    digital anomalies
    SYMPTOMS

. We report on a

    7-year-old
    AGE

    girl
    GENDER

 who was referred for

    muscular hypotonia
    SYMPTOMS

, with

    clinical features of Duchenne muscular dystrophy
    SYMPTOMS

, including

    elevated serum creatine phosphokinase
    BIOCHEMICAL

,

    pseudohypertrophy of calf muscles
    SYMPTOMS

, and

    muscle weakness
    SYMPTOMS

, which became evident

    at 3 years of age
    AGE

. In addition,

    she
    GENDER

 had

    multiple congenital anomalies
    SYMPTOMS

 including

    atrial septal defect
    SYMPTOMS

,

    cataracts
    SYMPTOMS

,

    dental and digital anomalies
    SYMPTOMS

, a constellation that suggested the diagnosis of

    oculo-facio-cardio-dental syndrome
    DIAGNOSIS

, a condition caused by

    mutations in BCOR
    GENETICS

.

    Immunohistochemistry and Western blot analysis of muscle
    PARACLINICAL

, and

    mutation analysis of DMD
    PARACLINICAL

 showed a

    maternally inherited deletion of exons 30-43
    GENETICS

, confirming the diagnosis of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    Studies of lymphocytes
    PARACLINICAL

 showed

    essentially complete skewing of X-inactivation
    GENETICS

.

    Mutation analysis of BCOR
    PARACLINICAL

 revealed a

    de novo frameshift mutation (c.1005delC)
    GENETICS

. Thus, we report for the first time on an individual with the

    co-occurrence of Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome
    DIAGNOSIS

.


Helmet ventilation for acute respiratory failure and nasal skin breakdown in neuromuscular disorders.

Noninvasive ventilation (NIV) has been widely used to decrease the complications associated with tracheal intubation in mechanically ventilated patients with neuromuscular diseases in acute respiratory failure. However, nasal ulcerations might occur when masks are used as an interface. Helmet ventilation is a possible option in this case. We describe two patients with acute respiratory failure due to Duchenne muscular dystrophy who developed nasal bridge skin necrosis during NIV. Helmet pressure support ventilation caused significant patient-ventilator asynchrony, leading to NIV intolerance. Thus, biphasic positive airway pressure delivered by helmet was applied, which improved gas exchange and patient-ventilator interaction, allowing successful NIV.

    Noninvasive ventilation (NIV)
    MEDICATION

 has been widely used to

    decrease the complications associated with tracheal intubation
    SYMPTOMS

 in

    mechanically ventilated
    MEDICATION

 patients with

    neuromuscular diseases
    DIAGNOSIS

 in

    acute respiratory failure
    SYMPTOMS

. However,

    nasal ulcerations
    SYMPTOMS

 might occur when masks are used as an interface.

    Helmet ventilation
    MEDICATION

 is a possible option in this case. We describe two patients with

    acute respiratory failure
    SYMPTOMS

 due to

    Duchenne muscular dystrophy
    DIAGNOSIS

 who developed

    nasal bridge skin necrosis
    SYMPTOMS

 during

    NIV
    MEDICATION

.

    Helmet pressure support ventilation
    MEDICATION

 caused

    significant patient-ventilator asynchrony
    SYMPTOMS

, leading to

    NIV intolerance
    NEG_FINDINGS

. Thus,

    biphasic positive airway pressure delivered by helmet
    MEDICATION

 was applied, which

    improved gas exchange and patient-ventilator interaction
    SYMPTOMS

, allowing

    successful NIV
    MEDICATION

.

neuromuscular diseases
Duchenne muscular dystrophy


Is there a duty to share genetic information?

A number of prominent bioethicists, such as Parker, Lucassen and Knoppers, have called for the adoption of a system in which by default genetic information is shared among family members. This paper suggests that a main reason given in support of this call to share genetic information among family members is the idea that genetic information is essentially familial in nature. On examining this "familial nature of genetics" argument, the paper shows that most genetic information is only shared in a weaker way among family members and does not necessarily lead to the actual manifestation of particular diseases. The upshot is that the idea that genetic information is familial in nature does not provide sufficient ground for moving towards a system in which by default genetic information is shared among family members.

A number of prominent bioethicists, such as Parker, Lucassen and Knoppers, have called for the adoption of a system in which by default genetic information is shared among family members. This paper suggests that a main reason given in support of this call to share genetic information among family members is the idea that

    genetic information is essentially familial in nature
    GENETICS

. On examining this "

    familial nature of genetics
    GENETICS

" argument, the paper shows that most genetic information is only shared in a weaker way among family members and does not necessarily lead to the actual manifestation of particular diseases. The upshot is that the idea that

    genetic information is familial in nature
    GENETICS

 does not provide sufficient ground for moving towards a system in which by default genetic information is shared among family members.