[Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia.

Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L-1 (normal 174IU.L-1). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy.

On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia.

    Duchenne/Becker muscular dystrophy
    DIAGNOSIS

 affects

    skeletal muscles
    SYMPTOMS

 and leads to

    progressive muscle weakness
    SYMPTOMS

 and risk of

    atypical anesthetic reactions following exposure to succinylcholine or halogenated agents
    SYMPTOMS

. The aim of this report is to describe the investigation and diagnosis of a patient with

    Becker muscular dystrophy
    DIAGNOSIS

 and review the care required in

    anesthesia
    MEDICATION

.

    Male
    GENDER

 patient,

    14 years old
    AGE

, referred for

    hyperCKemia
    BIOCHEMICAL

 (

    chronic increase of serum creatine kinase levels - CK)
    BIOCHEMICAL

, with

    CK values of 7,779-29,040IU.L-1 (normal 174IU.L-1)
    BIOCHEMICAL

.

    He
    GENDER

 presented with a

    discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months
    SYMPTOMS

).

    He
    GENDER

 had a

    history of liver transplantation
    MEDICATION

. In the

    neurological examination
    PARACLINICAL

, the patient showed

    difficulty in walking on one's heels
    SYMPTOMS

,

    myopathic sign (hands supported on the thighs to stand)
    SYMPTOMS

,

    high arched palate
    SYMPTOMS

,

    calf hypertrophy
    SYMPTOMS

,

    winged scapulae
    SYMPTOMS

,

    global muscle hypotonia
    SYMPTOMS

 and

    arreflexia
    SYMPTOMS

.

    Spirometry
    PARACLINICAL

 showed

    mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted)
    SYMPTOMS

.

    The in vitro muscle contracture test in response to halothane and caffeine was normal
    NEG_FINDINGS

.

    Muscular dystrophy analysis by Western blot
    PARACLINICAL

 showed

    reduced dystrophin (20% of normal) for both antibodies (C and N-terminal)
    BIOCHEMICAL

, allowing the diagnosis of

    Becker muscular dystrophy
    DIAGNOSIS

.

On preanesthetic assessment, the history of

    delayed motor development
    SYMPTOMS

, as well as

    clinical and/or laboratory signs of myopathy
    SYMPTOMS

, should encourage

    neurological evaluation
    PARACLINICAL

, aiming at diagnosing

    subclinical myopathies
    DIAGNOSIS

 and planning the necessary care to prevent

    anesthetic complications
    SYMPTOMS

.

    Duchenne/Becker muscular dystrophy
    DIAGNOSIS

, although it does not increase susceptibility to

    MH
    DIAGNOSIS

, may lead to

    atypical fatal reactions in anesthesia
    SYMPTOMS

.

Duchenne/Becker muscular dystrophy
Becker muscular dystrophy
Becker muscular dystrophy
subclinical myopathies
Duchenne/Becker muscular dystrophy
MH

anesthesia
history of liver transplantation


An Unusual Triad in Pediatric Neurology: A Case Report on Cerebral Palsy, Epilepsy, and Duchenne Muscular Dystrophy.

We present a case of an unusual triad in pediatric neurology: a currently 12-year-old boy with cerebral palsy and epilepsy who was later also diagnosed with Duchenne muscular dystrophy. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different neurological disorders may overshadow each other. In addition, it demonstrates that every child with cerebral palsy and either an atypical clinical course or with inexplicable laboratory values-as well as every infant boy born to a theoretical Duchenne muscular dystrophy carrier-should be subjected to additional investigations.

We present a case of an unusual triad in

    pediatric neurology
    PARACLINICAL

: a

    currently 12-year-old
    AGE

    boy
    GENDER

 with

    cerebral palsy
    SYMPTOMS

 and

    epilepsy
    SYMPTOMS

 who was later also diagnosed with

    Duchenne muscular dystrophy
    DIAGNOSIS

. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different

    neurological disorders
    DIAGNOSIS

 may overshadow each other. In addition, it demonstrates that every

    child
    AGE

 with

    cerebral palsy
    SYMPTOMS

 and either an

    atypical clinical course
    SYMPTOMS

 or with

    inexplicable laboratory values
    SYMPTOMS

-as well as every

    infant
    AGE

    boy
    GENDER

 born to a theoretical

    Duchenne muscular dystrophy carrier
    DIAGNOSIS

-should be subjected to additional investigations.

cerebral palsy
epilepsy
cerebral palsy
atypical clinical course
inexplicable laboratory values

Duchenne muscular dystrophy
neurological disorders
Duchenne muscular dystrophy carrier


Two Cases of Duchenne Muscular Dystrophy That Showed Different Reactions to Nerve Stimulation During Peripheral Nerve Block: A Case Report.

In recent years, the technique of combined ultrasound and electrical stimulation-guided nerve block has been recommended. We present 2 patients with Duchenne muscular dystrophy who exhibited different muscle responses to nerve stimulation during the performance of peripheral nerve blocks for surgeries. Whereas a 2-year-old boy without severe disability showed the expected muscle contraction to electrical nerve stimulation, a 14-year-old boy with severe disability showed no muscle response. Our experience suggests that muscle responses to electrical nerve stimulation will vary with the stage of Duchenne muscular dystrophy.

In recent years, the technique of

    combined ultrasound and electrical stimulation-guided nerve block
    PARACLINICAL

 has been recommended. We present 2 patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who exhibited different muscle responses to nerve stimulation during the performance of

    peripheral nerve blocks
    MEDICATION

 for

    surgeries
    MEDICATION

. Whereas a

    2-year-old
    AGE

    boy
    GENDER

    without severe disability
    NEG_FINDINGS

 showed the

    expected muscle contraction to electrical nerve stimulation
    SYMPTOMS

, a

    14-year-old
    AGE

    boy
    GENDER

 with

    severe disability
    SYMPTOMS

 showed

    no muscle response
    NEG_FINDINGS

. Our experience suggests that muscle responses to electrical nerve stimulation will vary with the stage of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy

without severe disability
no muscle response


Duchenne muscular dystrophy in a female with compound heterozygous contiguous exon deletions.

Females with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) mutations rarely exhibit clinical symptoms from childhood, although potential mechanisms for symptoms associated with DMD and BMD in females have been reported. We report the case of a female DMD patient with a clinical course indistinguishable from that of a male DMD patient, and who possessed compound heterozygous contiguous exon deletions in the dystrophin gene. She exhibited Gowers' sign, calf muscle hypertrophy, and a high serum creatine kinase level at 2 years. Her muscle pathology showed most of the fibers were negative for dystrophin immunohistochemical staining. She lost ambulation at 11 years. Multiplex ligation-dependent probe amplification analysis of this gene detected one copy of exons 48-53; she was found to be a BMD carrier with an in-frame deletion. Messenger RNA from her muscle demonstrated out-of-frame deletions of exons 48-50 and 51-53 occurring on separate alleles. Genomic DNA from her lymphocytes demonstrated the accurate deletion region on each allele. To our knowledge, this is the first report on a female patient possessing compound heterozygous contiguous exon deletions in the dystrophin gene, leading to DMD.

    Females
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 and

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 mutations rarely exhibit

    clinical symptoms
    SYMPTOMS

 from

    childhood
    AGE

, although potential mechanisms for symptoms associated with

    DMD
    DIAGNOSIS

 and

    BMD
    DIAGNOSIS

 in

    females
    GENDER

 have been reported. We report the case of a

    female
    GENDER

    DMD
    DIAGNOSIS

 patient with a

    clinical course indistinguishable from that of
    SYMPTOMS

 a

    male
    GENDER

    DMD
    DIAGNOSIS

 patient, and who possessed

    compound heterozygous contiguous exon deletions in the dystrophin gene
    GENETICS

.

    She
    GENDER

 exhibited

    Gowers' sign
    SYMPTOMS

,

    calf muscle hypertrophy
    SYMPTOMS

, and a

    high serum creatine kinase level at 2 years
    BIOCHEMICAL

.

    Her
    GENDER

    muscle pathology
    PARACLINICAL

 showed

    most of the fibers were negative for dystrophin immunohistochemical staining
    MICROSCOPIC

.

    She
    GENDER

    lost ambulation
    SYMPTOMS

    at 11 years
    AGE

.

    Multiplex ligation-dependent probe amplification analysis of this gene detected one copy of exons 48-53
    PARACLINICAL

;

    she
    GENDER

    was found to be a BMD carrier with an in-frame deletion
    FAMILY

.

    Messenger RNA from her muscle
    PARACLINICAL

 demonstrated

    out-of-frame deletions of exons 48-50 and 51-53 occurring on separate alleles
    GENETICS

.

    Genomic DNA from her lymphocytes
    PARACLINICAL

    demonstrated the accurate deletion region on each allele
    GENETICS

. To our knowledge, this is the first report on a

    female
    GENDER

 patient possessing

    compound heterozygous contiguous exon deletions in the dystrophin gene
    GENETICS

, leading to

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
Becker muscular dystrophy (BMD)
DMD
BMD
DMD
DMD
DMD


[Duchenne Muscle Dystrophy Caused Bronchial Obstruction].

Duchenne muscle dystrophy (DMD), X-linked recessive genetic disorder, causes a variety of complications including scoliosis. We report a case of bronchial obstruction and hemorrhage caused by scoliosis with DMD. A man in his forties having been hospitalized due to DMD since the age of 6, produced bloody sputum. A chest X-ray showed atelectasis in his right lower lung. A computed tomography and bronchoscopy indicated that scoliosis and thoracic deformity due to muscle dystrophy caused compression of a right main bronchus by the vertebra, leading to bronchial obstruction and bleeding. We decided to follow closely without therapy because the bleeding had stopped as of the bronchoscopy. A high-risk surgery or bronchial stenting may be needed if he presents with severe bleeding or infection.

    Duchenne muscle dystrophy (DMD)
    DIAGNOSIS

,

    X-linked recessive genetic disorder
    GENETICS

, causes a variety of complications including

    scoliosis
    SYMPTOMS

. We report a case of

    bronchial obstruction
    SYMPTOMS

 and

    hemorrhage
    SYMPTOMS

 caused by

    scoliosis
    DIAGNOSIS

 with

    DMD
    DIAGNOSIS

. A

    man
    GENDER

    in his forties
    AGE

 having been hospitalized due to

    DMD
    DIAGNOSIS

    since the age of 6
    AGE

, produced

    bloody sputum
    SYMPTOMS

. A

    chest X-ray
    PARACLINICAL

 showed

    atelectasis in his right lower lung
    SYMPTOMS

. A

    computed tomography
    PARACLINICAL

 and

    bronchoscopy
    PARACLINICAL

 indicated that

    scoliosis and thoracic deformity
    SYMPTOMS

 due to

    muscle dystrophy
    SYMPTOMS

 caused

    compression of a right main bronchus by the vertebra
    SYMPTOMS

, leading to

    bronchial obstruction
    SYMPTOMS

 and

    bleeding
    SYMPTOMS

. We decided to follow closely

    without therapy
    NEG_FINDINGS

 because

    the bleeding had stopped
    SYMPTOMS

 as of the

    bronchoscopy
    PARACLINICAL

. A

    high-risk surgery
    MEDICATION

 or

    bronchial stenting
    MEDICATION

 may be needed if he presents with

    severe bleeding
    SYMPTOMS

 or

    infection
    SYMPTOMS

.

Duchenne muscle dystrophy (DMD)
scoliosis
DMD
DMD


Hypokalemia-induced cardiac arrest in a Duchenne muscular dystrophy patient.

Duchenne muscular dystrophy (DMD) is a progressive myopathic disorder, inherited as X-linked recessive traits, in which muscle weakness is the primary symptom. Correlation between DMD and hypokalemia is reported in only three case reports. Recent investigations have focused on the nutritional management of patients with DMD. However, there are no data regarding recommendations on potassium intake. Description of case: We report the case of a 15-year-old male patient with DMD, who developed sudden cardiac arrest following severe hypokalemia (K: 1.3 mEq/L) during a lower respiratory tract infection. Hypokalemia was gradually corrected with intravenous potassium chloride. The patient, after a prolonged hospitalization due to hypoxic encephalopathy, was discharged from the Intensive Care Unit (ICU) on mechanical ventilation.

Severe hypokalemia is a rare complication of DMD, with potentially lethal consequences. Therefore, in patients with DMD, potassium levels should be closely monitored and adjusted with appropriate diet or potassium supplements as needed. Hippokratia 2016, 20(2): 163-165.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    progressive myopathic disorder
    DIAGNOSIS

,

    inherited as X-linked recessive traits
    GENETICS

, in which

    muscle weakness
    SYMPTOMS

 is the primary symptom. Correlation between

    DMD
    DIAGNOSIS

 and

    hypokalemia
    BIOCHEMICAL

 is reported in only three case reports. Recent investigations have focused on the

    nutritional management
    MEDICATION

 of patients with

    DMD
    DIAGNOSIS

. However, there are no data regarding recommendations on

    potassium intake
    MEDICATION

. Description of case: We report the case of a

    15-year-old
    AGE

    male
    GENDER

 patient with

    DMD
    DIAGNOSIS

, who developed

    sudden cardiac arrest
    SYMPTOMS

 following

    severe hypokalemia (K: 1.3 mEq/L)
    BIOCHEMICAL

 during a

    lower respiratory tract infection
    SYMPTOMS

.

    Hypokalemia
    BIOCHEMICAL

 was gradually corrected with

    intravenous potassium chloride
    MEDICATION

. The patient, after a

    prolonged hospitalization
    MEDICATION

 due to

    hypoxic encephalopathy
    SYMPTOMS

, was

    discharged from the Intensive Care Unit (ICU) on mechanical ventilation
    MEDICATION

.

    Severe hypokalemia
    BIOCHEMICAL

 is a rare complication of

    DMD
    DIAGNOSIS

, with

    potentially lethal consequences
    SYMPTOMS

. Therefore, in patients with

    DMD
    DIAGNOSIS

,

    potassium levels
    BIOCHEMICAL

 should be closely monitored and adjusted with appropriate diet or

    potassium supplements
    MEDICATION

 as needed. Hippokratia 2016, 20(2): 163-165.

Duchenne muscular dystrophy (DMD)
progressive myopathic disorder
DMD
DMD
DMD
DMD
DMD

muscle weakness
sudden cardiac arrest
lower respiratory tract infection
hypoxic encephalopathy
potentially lethal consequences

hypokalemia
severe hypokalemia (K: 1.3 mEq/L)
Hypokalemia
Severe hypokalemia
potassium levels


Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy: A case Report.

Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial.

An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward.

A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

Anesthetic management of patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is complicated because these patients are more sensitive to

    nondepolarizing neuromuscular blocking agents (NMBAs)
    NEG_FINDINGS

 and are vulnerable to

    postoperative complications
    SYMPTOMS

, such as

    postoperative residual curarization
    SYMPTOMS

 and

    respiratory failure
    SYMPTOMS

.

    Sugammadex
    MEDICATION

 is a new

    reversal agent for aminosteroidal NMBAs
    MEDICATION

, but its safety in

    children
    AGE

 is controversial.

An

    11-year-old
    AGE

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 underwent

    general anesthesia for a percutaneous nephrolithotomy
    MEDICATION

. We used

    rocuronium bromide and sugammadex
    MEDICATION

 to

    reverse the deep neuromuscular block
    MEDICATION

.

    Reversal of neuromuscular block
    MEDICATION

 was done 15 minutes after

    administration of 2 mg/kg of sugammadex
    MEDICATION

. The patient's recovery from anesthesia was uneventful, and

    he
    GENDER

 was

    discharged to the postoperative recovery ward
    MEDICATION

.

A

    delayed recovery was achieved
    SYMPTOMS

, but

    no adverse events
    NEG_FINDINGS

 were observed, such as

    recurarization or hypersensitivity to sugammadex
    NEG_FINDINGS

. We report

    safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block
    MEDICATION

 in a

    child
    AGE

 with

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
DMD

postoperative complications
postoperative residual curarization
respiratory failure
delayed recovery was achieved


Evaluation of Serial Casting for Boys with Duchenne Muscular Dystrophy: A Case Report.

To report the effects of below-knee serial casting in two boys with Duchenne muscular dystrophy who presented with well-preserved strength and calf shortening.

Bilateral below-knee serial casts were applied over two weeks with follow-up of daily stretching and wearing of customized night splints. Outcome measures were performed at baseline, 1, 3, 6, and 12 months post-casting. These included measures of calf length, leg strength, motor function, endurance, and spatio-temporal gait parameters.

Both boys completed serial casting with gains in muscle length. No adverse effects on strength or motor function were observed over a 12-month follow-up period.

To report the effects of

    below-knee serial casting
    MEDICATION

 in two

    boys
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who presented with

    well-preserved strength
    SYMPTOMS

 and

    calf shortening
    SYMPTOMS

.

    Bilateral below-knee serial casts were applied over two weeks
    MEDICATION

 with

    follow-up of daily stretching and wearing of customized night splints
    MEDICATION

. Outcome measures were performed at baseline, 1, 3, 6, and 12 months post

    -casting
    MEDICATION

. These included

    measures of calf length
    PARACLINICAL

,

    leg strength, motor function, endurance
    SYMPTOMS

, and

    spatio-temporal gait parameters
    SYMPTOMS

.

Both

    boys
    GENDER

 completed

    serial casting
    MEDICATION

 with

    gains in muscle length
    SYMPTOMS

.

    No adverse effects on strength or motor function were observed over a 12-month follow-up period
    NEG_FINDINGS

.

well-preserved strength
calf shortening
leg strength, motor function, endurance
spatio-temporal gait parameters
gains in muscle length


Co-incidence of Turner syndrome and Duchenne muscular dystrophy - an important problem for the clinician.

Turner syndrome is a relatively common chromosomal disorder which affects about one in 2000 live born females. Duchenne muscular dystrophy is an X-linked recessive disorder affecting 1:3600 live born males. Considering the above, the coexistence of these two diseases may occur only anecdotally.

Here, we report a 4 ½ year-old female with classical 45,X Turner syndrome who also had Duchenne muscular dystrophy caused by a point mutation in the dystrophin gene (c.9055delG). The patient showed the typical phenotype of Turner syndrome including distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples), aortic coarctation and feet lymphedema. Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy.

The coexistence of an X-linked recessive disorder should be considered in women affected by Turner syndrome presenting with additional atypical clinical features.

    Turner syndrome
    DIAGNOSIS

 is a relatively common

    chromosomal disorder
    DIAGNOSIS

 which affects about one in 2000 live born

    females
    GENDER

.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is an

    X-linked recessive disorder
    GENETICS

 affecting 1:3600 live born

    males
    GENDER

. Considering the above, the coexistence of these two diseases may occur only anecdotally.

Here, we report a

    4 ½ year-old
    AGE

    female
    GENDER

 with

    classical 45,X Turner syndrome
    GENETICS

 who also had

    Duchenne muscular dystrophy
    DIAGNOSIS

 caused by a

    point mutation in the dystrophin gene (c.9055delG)
    GENETICS

. The patient showed the typical phenotype of

    Turner syndrome
    DIAGNOSIS

 including

    distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples)
    SYMPTOMS

,

    aortic coarctation
    SYMPTOMS

 and

    feet lymphedema
    SYMPTOMS

. Besides,

    she
    GENDER

 presented with an

    unusually early beginning of muscular dystrophy symptoms
    SYMPTOMS

 with

    infantile-onset motor developmental delay
    SYMPTOMS

,

    intellectual disability
    SYMPTOMS

 and

    early calf muscular hypertrophy
    SYMPTOMS

.

The

    coexistence of an X-linked recessive disorder
    GENETICS

 should be considered in

    women
    GENDER

 affected by

    Turner syndrome
    DIAGNOSIS

 presenting with

    additional atypical clinical features
    SYMPTOMS

.

Turner syndrome
chromosomal disorder
Duchenne muscular dystrophy
Duchenne muscular dystrophy
Turner syndrome
Turner syndrome


Phenotypic contrasts of Duchenne Muscular Dystrophy in women: Two case reports.

We discussed two cases of symptomatic female carriers to Duchenne Muscular Dystrophy. The first case is a 20 year-old girl with classical phenotypic manifestation of the disease, similar to the condition in boys. The case 2 is a 62 year-old woman with progressive muscular weakness. The disease is much less common in woman than men so both cases described here are considered rare forms of the disease, with several clinical implications. In both cases, a progressive muscle weakness, impairment in walking and sleeping was observed, in addition to obstructive sleep apnea syndrome and alveolar hypoventilation, that required noninvasive ventilatory support.

We discussed two cases of symptomatic

    female
    GENDER

 carriers to

    Duchenne Muscular Dystrophy
    DIAGNOSIS

. The first case is a

    20 year-old
    AGE

    girl
    GENDER

 with

    classical phenotypic manifestation of the disease
    SYMPTOMS

, similar to the condition in

    boys
    GENDER

. The case 2 is a

    62 year-old
    AGE

    woman
    GENDER

 with

    progressive muscular weakness
    SYMPTOMS

. The disease is much less common in

    woman
    GENDER

 than

    men
    GENDER

 so both cases described here are considered rare forms of the disease, with several clinical implications. In both cases, a

    progressive muscle weakness
    SYMPTOMS

,

    impairment in walking and sleeping
    SYMPTOMS

 was observed, in addition to

    obstructive sleep apnea syndrome
    SYMPTOMS

 and

    alveolar hypoventilation
    SYMPTOMS

, that required

    noninvasive ventilatory support
    MEDICATION

.


Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients.

To evaluate mouthpiece ventilation (MPV) in patients with Duchenne muscular dystrophy (DMD) who are noncompliant with noninvasive ventilation (NIV).

We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV.

The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night.

The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces.

Avaliar a ventilação bucal (VB) em pacientes com distrofia muscular de Duchenne (DMD) não aderentes à ventilação não invasiva (VNI).

Foram avaliados quatro pacientes jovens com DMD que anteriormente recusaram-se a se submeter à VNI. Cada paciente foi reavaliado e encorajado a tentar VB.

Os quatro pacientes toleraram bem a VB e aderiram ao uso de VNI em casa. O uso de VB provou ser uma alternativa preferível e mais confortável que o uso de VNI com qualquer outro tipo de interface. Dois dos pacientes necessitaram de VNI noturna e eventualmente aceitaram utilizar uma máscara nasal durante a noite.

As vantagens da VB sobre outros tipos de VNI incluem menores problemas na fala, melhor aparência e menor impacto no paciente, eliminando o risco de lesões na pele, distensão gástrica, conjuntivite e claustrofobia. O uso da interface bucal sempre deve ser considerado em pacientes com DMD que necessitam iniciar VNI a fim de promover uma abordagem positiva e uma rápida aceitação da VNI. O uso diurno de VB faz com que os pacientes sintam-se seguros e mais propensos a utilizar VNI à noite. Além disso, a VB aumenta a adesão ao tratamento naqueles pacientes que se recusam a utilizar outros tipos de interfaces.

To evaluate

    mouthpiece ventilation (MPV)
    MEDICATION

 in patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 who are

    noncompliant with noninvasive ventilation (NIV)
    NEG_FINDINGS

.

We evaluated four

    young
    AGE

 patients with

    DMD
    DIAGNOSIS

 who had

    previously refused to undergo NIV
    NEG_FINDINGS

. Each patient was reassessed and encouraged to try

    MPV
    MEDICATION

.

The four patients tolerated

    MPV
    MEDICATION

 well and were

    compliant with NIV at home
    MEDICATION

.

    MPV
    MEDICATION

 proved to be preferable and more comfortable than

    NIV with any other type of interface
    MEDICATION

. Two of the patients required

    overnight NIV
    MEDICATION

 and eventually

    agreed to use a nasal mask during the night
    MEDICATION

.

The advantages of

    MPV
    MEDICATION

 over other

    types of NIV
    MEDICATION

 include

    fewer speech problems
    SYMPTOMS

, better appearance, and

    less impact on the patient
    SYMPTOMS

, eliminating the risk of

    skin breakdown
    SYMPTOMS

,

    gastric distension
    SYMPTOMS

,

    conjunctivitis
    SYMPTOMS

, and

    claustrophobia
    SYMPTOMS

. The

    use of a mouthpiece interface
    MEDICATION

 should be always considered in patients with

    DMD
    DIAGNOSIS

 who need to start

    NIV
    MEDICATION

, in order to promote a positive approach and a rapid acceptance of

    NIV
    MEDICATION

.

    Using MPV during the daytime
    MEDICATION

 makes patients feel safe and more likely to

    use NIV
    MEDICATION

 at night. In addition,

    MPV
    MEDICATION

 increases

    treatment compliance
    MEDICATION

 for those who

    refuse to use other types of interfaces
    NEG_FINDINGS

.

Avaliar a

    ventilação bucal (VB)
    MEDICATION

 em pacientes com

    distrofia muscular de Duchenne (DMD)
    DIAGNOSIS

 não aderentes à

    ventilação não invasiva (VNI)
    NEG_FINDINGS

.

Foram avaliados quatro pacientes jovens com DMD que anteriormente recusaram-se a se submeter à

    VNI
    DIAGNOSIS

. Cada paciente foi reavaliado e encorajado a

    tentar VB
    DIAGNOSIS

.

Os quatro pacientes toleraram bem a VB e aderiram ao uso de VNI em casa. O uso de VB provou ser uma alternativa preferível e mais confortável que o uso de VNI com qualquer outro tipo de interface. Dois dos pacientes necessitaram de VNI noturna e eventualmente aceitaram

    utilizar uma máscara nasal
    MEDICATION

 durante a noite.

As vantagens da VB sobre outros tipos de VNI incluem

    menores problemas na fala
    SYMPTOMS

,

    melhor aparência
    SYMPTOMS

 e menor impacto no paciente, eliminando o

    risco de lesões na pele
    SYMPTOMS

,

    distensão gástrica
    SYMPTOMS

,

    conjuntivite
    SYMPTOMS

 e

    claustrofobia
    SYMPTOMS

. O uso da interface bucal sempre deve ser considerado em pacientes com DMD que necessitam iniciar

    VNI
    MEDICATION

 a fim de promover uma abordagem positiva e uma rápida aceitação da VNI. O uso diurno de VB faz com que os pacientes sintam-se seguros e mais propensos a utilizar

    VNI
    MEDICATION

 à noite. Além disso, a

    VB
    MEDICATION

 aumenta a adesão ao tratamento naqueles pacientes que se recusam a

    utilizar outros tipos de interfaces
    MEDICATION

.

Duchenne muscular dystrophy (DMD)
DMD
DMD
distrofia muscular de Duchenne (DMD)
VNI
tentar VB

fewer speech problems
less impact on the patient
skin breakdown
gastric distension
conjunctivitis
claustrophobia
menores problemas na fala
melhor aparência
risco de lesões na pele
distensão gástrica
conjuntivite
claustrofobia


Cryptic splice activation but not exon skipping is observed in minigene assays of dystrophin c.9361+1G>A mutation identified by NGS.

Next-generation sequencing (NGS) discloses nucleotide changes in the genome. Mutations at splicing regulatory elements are expected to cause splicing errors, such as exon skipping, cryptic splice site activation, partial exon loss or intron retention. In dystrophinopathy patients, prediction of splicing outcomes is essential to determine the phenotype: either severe Duchenne or mild Becker muscular dystrophy, based on the reading frame rule. In a Vietnamese patient, NGS identified a c.9361+1G>A mutation in the dystrophin gene and an additional DNA variation of A>G at +117 bases in intron 64. To ascertain the consequences of these DNA changes on dystrophin splicing, minigene constructs were prepared inserting dystrophin exon 64 plus various lengths of intron 64. Exon 64 skipping was observed in the minigene construct with 160 nucleotide (nt) of intron 64 sequence with both c.9361+1A and +117G. In contrast, minigene constructs with larger flanking intronic domains resulted in cryptic splice site activation rather than exon skipping. Meanwhile, the cryptic splice site activation was induced even in +117G when intron 64 was elongated to 272 nt and longer. It was expected that cryptic splice site activation is an in vivo splicing outcome.

    Next-generation sequencing (NGS)
    GENETICS

 discloses

    nucleotide changes in the genome
    GENETICS

.

    Mutations at splicing regulatory elements
    GENETICS

 are expected to cause splicing errors, such as

    exon skipping
    GENETICS

,

    cryptic splice site activation
    SYMPTOMS

,

    partial exon loss
    SYMPTOMS

 or

    intron retention
    SYMPTOMS

. In

    dystrophinopathy
    DIAGNOSIS

 patients, prediction of splicing outcomes is essential to determine the phenotype: either

    severe Duchenne
    DIAGNOSIS

 or

    mild Becker muscular dystrophy
    DIAGNOSIS

, based on the reading frame rule. In a

    Vietnamese
    ETHNICITY

 patient,

    NGS
    PARACLINICAL

 identified a

    c.9361+1G>A mutation in the dystrophin gene
    GENETICS

 and an

    additional DNA variation of A>G at +117 bases in intron 64
    GENETICS

. To ascertain the consequences of these DNA changes on dystrophin splicing, minigene constructs were prepared inserting dystrophin exon 64 plus various lengths of intron 64.

    Exon 64 skipping
    GENETICS

 was observed in the minigene construct with 160 nucleotide (nt) of intron 64 sequence with both c.9361+1A and +117G. In contrast, minigene constructs with

    larger flanking intronic domains
    GENETICS

 resulted in

    cryptic splice site activation
    SYMPTOMS

    rather than exon skipping
    NEG_FINDINGS

. Meanwhile, the

    cryptic splice site activation was induced even in +117G when intron 64 was elongated to 272 nt and longer
    SYMPTOMS

. It was expected that

    cryptic splice site activation
    SYMPTOMS

 is an in vivo splicing outcome.

dystrophinopathy
severe Duchenne
mild Becker muscular dystrophy


New Survival Target for Duchenne Muscular Dystrophy.

We report a patient with a typical phenotype and clinical history of Duchenne muscular dystrophy who is currently 53 years old. Because of improvements in cardiopulmonary care, there has been a great improvement in survival and preservation of quality of life for many of these patients. Whereas it is no longer rare to find patients with Duchenne muscular dystrophy living into their fifth decade, this is the first report of a patient in his sixth decade of life. We believe that besides use of continuous noninvasive respiratory support, the fortuitous absence of dilated cardiomyopathy associated with the particular point mutation of his dystrophin gene has permitted prolonged survival.

We report a patient with a typical phenotype and clinical history of

    Duchenne muscular dystrophy
    DIAGNOSIS

 who is currently

    53 years old
    AGE

. Because of improvements in

    cardiopulmonary care
    MEDICATION

, there has been a great improvement in survival and

    preservation of quality of life
    SYMPTOMS

 for many of these patients. Whereas it is no longer rare to find patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

 living into

    their fifth decade
    AGE

, this is the first report of a patient in

    his
    GENDER

    sixth decade of life
    AGE

. We believe that besides use of

    continuous noninvasive respiratory support
    MEDICATION

, the fortuitous

    absence of dilated cardiomyopathy
    NEG_FINDINGS

 associated with the

    particular point mutation of his dystrophin gene
    GENETICS

 has permitted

    prolonged survival
    MEDICATION

.


Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia.

This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful.

A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine.

Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

    Inguinal hernia repairs
    MEDICATION

 are routinely performed as

    outpatient procedures
    MEDICATION

 in most patients, whereas a few require

    admission
    MEDICATION

 due to clinical or social peculiarities.

    Muscular dystrophies
    DIAGNOSIS

 are

    inherited disorders
    GENETICS

 characterized by

    progressive muscle wasting
    SYMPTOMS

 and

    weakness
    SYMPTOMS

. In case of

    surgery
    MEDICATION

 there is no definite recommendation for either

    general or regional anesthesia
    MEDICATION

.

This contribution regards a

    48 y. o.
    AGE

    male
    GENDER

 patient diagnosed with

    Becker Muscular Dystrophy
    DIAGNOSIS

 by

    muscle biopsy
    PARACLINICAL

 10 years earlier.

    He
    GENDER

 had a

    left-sided sizable inguinoscrotal hernia
    SYMPTOMS

 with

    repeat episodes of incarceration
    SYMPTOMS

. An

    elective mesh repair with suction drainage
    MEDICATION

 was accomplished under

    selective spinal anesthesia
    MEDICATION

. The post-operative course was uneventful.

A few

    inguinal hernia repairs
    MEDICATION

 require admission due to peculiarities such as

    extensive scrotal hernias
    SYMPTOMS

 requiring

    suction drainage
    MEDICATION

.

    Muscular dystrophies
    DIAGNOSIS

 are

    inherited disorders
    GENETICS

 with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of

    surgery
    MEDICATION

 there is no definite recommendation for either

    general or regional anesthesia
    MEDICATION

. This contribution regards the successful

    elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia
    MEDICATION

 in a

    48 y. o.
    AGE

    male
    GENDER

 patient affected by

    Becker muscular dystrophy
    DIAGNOSIS

 by

    selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine
    MEDICATION

.

    Effective mesh repair with suction drainage of large inguinal hernias
    MEDICATION

 under

    spinal anesthesia
    MEDICATION

 can be achieved in patients affected by

    muscular dystrophy
    DIAGNOSIS

.

Muscular dystrophies
Becker Muscular Dystrophy
Muscular dystrophies
Becker muscular dystrophy
muscular dystrophy


Mechanical insufflation-exsufflation for an individual with Duchenne muscular dystrophy and a lower respiratory infection.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy associated with progressive muscle weakness and wasting, loss of ambulation, respiratory insufficiency, weak cough, repeated respiratory infections, and ultimately death from respiratory failure in early adulthood. Mechanical insufflation-exsufflation (MI-E) devices, such as the CoughAssist®, are used in individuals with neuromuscular weakness to augment cough and help clear secretions; however, there is no consensus on the optimal treatment regimen. We present the challenging case of a patient with DMD admitted to a tertiary hospital with a severe lower respiratory infection, and discuss how MI-E was used by physiotherapists to assist secretion clearance and prevent further deterioration.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked recessive
    GENETICS

    myopathy
    DIAGNOSIS

 associated with

    progressive muscle weakness and wasting
    SYMPTOMS

,

    loss of ambulation
    SYMPTOMS

,

    respiratory insufficiency
    SYMPTOMS

,

    weak cough
    SYMPTOMS

,

    repeated respiratory infections
    SYMPTOMS

, and ultimately

    death
    SYMPTOMS

 from

    respiratory failure
    SYMPTOMS

 in

    early adulthood
    AGE

.

    Mechanical insufflation-exsufflation (MI-E) devices, such as the CoughAssist®
    MEDICATION

, are used in individuals with

    neuromuscular weakness
    DIAGNOSIS

 to

    augment cough and help clear secretions
    MEDICATION

; however, there is no consensus on the optimal treatment regimen. We present the challenging case of a patient with

    DMD
    DIAGNOSIS

 admitted to a tertiary hospital with a

    severe lower respiratory infection
    SYMPTOMS

, and discuss how

    MI-E
    MEDICATION

 was used by

    physiotherapists
    MEDICATION

 to

    assist secretion clearance
    MEDICATION

 and

    prevent further deterioration
    SYMPTOMS

.

Duchenne muscular dystrophy (DMD)
myopathy
neuromuscular weakness
DMD

progressive muscle weakness and wasting
loss of ambulation
respiratory insufficiency
weak cough
repeated respiratory infections
death
respiratory failure
severe lower respiratory infection
prevent further deterioration


A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare.

We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene.

The present case report helps to better understand the clinical and genetic features of BMD.

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

, a

    genetic disorder of X-linked recessive inheritance
    GENETICS

, typically presents with

    gradually progressive muscle weakness
    SYMPTOMS

. The condition is caused by

    mutations of Dystrophin gene located at Xp21.2
    GENETICS

.

    Epilepsy
    SYMPTOMS

 is an infrequent manifestation of

    BMD
    DIAGNOSIS

, while cases of

    BMD
    DIAGNOSIS

 with

    dysgnosia
    SYMPTOMS

 are extremely rare.

We describe a

    9-year-old
    AGE

    boy
    GENDER

 with

    BMD
    DIAGNOSIS

, who presented with

    epilepsy
    SYMPTOMS

 and

    dysgnosia
    SYMPTOMS

.

    Serum creatine kinase level was markedly elevated (3665 U/L)
    BIOCHEMICAL

.

    Wechsler intelligence tests
    PARACLINICAL

 showed a

    low intelligence quotient (IQ = 65)
    SYMPTOMS

.

    Electromyogram
    PARACLINICAL

 showed

    slight myogenic changes
    SYMPTOMS

 and

    skeletal muscle biopsy
    PARACLINICAL

 revealed

    muscular dystrophy
    DIAGNOSIS

.

    Immunohistochemical staining
    PARACLINICAL

 showed partial positivity of sarcolemma for dystrophin-N.

    Multiplex ligation-dependent probe amplification
    PARACLINICAL

 revealed a

    duplication mutation in exons 37-44 in the Dystrophin gene
    GENETICS

.

The present case report helps to better understand the clinical and genetic features of

    BMD
    DIAGNOSIS

.

Becker muscular dystrophy (BMD)
BMD
BMD
BMD
muscular dystrophy
BMD

gradually progressive muscle weakness
Epilepsy
dysgnosia
epilepsy
dysgnosia
low intelligence quotient (IQ = 65)
slight myogenic changes


Usefulness of continuous actigraph monitoring in the assessment of the effect of corticosteroid treatment for Duchenne muscular dystrophy: a case report.

[Purpose] This study evaluated the effect of corticosteroid treatment on the daily activity of a patient with Duchenne muscular dystrophy using an actigraph and examined whether this method produces the same results as the conventional motor-function evaluation methods. [Subject and Methods] A patient with 5 year-old Duchenne muscular dystrophy was recruited. An actigraph was attached to his waist to measure the energy expenditure and the number of steps taken by him during a period of two weeks, 14 days before and 14 days after corticosteroid administration. The outcomes of these measurements were compared with the results of conventional motor-function evaluation methods-the 10-m run test, 6-minute walk test, and North Star Ambulatory Assessment-on his next visit. [Results] The actigraph data for energy expenditure and the number of steps taken correlated well with the results of the above-mentioned conventional motor-function tests, and the value of each data point improved after corticosteroid administration. [Conclusion] An actigraph was effectively used to non-invasively measure consecutive daily activity for four weeks. It was easily done and the results were consistent with conventional motor-function evaluation methods.

[Purpose] This study evaluated the effect of

    corticosteroid treatment
    MEDICATION

 on the daily activity of a patient with

    Duchenne muscular dystrophy
    DIAGNOSIS

 using an

    actigraph
    PARACLINICAL

 and examined whether this method produces the same results as the conventional

    motor-function evaluation methods
    PARACLINICAL

. [Subject and Methods] A patient with

    5 year-old
    AGE

    Duchenne muscular dystrophy
    DIAGNOSIS

 was recruited. An

    actigraph was attached to his waist to measure the energy expenditure and the number of steps taken by him during a period of two weeks
    PARACLINICAL

, 14 days before and 14 days after

    corticosteroid administration
    MEDICATION

. The outcomes of these measurements were compared with the results of

    conventional motor-function evaluation methods-the 10-m run test
    PARACLINICAL

,

    6-minute walk test
    PARACLINICAL

, and

    North Star Ambulatory Assessment
    PARACLINICAL

-on his next visit. [Results] The

    actigraph data for energy expenditure and the number of steps taken
    PARACLINICAL

 correlated well with the results of the above

    -mentioned conventional motor-function tests
    PARACLINICAL

, and the value of each data point improved after

    corticosteroid administration
    MEDICATION

. [Conclusion] An

    actigraph
    PARACLINICAL

 was effectively used to

    non-invasively measure consecutive daily activity for four weeks
    PARACLINICAL

. It was easily done and the results were consistent with conventional

    motor-function evaluation methods
    PARACLINICAL

.

corticosteroid treatment
corticosteroid administration
corticosteroid administration


A case report with the peculiar concomitance of 2 different genetic syndromes.

Down syndrome (DS) is the most common chromosome disorder in live born infants, affecting several body systems, but usually sparing skeletal muscles. We present the case of a child with coexistence of DS and dystrophinopathy. Only 1 similar case has been reported so far.

An 8-year-old boy with DS had a history of incidental finding of increased serum creatine kinase levels up to 1775 U/L (normal values 38-174 U/L). He presented no delay in motor development; at the neurological examination, no muscle weakness or fatigability was detected in 2 different evaluations performed over a 6-month period.

Skeletal muscle biopsy revealed marked dystrophic changes with patchy immunostaining for dystrophin. The Duchenne muscular dystrophy gene was screened for deletions by multiplex polymerase chain reaction, but no mutations were found. Sequence analysis of the Duchenne muscular dystrophy gene revealed a splice-site mutation c.1812+1G>A in intron 15 and confirmed a diagnosis of Becker muscular dystrophy.

The patient has started a specific physiotherapy that avoided any deterioration in motor development and muscular wasting.

A multidisciplinary follow-up was initiated. The genetician that followed the patient for DS was supported by the neurologist, the physiotherapist, the pulmonologist, and the cardiologist.

This peculiar "double trouble" case exemplifies the value of careful clinical evaluation and adequate clinical experience to identify the concomitance of 2 different genetic syndromes in the same patient, and it points out the significance of muscular strength assessment in DS patients to make the most correct prognosis, and, consequently, to organize the best long-term care.

    Down syndrome (DS)
    DIAGNOSIS

 is the most common

    chromosome disorder
    DIAGNOSIS

 in

    live born infants
    AGE

,

    affecting several body systems
    SYMPTOMS

, but usually

    sparing skeletal muscles
    SYMPTOMS

. We present the case of a

    child
    AGE

 with

    coexistence of DS and dystrophinopathy
    DIAGNOSIS

. Only 1 similar case has been reported so far.

An

    8-year-old
    AGE

    boy
    GENDER

 with

    DS
    DIAGNOSIS

 had a history of incidental finding of

    increased serum creatine kinase levels up to 1775 U/L (normal values 38-174 U/L)
    BIOCHEMICAL

.

    He
    GENDER

 presented

    no delay in motor development
    NEG_FINDINGS

; at the

    neurological examination
    PARACLINICAL

,

    no muscle weakness or fatigability was detected
    NEG_FINDINGS

 in 2 different evaluations performed over a 6-month period.

    Skeletal muscle biopsy
    PARACLINICAL

 revealed

    marked dystrophic changes
    SYMPTOMS

 with

    patchy immunostaining for dystrophin
    MICROSCOPIC

. The

    Duchenne muscular dystrophy gene
    DIAGNOSIS

 was

    screened for deletions
    PARACLINICAL

 by

    multiplex polymerase chain reaction
    PARACLINICAL

, but

    no mutations were found
    NEG_FINDINGS

.

    Sequence analysis of the Duchenne muscular dystrophy
    PARACLINICAL

    gene
    PARACLINICAL

 revealed a

    splice-site mutation c.1812+1G>A in intron 15
    GENETICS

 and confirmed a diagnosis of

    Becker muscular dystrophy
    DIAGNOSIS

.

The patient has started a

    specific physiotherapy
    MEDICATION

 that

    avoided any deterioration in motor development and muscular wasting
    NEG_FINDINGS

.

A

    multidisciplinary follow-up
    MEDICATION

 was initiated. The

    genetician
    PARACLINICAL

 that followed the patient for

    DS
    DIAGNOSIS

 was supported by the

    neurologist
    PARACLINICAL

, the

    physiotherapist
    PARACLINICAL

, the

    pulmonologist
    PARACLINICAL

, and the

    cardiologist
    PARACLINICAL

.

This peculiar "

    double trouble"
    SYMPTOMS

 case exemplifies the value of

    careful clinical evaluation
    PARACLINICAL

 and adequate clinical experience to identify the

    concomitance of 2 different genetic syndromes
    FAMILY

 in the same patient, and it points out the significance of

    muscular strength assessment
    PARACLINICAL

 in

    DS
    DIAGNOSIS

 patients to make the most correct prognosis, and, consequently, to organize the best long-term care.

Down syndrome (DS)
chromosome disorder
coexistence of DS and dystrophinopathy
DS
Duchenne muscular dystrophy gene
Becker muscular dystrophy
DS
DS

affecting several body systems
sparing skeletal muscles
marked dystrophic changes
double trouble"

specific physiotherapy
multidisciplinary follow-up


The Limb-Girdle Muscular Dystrophies and the Dystrophinopathies.

The classic approach to identifying and accurately diagnosing limb-girdle muscular dystrophies (LGMDs) relied heavily on phenotypic characterization and ancillary studies including muscle biopsy. Because of rapid advances in genetic sequencing methodologies, several additional LGMDs have been molecularly characterized, and the diagnostic approach to these disorders has been simplified. This article summarizes the epidemiology, clinical features, and genetic defects underlying the LGMDs.

In recent years, the advent of next-generation sequencing has heralded an era of molecular diagnosis in conjunction with physical characterization. Inadvertently, this process has also led to the "next-generation aftermath," whereby variants of unknown significance are identified in most patients. Similar to the published diagnostic and treatment guidelines for Duchenne muscular dystrophy, diagnostic and treatment guidelines have recently been published for LGMDs. In addition, the first medication (based on the exon-skipping strategy) for treatment of patients with a subset of Duchenne muscular dystrophy has been recently approved by the US Food and Drug Administration (FDA).

The LGMDs are a heterogeneous group of hereditary, progressive, and degenerative neuromuscular disorders that present with primary symptoms of shoulder girdle and pelvic girdle weakness. Although a combination of clinical and molecular genetic evaluations may be sufficient for accurate diagnosis of LGMDs in many cases, the contribution of imaging and histopathologic correlations still remains a critical, if not a necessary, component of evaluation in some cases.

The classic approach to identifying and accurately diagnosing

    limb-girdle muscular dystrophies (LGMDs
    DIAGNOSIS

) relied heavily on phenotypic characterization and

    ancillary studies
    PARACLINICAL

 including

    muscle biopsy
    PARACLINICAL

. Because of rapid advances in genetic sequencing methodologies, several additional

    LGMDs
    DIAGNOSIS

 have been molecularly characterized, and the diagnostic approach to these disorders has been simplified. This article summarizes the epidemiology, clinical features, and genetic defects underlying the

    LGMDs
    DIAGNOSIS

.

In recent years, the advent of next-generation sequencing has heralded an era of

    molecular diagnosis
    PARACLINICAL

 in conjunction with

    physical characterization
    PARACLINICAL

. Inadvertently, this process has also led to the "next-generation aftermath," whereby variants of unknown significance are identified in most patients. Similar to the published diagnostic and treatment guidelines for

    Duchenne muscular dystrophy
    DIAGNOSIS

, diagnostic and treatment guidelines have recently been published for

    LGMDs
    DIAGNOSIS

. In addition, the first

    medication (based on the exon-skipping strategy)
    MEDICATION

 for treatment of patients with a subset of

    Duchenne muscular dystrophy
    DIAGNOSIS

 has been recently approved by the US Food and Drug Administration (FDA).

The

    LGMDs
    DIAGNOSIS

 are a heterogeneous group of

    hereditary
    GENETICS

    , progressive, and degenerative neuromuscular disorders
    DIAGNOSIS

 that present with

    primary symptoms of shoulder girdle and pelvic girdle weakness
    SYMPTOMS

. Although a combination of clinical and

    molecular genetic evaluations
    PARACLINICAL

 may be sufficient for accurate diagnosis of

    LGMDs
    DIAGNOSIS

 in many cases, the contribution of

    imaging and histopathologic correlations
    PARACLINICAL

 still remains a critical, if not a necessary, component of evaluation in some cases.


[Magnetic resonance imaging of dystrophinopathy that mimics adductor enthesopathy].

To report thigh muscle magnetic resonance imaging (MRI) tests of four Chinese patients with dystrophinopathy with edema changes in adductor longus muscles that mimics adductor enthesopathy.

Four boys, who were from four unrelated families and aged from 5 to 11 years, were investigated because of the clinical manifestations including myalgia or muscle weakness or the incidental findings of elevated serum creatine kinase levels, and were diagnosed with dystrophinopathy by gene test of Duchenne muscular dystrophy (DMD). Their creatine kinase levels were increased from 4 087 IU/L to 32 700 IU/L (Normal range: 75-175 IU/L). The muscle biopsy of three patients all demonstrated a dystrophic pattern including necrosis, regeneration, hypertrophy, atrophy and connective tissue proliferation, with different proportions of dystrophin-negative muscle fibers. The gene test of DMD showed an out-frame deletion of exons in three of the four patients, involving either exons 45 or exons 49-52 deletion or exon 62 duplication, and c.2665 C>T with nonsense mutation in the other one. Muscle MRI tests of the bilateral thighs were performed with T1 weighed sequence and slow tau inversion recovery sequence. The degree of fatty infiltration changes was scored.

MRI of the thigh muscles showed mild to severe fatty infiltration changes in T1 weighed sequence with the total scores from 2 to 13.The most severe fatty infiltration changes were in the long head of biceps femoris and adductor magnus. Obvious hyperintensities appeared mainly in the adductor longus muscles on slow tau inversion recovery (STIR) images in all the patients without any abnormal signals in the attachment of the ligament, indicating edema changes of the adductor longus muscles which mimiced adductor enthesopathy. Two of the four patients presented with edema changes in the bilateral adductor longus muscles, while the other two were with only unilateral changes. Furthermore, other thigh muscles, including adductor magnus, semitendinosus, sartorius and rectus femoris muscles, could also have mild edema changes in two of the four patients.

Dystrophinopathy can manifest as edema changes in the adductor longus muscles in thigh muscle MRI tests, which is a typical lesion in adductor enthesopathy. The adductor longus muscles in the dystrophinopathy patients may be easy to be impaired due to traction injury during sports.

To report

    thigh muscle magnetic resonance imaging (MRI) tests
    PARACLINICAL

 of four

    Chinese
    ETHNICITY

 patients with

    dystrophinopathy
    DIAGNOSIS

 with

    edema changes in adductor longus muscles
    SYMPTOMS

 that

    mimics adductor enthesopathy
    SYMPTOMS

.

Four

    boys
    GENDER

, who were from four unrelated families and

    aged from 5 to 11 years
    AGE

, were investigated because of the clinical manifestations including

    myalgia
    SYMPTOMS

 or

    muscle weakness
    SYMPTOMS

 or the incidental findings of

    elevated serum creatine kinase levels
    BIOCHEMICAL

, and were diagnosed with

    dystrophinopathy
    DIAGNOSIS

 by

    gene test
    PARACLINICAL

 of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Their

    creatine kinase levels were increased from 4 087 IU/L to 32 700 IU/L (Normal range: 75-175 IU/L)
    BIOCHEMICAL

. The

    muscle biopsy
    PARACLINICAL

 of three patients all demonstrated a

    dystrophic pattern including necrosis, regeneration, hypertrophy, atrophy and connective tissue proliferation
    MICROSCOPIC

, with

    different proportions of dystrophin-negative muscle fibers
    MICROSCOPIC

. The

    gene test of DMD
    PARACLINICAL

 showed an

    out-frame deletion of exons in
    GENETICS

 three of the four patients

    , involving either exons 45 or exons 49-52 deletion or exon 62 duplication
    GENETICS

, and

    c.2665 C>T with nonsense mutation
    GENETICS

 in the other one.

    Muscle MRI tests of the bilateral thighs
    PARACLINICAL

 were performed with

    T1 weighed sequence
    PARACLINICAL

 and slow tau inversion recovery sequence. The

    degree of fatty infiltration changes
    SYMPTOMS

 was scored.

    MRI of the thigh muscles
    PARACLINICAL

 showed

    mild to severe fatty infiltration changes
    SYMPTOMS

 in

    T1 weighed sequence
    PARACLINICAL

 with the total scores from 2 to 13.The

    most severe fatty infiltration changes were in the long head of biceps femoris and adductor magnus
    SYMPTOMS

.

    Obvious hyperintensities appeared mainly in the adductor longus muscles
    SYMPTOMS

 on slow tau inversion recovery (STIR) images in all the patients

    without any abnormal signals in the attachment of the ligament
    NEG_FINDINGS

, indicating

    edema changes of the adductor longus muscles
    SYMPTOMS

 which mimiced

    adductor enthesopathy
    DIAGNOSIS

. Two of the four patients presented with

    edema changes in the bilateral adductor longus muscles
    SYMPTOMS

, while the other two were with

    only unilateral changes
    SYMPTOMS

. Furthermore,

    other thigh muscles, including adductor magnus, semitendinosus, sartorius and rectus femoris muscles
    SYMPTOMS

,

    could also have mild edema changes
    SYMPTOMS

 in two of the four patients.

    Dystrophinopathy
    DIAGNOSIS

 can manifest as

    edema changes in the adductor longus muscles
    SYMPTOMS

 in

    thigh muscle MRI tests
    PARACLINICAL

, which is a typical lesion in

    adductor enthesopathy
    DIAGNOSIS

. The

    adductor longus muscles
    NEG_FINDINGS

 in the

    dystrophinopathy
    DIAGNOSIS

 patients may be easy to

    be impaired
    SYMPTOMS

 due to

    traction injury
    SYMPTOMS

 during

    sports
    SYMPTOMS

.

dystrophinopathy
dystrophinopathy
Duchenne muscular dystrophy (DMD)
adductor enthesopathy
Dystrophinopathy
adductor enthesopathy
dystrophinopathy


Becker muscular dystrophy due to an intronic splicing mutation inducing a dual dystrophin transcript.

We describe a 29-year-old patient who complained of left thigh muscle weakness since he was 23 and of moderate proximal weakness of both lower limbs with difficulty in climbing stairs and running since he was 27. Mild weakness of iliopsoas and quadriceps muscles and muscle atrophy of both the distal forearm and thigh were observed upon clinical examination. He harboured a novel c.1150-3C>G substitution in the DMD gene, affecting the intron 10 acceptor splice site and causing exon 11 skipping and an out-of-frame transcript. However, protein of normal molecular weight but in reduced amounts was observed on Western Blot analysis. Reverse transcription analysis on muscle RNA showed production, via alternative splicing, of a transcript missing exon 11 as well as a low abundant full-length transcript which is enough to avoid the severe Duchenne phenotype. Our study showed that a reduced amount of full length dystrophin leads to a mild form of Becker muscular dystrophy. These results confirm earlier findings that low amounts of dystrophin can be associated with a milder phenotype, which is promising for therapies aiming at dystrophin restoration.

We describe a

    29-year-old
    AGE

 patient who complained of

    left thigh muscle weakness
    SYMPTOMS

 since

    he was 23
    AGE

 and of

    moderate proximal weakness of both lower limbs
    SYMPTOMS

 with

    difficulty in climbing stairs and running
    SYMPTOMS

 since

    he was 27
    AGE

.

    Mild weakness of iliopsoas and quadriceps muscles
    SYMPTOMS

 and

    muscle atrophy of both the distal forearm and thigh
    SYMPTOMS

 were observed upon

    clinical examination
    PARACLINICAL

.

    He
    GENDER

 harboured a

    novel c.1150-3C>G substitution in the DMD gene, affecting the intron 10 acceptor splice site and causing exon 11 skipping and an out-of-frame transcript
    GENETICS

. However,

    protein of normal molecular weight but in reduced amounts
    BIOCHEMICAL

 was observed on

    Western Blot analysis
    PARACLINICAL

.

    Reverse transcription analysis on muscle RNA
    PARACLINICAL

 showed production, via

    alternative splicing, of a transcript missing exon 11 as well
    GENETICS

 as a

    low abundant full-length transcript
    BIOCHEMICAL

 which is enough to avoid the

    severe Duchenne
    DIAGNOSIS

 phenotype. Our study showed that a

    reduced amount of full length dystrophin
    BIOCHEMICAL

 leads to a

    mild form of Becker muscular dystrophy
    DIAGNOSIS

. These results confirm earlier findings that

    low amounts of dystrophin
    BIOCHEMICAL

 can be associated with a milder phenotype, which is promising for therapies aiming at

    dystrophin restoration
    MEDICATION

.

severe Duchenne
mild form of Becker muscular dystrophy


Diagnosis and treatment of obsessive compulsive behavior in a boy with Duchenne muscular dystrophy and autism spectrum disorder: A case report.

We describe a case study of comorbid obsessive-compulsive disorder (OCD) in a nine-year-old boy with Duchenne muscular dystrophy (DMD). Patient history included persistent deficits in social communication and restrictive and repetitive patterns of behavior: a diagnosis of autism spectrum was formalized. Due to serious disruption on social functioning and negative development of the obsessive behavior we decided to start pharmacotherapy. Fluoxetine 5 mg/day was started and gradually increased to 20 mg/day. A significant positive effect was observed by both parents and teacher in daily functioning. Although parents reported a positive change in mood, formal behavior rating by them did not reveal a significant effect, reflecting the insensitivity of general behavior rating scales. However, neuropsychological testing revealed a significant effect. This case report highlights the diagnostic and therapeutic challenges of complex neuropsychiatric comorbidities in DMD. It is the first scientific report on fluoxetine effectiveness in this patient group. Further research is needed.

We describe a case study of

    comorbid obsessive-compulsive disorder (OCD)
    DIAGNOSIS

 in a

    nine-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Patient history included

    persistent deficits in social communication
    SYMPTOMS

 and

    restrictive and repetitive patterns of behavior
    SYMPTOMS

: a diagnosis of

    autism spectrum
    DIAGNOSIS

 was formalized. Due to

    serious disruption on social functioning
    SYMPTOMS

 and

    negative development of the obsessive behavior
    SYMPTOMS

 we decided to start

    pharmacotherapy
    MEDICATION

.

    Fluoxetine 5 mg/day
    MEDICATION

 was started and

    gradually increased to 20 mg/day
    MEDICATION

. A

    significant positive effect
    SYMPTOMS

 was observed by both parents and teacher

    in daily functioning
    SYMPTOMS

. Although parents reported a

    positive change in mood
    SYMPTOMS

,

    formal behavior rating by them did not reveal a significant effect
    PARACLINICAL

, reflecting the

    insensitivity of general behavior rating scales
    NEG_FINDINGS

. However,

    neuropsychological testing
    PARACLINICAL

 revealed a significant effect. This case report highlights the diagnostic and therapeutic challenges of

    complex neuropsychiatric comorbidities
    DIAGNOSIS

 in

    DMD
    DIAGNOSIS

. It is the first scientific report on

    fluoxetine
    MEDICATION

 effectiveness in this patient group. Further research is needed.

pharmacotherapy
Fluoxetine 5 mg/day
gradually increased to 20 mg/day
fluoxetine


Recurrent Fat Embolic Strokes in a Patient With Duchenne Muscular Dystrophy With Long Bone Fractures and a Patent Foramen Ovale.

Individuals with Duchenne muscular dystrophy have an increased risk of long bone fractures. Such fractures are sometimes associated with brain dysfunction due to fat embolism syndrome, although this syndrome has seldom been documented in muscular dystrophy patients.

We describe a child with Duchenne muscular dystrophy who developed fat embolism syndrome with neurological dysfunction following multiple long bone fractures. He experienced recurrent cerebral infarctions that probably resulted from embolization through a patent foramen ovale. The patent foramen ovale was closed by an occluder device in the cardiac catheterization laboratory, and he did not experience further infarctions.

Fat embolism with ischemic cerebral infarction can occur in individuals with Duchenne muscular dystrophy following long bone fractures. In this setting it is important to identify and close atrial level shunts in order to prevent additional infarctions.

Individuals with

    Duchenne muscular dystrophy
    DIAGNOSIS

 have an increased risk of

    long bone fractures
    SYMPTOMS

. Such fractures are sometimes associated with

    brain dysfunction
    SYMPTOMS

 due to

    fat embolism syndrome
    SYMPTOMS

, although this syndrome has seldom been documented in

    muscular dystrophy
    DIAGNOSIS

 patients.

We describe a

    child
    AGE

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who developed

    fat embolism syndrome
    SYMPTOMS

 with

    neurological dysfunction
    SYMPTOMS

 following

    multiple long bone fractures
    SYMPTOMS

.

    He
    GENDER

 experienced

    recurrent cerebral infarctions
    SYMPTOMS

 that probably resulted from

    embolization through a patent foramen ovale
    SYMPTOMS

. The

    patent foramen ovale was closed by an occluder device
    MEDICATION

 in the

    cardiac catheterization laboratory
    MEDICATION

, and

    he
    GENDER

    did not experience further infarctions
    NEG_FINDINGS

.

    Fat embolism
    SYMPTOMS

 with

    ischemic cerebral infarction
    SYMPTOMS

 can occur in individuals with

    Duchenne muscular dystrophy
    DIAGNOSIS

 following

    long bone fractures
    MEDICATION

. In this setting it is important to identify and

    close atrial level shunts
    MEDICATION

 in order to prevent

    additional infarctions
    SYMPTOMS

.

Duchenne muscular dystrophy
muscular dystrophy
Duchenne muscular dystrophy
Duchenne muscular dystrophy


Effects of teriparatide on bone mineral density and quality of life in Duchenne muscular dystrophy related osteoporosis: a case report.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by secondary osteoporosis and increased fractures. We describe the case of a 20-year-old boy with DMD suffering from back pain due to multiple vertebral fractures who was treated with teriparatide. Improvement of bone density, pain, and quality of life was achieved. DMD is an X-linked recessive muscle disease with secondary osteoporosis and related frequently occurring fractures. To date, only bisphosphonates have been used to treat osteoporosis in DMD. Black bear parathyroid hormone has been previously reported to enhance bone mass in the dystrophin-deficient mouse. This study reports the positive effect of osteoanabolic treatment with once-daily recombinant human parathyroid hormone 1-34 (rhPTH 1-34, teriparatide) in a 20-year-old DMD boy suffering from multiple vertebral fractures causing back pain. Bone formation and resorption markers (osteocalcin and C-telopeptide of type I collagen, respectively), as expected, increased within 6 months and intensity of back pain early decreased, with no pain reported after 6 months at visual analog scale. Over a 18-month period of treatment with teriparatide, bone mineral density and quality of life, assessed by the 36-item short-form questionnaire, considerably improved and no side effects were reported. Further studies on large cohorts are warranted to test the efficacy of this promising treatment for DMD related osteoporosis.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is an

    X-linked recessive muscle disease
    GENETICS

 characterized by

    secondary osteoporosis
    SYMPTOMS

 and

    increased fractures
    SYMPTOMS

. We describe the case of a

    20-year-old
    AGE

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 suffering from

    back pain
    SYMPTOMS

 due to

    multiple vertebral fractures
    SYMPTOMS

 who was treated with

    teriparatide
    MEDICATION

.

    Improvement of bone density, pain, and quality of life
    SYMPTOMS

 was achieved.

    DMD
    DIAGNOSIS

 is an

    X-linked recessive muscle disease
    GENETICS

 with

    secondary osteoporosis
    SYMPTOMS

 and related

    frequently occurring fractures
    SYMPTOMS

. To date, only

    bisphosphonates
    MEDICATION

 have been used to treat

    osteoporosis
    DIAGNOSIS

 in

    DMD
    DIAGNOSIS

.

    Black bear parathyroid hormone
    MEDICATION

 has been previously reported to

    enhance bone mass
    SYMPTOMS

 in the

    dystrophin-deficient
    GENETICS

 mouse. This study reports the positive effect of

    osteoanabolic treatment with once-daily recombinant human parathyroid hormone 1-34 (rhPTH 1-34, teriparatide)
    MEDICATION

 in a

    20-year-old
    AGE

    DMD
    DIAGNOSIS

    boy
    GENDER

 suffering from

    multiple vertebral fractures
    SYMPTOMS

 causing

    back pain
    SYMPTOMS

.

    Bone formation and resorption markers (osteocalcin and C-telopeptide of type I collagen, respectively), as expected, increased within 6 months
    BIOCHEMICAL

 and

    intensity of back pain early decreased
    SYMPTOMS

, with

    no pain reported after 6 months at visual analog scale
    NEG_FINDINGS

. Over a

    18-month period of treatment with teriparatide
    MEDICATION

,

    bone mineral density and quality of life
    SYMPTOMS

, assessed by the 36-item short-form questionnaire,

    considerably improved
    SYMPTOMS

 and

    no side effects
    NEG_FINDINGS

 were reported. Further studies on large cohorts are warranted to test the efficacy of this promising treatment for

    DMD related osteoporosis
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
DMD
osteoporosis
DMD
DMD
DMD related osteoporosis

X-linked recessive muscle disease
X-linked recessive muscle disease
dystrophin-deficient


A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

The patient was a

    26 year-old
    AGE

    man
    GENDER

 who was referred to our hospital in June 2011 because of

    severe heart failure
    SYMPTOMS

. At

    age 24 years
    AGE

,

    he
    GENDER

 was found to have

    Becker muscular dystrophy
    DIAGNOSIS

.

    He
    GENDER

 received

    enalapril
    MEDICATION

 for

    cardiac dysfunction
    SYMPTOMS

; however,

    he
    GENDER

 had

    worsening heart failure
    SYMPTOMS

 and was thus referred to our hospital.

    Echocardiography
    PARACLINICAL

 showed

    enlargement of the left ventricle, with a diastolic dimension of 77 mm
    SYMPTOMS

 and

    ejection fraction of 19%
    SYMPTOMS

. His condition improved temporarily after an

    infusion of dobutamine and milrinone
    MEDICATION

.

    He
    GENDER

 was then administered

    amiodarone
    MEDICATION

 for

    ventricular tachycardia
    SYMPTOMS

; however,

    he
    GENDER

 subsequently developed

    hemoptysis
    SYMPTOMS

.

    Amiodarone
    NEG_FINDINGS

    was discontinued
    MEDICATION

 and

    corticosteroid pulse therapy was administered followed by oral prednisolone (PSL)
    MEDICATION

. His

    creatinine phosphokinase (CPK) level
    BIOCHEMICAL

 and

    cardiomegaly
    SYMPTOMS

    improved
    BIOCHEMICAL

 after the

    corticosteroid therapy
    MEDICATION

. The

    PSL dose was reduced gradually
    MEDICATION

,

    bisoprolol was introduced
    MEDICATION

, and

    the catecholamine infusion was tapered
    MEDICATION

. A

    cardiac resynchronization device was implanted
    MEDICATION

; however, the patient's condition gradually worsened, which necessitated

    dobutamine infusion
    MEDICATION

 for

    heart failure
    SYMPTOMS

. We

    readministered 30 mg PSL
    MEDICATION

, which

    decreased the CPK level
    BIOCHEMICAL

 and

    improved the cardiomegaly
    SYMPTOMS

.

    The dobutamine infusion was discontinued
    MEDICATION

, and the patient was

    discharged
    MEDICATION

. He was

    given 7.5 mg PSL as an outpatient
    MEDICATION

, and he returned to normal life

    without exacerbation of the heart failure
    NEG_FINDINGS

. There are similar reports showing that

    corticosteroids
    MEDICATION

 are effective for

    skeletal muscle improvement
    SYMPTOMS

 in

    Duchenne muscular dystrophy
    DIAGNOSIS

; however, their effectiveness for

    heart failure
    DIAGNOSIS

 has been rarely reported. We experienced a case of

    Becker muscular dystrophy
    DIAGNOSIS

 in which

    corticosteroid therapy
    MEDICATION

 was effective for

    refractory heart failure
    SYMPTOMS

.

Becker muscular dystrophy
Duchenne muscular dystrophy
heart failure
Becker muscular dystrophy

creatinine phosphokinase (CPK) level
improved
decreased the CPK level


Duchenne muscular dystrophy caused by a frame-shift mutation in the acceptor splice site of intron 26.

The dystrophin gene is the one of the largest described in human beings and mutations associated to this gene are responsible for Duchenne or Becker muscular dystrophies.

Here we describe a nucleotide substitution in the acceptor splice site of intron 26 (c.3604-1G > C) carried by a 6-year-old boy who presented with a history of progressive proximal muscle weakness and elevated serum creatine kinase levels. RNA analysis showed that the first two nucleotides of the mutated intron 26 (AC) were not recognized by the splicing machinery and a new splicing site was created within exon 27, generating a premature stop codon and avoiding protein translation.

The evaluation of the pathogenic effect of the mutation by mRNA analysis will be useful in the optics of an antisense oligonucleotides (AON)-based therapy.

    The dystrophin gene
    GENETICS

 is the one of the largest described in human beings and

    mutations associated to this gene
    GENETICS

 are responsible for

    Duchenne or Becker muscular dystrophies
    DIAGNOSIS

.

Here we describe a

    nucleotide substitution in the acceptor splice site of intron 26 (c.3604-1G > C)
    GENETICS

 carried by a

    6-year-old
    AGE

    boy
    GENDER

 who presented with a history of

    progressive proximal muscle weakness
    SYMPTOMS

 and

    elevated serum creatine kinase levels
    BIOCHEMICAL

.

    RNA analysis
    PARACLINICAL

 showed that

    the first two nucleotides of the mutated intron 26 (AC) were not recognized by the splicing machinery and a new splicing site was created within exon 27, generating a premature stop codon and avoiding protein translation
    GENETICS

.

The evaluation of the pathogenic effect of the mutation by

    mRNA analysis
    PARACLINICAL

 will be useful in the optics of an

    antisense oligonucleotides (AON)-based therapy
    MEDICATION

.


A dynamic trinucleotide repeat (TNR) expansion in the DMD gene.

Dystrophinopathies are allelic X-linked myopathies caused by large deletions/duplications or small lesions along the DMD gene. An unexpected dynamic trinucleotide (GAA) expansion, ranging from ∼59 to 82 pure GAA repeats, within the DMD intron 62, was revealed to segregate through three family generations. From the pedigree, two female patients were referred for DMD investigation due to chronic myopathy and a muscle biopsy compatible with dystrophinopathy. As the size of the GAA repeat is limited to 11-33 within the general population our findings may provide a novel insight towards a Trinucleotide Repeat Expansion. Whether this TNR has an impact on the reported phenotype remains to be resolved.

    Dystrophinopathies
    DIAGNOSIS

 are

    allelic X-linked
    GENETICS

    myopathies
    DIAGNOSIS

 caused by

    large deletions/duplications or small lesions along the DMD gene
    GENETICS

. An

    unexpected dynamic trinucleotide (GAA) expansion, ranging from ∼59 to 82 pure GAA repeats, within the DMD intron 62
    GENETICS

, was revealed to segregate through three family generations. From the pedigree, two

    female
    GENDER

 patients were referred for

    DMD
    DIAGNOSIS

 investigation due to

    chronic myopathy
    DIAGNOSIS

 and a

    muscle biopsy
    PARACLINICAL

 compatible with

    dystrophinopathy
    DIAGNOSIS

. As the

    size of the GAA repeat is limited to 11-33 within the general population
    GENETICS

 our findings may provide a novel insight towards a

    Trinucleotide Repeat Expansion
    GENETICS

. Whether this

    TNR
    GENETICS

 has an impact on the reported phenotype remains to be resolved.

Dystrophinopathies
myopathies
DMD
chronic myopathy
dystrophinopathy


A rare form of limb girdle muscular dystrophy (type 2E) seen in an Iranian family detected by autozygosity mapping.

Sarcoglycanopathies (SGPs) constitute a subgroup of autosomal recessive limb girdle muscular dystrophies (LGMDs) which are caused by mutations in sarcoglycan (SGs) genes. SG proteins form a core complex consisting of α, β, γ and δ sarcoglycans which are encoded by SGCA, SGCB, SGCG and SGCD genes, respectively. Genetic defect, in any of these SG proteins, results in instability of the whole complex. This effect can be helpful in interpreting muscle biopsy results. Autozygosity mapping is a gene mapping approach which can be applied in large consanguineous families for tracking the defective gene in most autosomal recessive disorders. In the present study, we used autozygosity mapping, to find the gene responsible for muscular dystrophy. Proband was a 10-year-old boy referred to our center for ruling out DMD (Duchenne muscular dystrophy). According to the pedigree and clinical reports, we assessed him for SGPs. Haplotyping, using the four short tandem repeat (STR) markers for each of the SG genes, showed that the phenotype may segregate with SGCB gene; and observing two crossing overs which occurred within the gene suggested that the mutation might be in the first two exons of SGCB gene. Mutation analysis showed a 26 bp duplication (10 bp before the initiation codon till 13 bp after the ATG start codon). This will cause a frameshift in protein synthesis.

    Sarcoglycanopathies (SGPs)
    DIAGNOSIS

 constitute a subgroup of

    autosomal recessive limb girdle muscular dystrophies (LGMDs)
    DIAGNOSIS

 which are caused by

    mutations in sarcoglycan (SGs) genes
    GENETICS

. SG proteins form a core complex consisting of α, β, γ and δ

    sarcoglycans
    BIOCHEMICAL

 which are encoded by

    SGCA, SGCB, SGCG and SGCD genes
    GENETICS

, respectively.

    Genetic defect, in any of these SG proteins
    GENETICS

, results in

    instability of the whole complex
    MICROSCOPIC

. This effect can be helpful in interpreting

    muscle biopsy
    PARACLINICAL

 results.

    Autozygosity mapping
    PARACLINICAL

 is a

    gene mapping approach
    PARACLINICAL

 which can be applied in large

    consanguineous families
    FAMILY

 for tracking the defective gene in most

    autosomal recessive disorders
    GENETICS

. In the present study, we used

    autozygosity mapping
    PARACLINICAL

, to find the gene responsible for

    muscular dystrophy
    DIAGNOSIS

. Proband was a

    10-year-old
    AGE

    boy
    GENDER

 referred to our center for

    ruling out DMD (Duchenne muscular dystrophy)
    NEG_FINDINGS

. According to the pedigree and clinical reports, we assessed

    him
    GENDER

 for

    SGPs
    DIAGNOSIS

.

    Haplotyping, using the four short tandem repeat (STR) markers for each of the SG genes
    PARACLINICAL

, showed that the

    phenotype may segregate with SGCB gene
    GENETICS

; and

    observing two crossing overs which occurred within the gene
    GENETICS

 suggested that the

    mutation might be in the first two exons of SGCB gene
    GENETICS

.

    Mutation analysis
    PARACLINICAL

 showed a

    26 bp duplication (10 bp before the initiation codon till 13 bp after the ATG start codon)
    GENETICS

. This will cause a

    frameshift in protein synthesis
    GENETICS

.


[Application of spinal anesthesia in a pediatric patient with Duchenne's muscular dystrophy].

Duchenne's muscular dystrophy (DMD) is a neuromuscular disease with a progressive course. It is the most common and most severe muscular dystrophic disorder for which the application of anesthesia is critical, due to muscle weakness, and cardiac and pulmonary involvement. Successful application of spinal anesthesia in a 2-year-old boy with DMD undergoing bilateral inguinal hernia repair is described in the present report. It is proposed that spinal anesthesia is an effective alternative to general anesthesia in certain pediatric patients, including those with DMD, for whom general anesthesia poses increased risk.

    Duchenne's muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    neuromuscular disease
    DIAGNOSIS

 with a progressive course. It is the most common and most severe

    muscular dystrophic disorder
    DIAGNOSIS

 for which the application of

    anesthesia
    MEDICATION

 is critical, due to

    muscle weakness
    SYMPTOMS

, and

    cardiac and pulmonary involvement
    SYMPTOMS

. Successful

    application of spinal anesthesia
    MEDICATION

 in a

    2-year-old
    AGE

    boy
    GENDER

 with

    DMD
    DIAGNOSIS

 undergoing

    bilateral inguinal hernia repair
    MEDICATION

 is described in the present report. It is proposed that

    spinal anesthesia
    MEDICATION

 is an effective

    alternative to general anesthesia
    MEDICATION

 in certain

    pediatric
    AGE

 patients, including those with

    DMD
    DIAGNOSIS

, for whom

    general anesthesia
    MEDICATION

 poses increased risk.

Duchenne's muscular dystrophy (DMD)
neuromuscular disease
muscular dystrophic disorder
DMD
DMD

anesthesia
application of spinal anesthesia
bilateral inguinal hernia repair
spinal anesthesia
alternative to general anesthesia
general anesthesia

muscle weakness
cardiac and pulmonary involvement


Unique pattern of late gadolinium enhancement on cardiac magnetic resonance imaging in Duchenne muscular dystrophy.

Cardiomyopathy is an important cause of morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Early recognition of myocardial involvement and initiation of therapy are important for improved outcomes. Cardiac magnetic resonance imaging (CMR) is a sensitive tool in early detection of myocardial fibrosis in these children.

    Cardiomyopathy
    DIAGNOSIS

 is an important cause of morbidity and mortality in patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Early recognition of

    myocardial involvement
    SYMPTOMS

 and

    initiation of therapy
    MEDICATION

 are important for improved outcomes.

    Cardiac magnetic resonance imaging (CMR)
    PARACLINICAL

 is a sensitive tool in early detection of

    myocardial fibrosis
    SYMPTOMS

 in these

    children
    AGE

.

Cardiomyopathy
Duchenne muscular dystrophy (DMD)

myocardial involvement
myocardial fibrosis


Suspected acute myocardial infarction in a dystrophin-deficient dog.

Golden retriever muscular dystrophy (GRMD) is a model for the genetically homologous human disease, Duchenne muscular dystrophy (DMD). Unlike the mildly affected mdx mouse, GRMD recapitulates the severe DMD phenotype. In addition to skeletal muscle involvement, DMD boys develop cardiomyopathy. While the cardiomyopathy of DMD is typically slowly progressive, rare early episodes of acute cardiac decompensation, compatible with myocardial infarction, have been described. We report here a 7-month-old GRMD dog with an apparent analogous episode of myocardial infarction. The dog presented with acute signs of cardiac disease, including tachyarrhythmia, supraventricular premature complexes, and femoral pulse deficits. Serum cardiac biomarkers, cardiac-specific troponin I (cTnI) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), were markedly increased. Echocardiography showed areas of hyperechoic myocardial enhancement, typical of GRMD cardiomyopathy. Left ventricular dyskinesis and elevated cTnI were suggestive of acute myocardial damage/infarction. Over a 3-year period, progression to a severe dilated phenotype was observed.

    Golden retriever muscular dystrophy (GRMD)
    DIAGNOSIS

 is a model for the genetically homologous human disease,

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

. Unlike the mildly affected

    mdx
    DIAGNOSIS

 mouse,

    GRMD
    DIAGNOSIS

 recapitulates the

    severe DMD
    DIAGNOSIS

 phenotype. In addition to

    skeletal muscle involvement
    SYMPTOMS

,

    DMD
    DIAGNOSIS

    boys
    GENDER

 develop

    cardiomyopathy
    DIAGNOSIS

. While the

    cardiomyopathy
    DIAGNOSIS

 of

    DMD
    DIAGNOSIS

 is typically

    slowly progressive
    DIAGNOSIS

, rare

    early episodes of acute cardiac decompensation
    SYMPTOMS

, compatible with

    myocardial infarction
    SYMPTOMS

, have been described. We report here a

    7-month-old
    AGE

    GRMD
    DIAGNOSIS

    dog
    GENDER

 with an

    apparent analogous episode of myocardial infarction
    SYMPTOMS

. The

    dog
    GENDER

 presented with

    acute signs of cardiac disease
    SYMPTOMS

, including

    tachyarrhythmia
    SYMPTOMS

,

    supraventricular premature complexes
    SYMPTOMS

, and

    femoral pulse deficits
    SYMPTOMS

.

    Serum cardiac biomarkers, cardiac-specific troponin I (cTnI) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), were markedly increased
    BIOCHEMICAL

.

    Echocardiography
    PARACLINICAL

 showed

    areas of hyperechoic myocardial enhancement
    SYMPTOMS

, typical of

    GRMD cardiomyopathy
    DIAGNOSIS

.

    Left ventricular dyskinesis
    SYMPTOMS

 and

    elevated cTnI
    BIOCHEMICAL

 were suggestive of

    acute myocardial damage/infarction
    SYMPTOMS

. Over a 3-year period,

    progression to a severe dilated phenotype
    SYMPTOMS

 was observed.


[Enteral nutrition ameliorated superior mesenteric artery syndrome in a patient with Duchenne muscular dystrophy].

The abdominal complications of Duchenne muscular dystrophy (DMD) include acute gastric dilatation, superior mesenteric artery (SMA) syndrome, ileus and constipation. We report herein a patient with DMD in whom SMA syndrome was successfully treated with enteral tube nutrition. The patient was a 16-year-old boy diagnosed with DMD at 2 years. Steroid therapy was started at 5 years, and he was unable to walk and was wheelchair-bound at 11 years. Lordoscoliosis progressed after the age of 14 years. Noninvasive mechanical ventilation was introduced due to respiratory impairment at 15 years. During 8 months with respiratory impairment, his body weight decreased from 40.3 kg to 33.4 kg. He was referred to our hospital for vomiting and hematemesis. Radiographic studies indicated a diagnosis of SMA syndrome. Enteral nutrition with a nasojejunal tube successfully treated SMA syndrome for 5 months and his body weight increased from 32.7 kg to 36.1 kg. Gastrostomy was subsequently performed and no recurrence was evident. SMA syndrome is caused by compression of the third part of the duodenum at the angle between the aorta and SMA. The conditions for duodenal vascular compression are weight loss resulting in depletion of the retroperitoneal fat and progressive lordosis. The reasons for SMA syndrome with our patient were weight loss and progressive lordoscoliosis. A conservative approach with enteral nutrition promoted weight gain, increasing retroperitoneal fat. Enteral nutrition should be considered for the treatment of SMA syndrome as a complication of DMD.

The

    abdominal complications
    SYMPTOMS

 of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 include

    acute gastric dilatation
    SYMPTOMS

,

    superior mesenteric artery (SMA) syndrome
    SYMPTOMS

,

    ileus
    SYMPTOMS

 and

    constipation
    SYMPTOMS

. We report herein a patient with

    DMD
    DIAGNOSIS

 in whom

    SMA syndrome
    DIAGNOSIS

 was successfully treated with

    enteral tube nutrition
    MEDICATION

. The patient was a

    16-year-old
    AGE

    boy
    GENDER

 diagnosed with

    DMD
    DIAGNOSIS

    at 2 years
    AGE

.

    Steroid therapy
    MEDICATION

 was started

    at 5 years
    AGE

, and

    he
    GENDER

 was

    unable to walk
    NEG_FINDINGS

 and was

    wheelchair-bound
    MEDICATION

    at 11 years
    AGE

.

    Lordoscoliosis
    SYMPTOMS

 progressed

    after the age of 14 years
    AGE

.

    Noninvasive mechanical ventilation
    MEDICATION

 was introduced due to

    respiratory impairment
    SYMPTOMS

    at 15 years
    AGE

. During

    8 months
    AGE

 with

    respiratory impairment
    SYMPTOMS

, his

    body weight decreased from 40.3 kg to 33.4 kg
    SYMPTOMS

.

    He
    GENDER

 was referred to our hospital for

    vomiting
    SYMPTOMS

 and

    hematemesis
    SYMPTOMS

.

    Radiographic studies
    PARACLINICAL

 indicated a diagnosis of

    SMA syndrome
    DIAGNOSIS

.

    Enteral nutrition with a nasojejunal tube
    MEDICATION

 successfully treated

    SMA syndrome
    DIAGNOSIS

    for 5 months
    MEDICATION

 and his

    body weight increased from 32.7 kg to 36.1 kg
    SYMPTOMS

.

    Gastrostomy
    MEDICATION

 was subsequently performed and

    no recurrence was evident
    NEG_FINDINGS

.

    SMA syndrome
    DIAGNOSIS

 is caused by

    compression of the third part of the duodenum at the angle between the aorta and SMA
    SYMPTOMS

. The conditions for

    duodenal vascular compression
    SYMPTOMS

 are

    weight loss
    SYMPTOMS

 resulting in

    depletion of the retroperitoneal fat
    SYMPTOMS

 and

    progressive lordosis
    SYMPTOMS

. The reasons for

    SMA syndrome
    DIAGNOSIS

 with our patient were

    weight loss
    SYMPTOMS

 and

    progressive lordoscoliosis
    SYMPTOMS

. A

    conservative approach with enteral nutrition
    MEDICATION

 promoted

    weight gain
    SYMPTOMS

,

    increasing retroperitoneal fat
    SYMPTOMS

.

    Enteral nutrition
    MEDICATION

 should be considered for the treatment of

    SMA syndrome
    DIAGNOSIS

 as a complication of

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
SMA syndrome
DMD
SMA syndrome
SMA syndrome
SMA syndrome
SMA syndrome
SMA syndrome
DMD

unable to walk
no recurrence was evident