Elevated troponin T levels in a female carrier of Duchenne muscular dystrophy with normal coronary angiogram: a case report and review of the literature.

We present the case of a 48-year-old female carrier of Duchenne muscular dystrophy (DMD) with repeatedly documented levels of elevated troponin T without arguments for cardiac ischaemia. Elevated levels of troponin T are frequently reported in DMD patients and may function as a useful cardiac index to assess dystrophic degeneration of the myocardium in a subclinical stage. Cardiac troponins may help the clinician to diagnose myocardial damage in a very early stage of cardiac impairment independently from skeletal muscle degeneration.

We present the case of a

    48-year-old
    AGE

    female
    GENDER

 carrier of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 with

    repeatedly documented levels of elevated troponin T
    BIOCHEMICAL

    without arguments for cardiac ischaemia
    NEG_FINDINGS

.

    Elevated levels of troponin T
    BIOCHEMICAL

 are frequently reported in

    DMD
    DIAGNOSIS

 patients and may function as a useful cardiac index to assess

    dystrophic degeneration of the myocardium
    SYMPTOMS

 in a subclinical stage.

    Cardiac troponins
    BIOCHEMICAL

 may help the clinician to diagnose

    myocardial damage
    SYMPTOMS

 in a very early stage of

    cardiac impairment
    SYMPTOMS

 independently from

    skeletal muscle degeneration
    NEG_FINDINGS

.

without arguments for cardiac ischaemia
skeletal muscle degeneration


Dexmedetomidine-ketamine sedation during upper gastrointestinal endoscopy and biopsy in a patient with Duchenne muscular dystrophy and egg allergy.

Sedation during invasive procedures provides appropriate humanitarian care as well as facilitating the completion of procedure. Although generally safe and effective, adverse effects may occur especially in patients with co-morbid diseases. In many cases, given its rapid onset and offset, propofol is chosen to provide sedation during various invasive procedures. We present a nine-year-old, 45 kg child with Duchenne muscular dystrophy (DMD) who presented for esophagogastroduodenoscopy (EGD). Given the egg allergy, which was a relative contraindication to the use of propofol, and the potential risk of malignant hyperthermia due to DMD, a combination of dexmedetomidine and ketamine was used for procedural sedation. Dexmedetomidine was administered as a loading dose of 1 μg/kg along with a single bolus dose of ketamine (1 mg/kg). This was followed by a dexmedetomidine infusion at 0.5 μg/kg/hour. The patient tolerated the procedure well and was discharged to home. Previous reports regarding the use of dexmedetomidine and ketamine for procedural sedation are reviewed and the potential efficacy of this combination is discussed.

    Sedation
    MEDICATION

 during

    invasive procedures
    MEDICATION

 provides

    appropriate humanitarian care
    MEDICATION

 as well as facilitating the completion of procedure. Although generally safe and effective,

    adverse effects
    SYMPTOMS

 may occur especially in patients with

    co-morbid diseases
    SYMPTOMS

. In many cases, given its rapid onset and offset,

    propofol
    MEDICATION

 is chosen to provide

    sedation
    MEDICATION

 during various

    invasive procedures
    MEDICATION

. We present a

    nine-year-old
    AGE

,

    45 kg child
    AGE

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 who presented for

    esophagogastroduodenoscopy (EGD)
    PARACLINICAL

. Given the

    egg allergy
    NEG_FINDINGS

, which was a

    relative contraindication to the use of propofol
    NEG_FINDINGS

, and the potential risk of

    malignant hyperthermia
    DIAGNOSIS

 due to

    DMD
    DIAGNOSIS

, a

    combination of dexmedetomidine and ketamine was used for procedural sedation
    MEDICATION

.

    Dexmedetomidine was administered as a loading dose of 1 μg/kg along with a single bolus dose of ketamine (1 mg/kg)
    MEDICATION

. This was followed by

    a dexmedetomidine infusion at 0.5 μg/kg/hour
    MEDICATION

. The patient tolerated the procedure well and was

    discharged to home
    MEDICATION

. Previous reports regarding the

    use of dexmedetomidine and ketamine for procedural sedation
    MEDICATION

 are reviewed and the potential efficacy of this combination is discussed.

Duchenne muscular dystrophy (DMD)
malignant hyperthermia
DMD


Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype.

With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD associated with an exon 26 deletion. The proband, a 23-year-old man, had slightly delayed motor milestones, walking 1 1/2 years old. He had no complaints of muscle weakness, but had muscle pain. Clinical examination revealed no muscle wasting or loss of power, but his CK was 1500-7000 U/l. Muscle biopsy showed dystrophic changes. He had comorbidity with dystonia, slight mental retardation, low stature and neuropathy. The brother of the proband's mother came to medical attention when he was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+ hip extention palsy and a discrete calf hypertrophy was noted. Creatine kinase was normal or raised maximally to 500 U/l. The muscle biopsy was myopathic with increased fiber size variation and many internal nuclei, but no dystrophy. No comorbidity was found. In both cases, western blot showed a reduced dystrophin band. Genetic evaluation revealed a deletion of exon 26 of the dystrophin gene in both. This is the first description of patients with a exon 26 deletion of the dystrophin gene. Assuming the proband's comorbidity is unrelated, exon 26 deletion results in a very mild phenotype. This might be of interest in planning exon skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK.

With the possible introduction of

    exon skipping therapy
    MEDICATION

 in

    Duchenne muscular dystrophy
    DIAGNOSIS

, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related

    men
    GENDER

 with an

    unusually mild BMD
    DIAGNOSIS

 associated with an

    exon 26 deletion
    GENETICS

. The proband, a

    23-year-old
    AGE

    man
    GENDER

, had

    slightly delayed motor milestones
    SYMPTOMS

,

    walking 1 1/2 years old
    AGE

.

    He
    GENDER

 had

    no complaints of muscle weakness
    NEG_FINDINGS

, but had

    muscle pain
    SYMPTOMS

.

    Clinical examination
    PARACLINICAL

 revealed

    no muscle wasting or loss of power
    NEG_FINDINGS

, but

    his
    GENDER

 CK was 1500-7000 U/l.

    Muscle biopsy
    PARACLINICAL

 showed

    dystrophic changes
    SYMPTOMS

.

    He
    GENDER

 had

    comorbidity with dystonia
    FAMILY

,

    slight mental retardation
    SYMPTOMS

,

    low stature
    SYMPTOMS

 and

    neuropathy
    SYMPTOMS

. The

    brother of the proband's mother
    GENDER

 came to medical attention when

    he
    GENDER

 was

    43 years old
    AGE

.

    He
    GENDER

 complained about

    muscle pain
    SYMPTOMS

. On examination, a

    MRC grade 4+ hip extention palsy
    SYMPTOMS

 and a

    discrete calf hypertrophy
    SYMPTOMS

 was noted. Creatine kinase was normal or raised maximally to 500 U/l. The

    muscle biopsy
    PARACLINICAL

 was

    myopathic
    SYMPTOMS

 with

    increased fiber size variation and many internal nuclei
    MICROSCOPIC

, but

    no dystrophy
    NEG_FINDINGS

.

    No comorbidity was found
    NEG_FINDINGS

. In both cases,

    western blot
    PARACLINICAL

 showed a

    reduced dystrophin band
    BIOCHEMICAL

.

    Genetic evaluation
    PARACLINICAL

 revealed a

    deletion of exon 26 of the dystrophin gene
    GENETICS

 in both. This is the first description of patients with a

    exon 26 deletion of the dystrophin gene
    GENETICS

. Assuming the

    proband's comorbidity is unrelated
    FAMILY

,

    exon 26 deletion
    GENETICS

 results in a very mild phenotype. This might be of interest in planning

    exon skipping therapy
    MEDICATION

 for

    Duchenne muscular dystrophy
    DIAGNOSIS

. This report also shows that

    BMD
    DIAGNOSIS

 may present with a

    normal CK
    NEG_FINDINGS

.

exon skipping therapy
exon skipping therapy

Duchenne muscular dystrophy
unusually mild BMD
Duchenne muscular dystrophy
BMD

slightly delayed motor milestones
muscle pain
dystrophic changes
slight mental retardation
low stature
neuropathy
muscle pain
MRC grade 4+ hip extention palsy
discrete calf hypertrophy
myopathic

no complaints of muscle weakness
no muscle wasting or loss of power
no dystrophy
No comorbidity was found
normal CK


Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion.

We performed a long-term study of alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary outcome measure was prolongation of the ability to walk.

One patient lost ambulation at age 10. Four patients, aged 16 to 18 were fully ambulant, and 3 of them could still climb stairs. Respiratory function was moderately reduced in 2. Left ventricular ejection fraction was > 45%. Short stature and delayed puberty were the most relevant side effects. Although the negative impact of corticosteroid treatment on growth rate remained their major concern, parents and patients stated that they preferred corticosteroid therapy.

Long-term corticosteroid treatment is effective in prolonging function but not in recovering lost function, and its early use seems appropriate.

    Corticosteroid treatment
    MEDICATION

 is the standard of care in

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, but the optimal

    age to initiate treatment
    MEDICATION

 and dosage pattern remain a matter of discussion.

We performed a

    long-term study of alternate-day corticosteroids
    MEDICATION

 in five

    2- to 4-year-old
    AGE

    DMD
    DIAGNOSIS

 patients. The primary outcome measure was

    prolongation of the ability to walk
    SYMPTOMS

.

One patient

    lost ambulation
    SYMPTOMS

 at

    age 10
    AGE

. Four patients,

    aged 16 to 18
    AGE

 were

    fully ambulant
    SYMPTOMS

, and 3 of them

    could still climb stairs
    NEG_FINDINGS

.

    Respiratory function was moderately reduced
    SYMPTOMS

 in 2.

    Left ventricular ejection fraction was > 45%
    SYMPTOMS

.

    Short stature
    SYMPTOMS

 and

    delayed puberty
    SYMPTOMS

 were the most relevant side effects. Although the

    negative impact of corticosteroid treatment
    SYMPTOMS

    on growth rate
    SYMPTOMS

 remained their major concern, parents and patients stated that they preferred

    corticosteroid therapy
    MEDICATION

.

    Long-term corticosteroid treatment
    MEDICATION

 is effective in

    prolonging function
    SYMPTOMS

 but

    not in recovering lost function
    NEG_FINDINGS

, and its early use seems appropriate.

could still climb stairs
not in recovering lost function


Duchenne muscular dystrophy in a 4-year-old girl due to heterozygous frame shift deletion of the dystrophin gene and skewed X-inactivation.

X-linked recessive diseases affect males, whereas female carriers are generally asymptomatic.We report on a 4-year-old girl who presented with a classical phenotype of Duchenne Muscular Dystrophy (DMD), a severe X-linked recessive type of muscular dystrophy affecting boys in early childhood.A thorough diagnostic work-up revealed that this resulted from a heterozygous out-of frame deletion in the DMD-gene in combination with an X-inactivation ratio of <10:90 in blood leukocytes and muscle.The case exemplifies that a skewed X-inactivation pattern has to be taken into account as mechanism causing clinical symptoms in female carriers of X-linked recessive disorders.

    X-linked recessive diseases
    GENETICS

 affect

    males
    GENDER

, whereas

    female
    GENDER

 carriers are generally

    asymptomatic
    NEG_FINDINGS

.We report on a

    4-year-old
    AGE

    girl
    GENDER

 who presented with a classical phenotype of

    Duchenne Muscular Dystrophy (DMD)
    DIAGNOSIS

, a

    severe X-linked recessive type of muscular dystrophy
    DIAGNOSIS

 affecting

    boys
    GENDER

    in early childhood
    AGE

.A thorough

    diagnostic work-up
    PARACLINICAL

 revealed that this resulted from a

    heterozygous out-of frame deletion in the DMD-gene in combination with an X-inactivation ratio of <10:90 in blood leukocytes and muscle
    GENETICS

.The case exemplifies that a

    skewed X-inactivation pattern
    GENETICS

 has to be taken into account as mechanism causing

    clinical symptoms
    SYMPTOMS

 in

    female
    GENDER

 carriers of

    X-linked recessive disorders
    GENETICS

.


Variations of left atrial activation patterns in congestive heart failure.

We report about a case of a patient admitted to the Intensive Cardiac Care Unit for severe congestive heart failure which showed modification of P-wave morphology and duration, correlated with the clinical evolution. In the case here described, we show that ECG analysis, specifically P wave, allow us to assess the hemodynamic evolution of the acute decompensated heart failure patient. Electrocardiographic examination is the first and the most simple and available diagnostic tool in the evaluation of patients with cardiac diseases. Usually, P-wave evaluation is not carefully assessed, in spite of very useful informations we can draw from its interpretation. We report about a patient admitted to our Intensive Cardiac Care Unit (ICCU) for severe congestive heart failure which showed peculiar modification of P-wave morphology and duration, well correlated with the clinical course.

We report about a case of a patient admitted to the

    Intensive Cardiac Care Unit
    MEDICATION

 for

    severe congestive heart failure
    DIAGNOSIS

 which showed

    modification of P-wave morphology and duration
    SYMPTOMS

, correlated with the clinical evolution. In the case here described, we show that

    ECG analysis
    PARACLINICAL

, specifically P wave, allow us to assess the hemodynamic evolution of the

    acute decompensated heart failure
    DIAGNOSIS

 patient.

    Electrocardiographic examination
    PARACLINICAL

 is the first and the most simple and available diagnostic tool in the evaluation of patients with

    cardiac diseases
    DIAGNOSIS

. Usually,

    P-wave evaluation
    PARACLINICAL

 is not carefully assessed, in spite of very useful informations we can draw from its interpretation. We report about a patient admitted to our

    Intensive Cardiac Care Unit (ICCU)
    MEDICATION

 for

    severe congestive heart failure
    DIAGNOSIS

 which showed

    peculiar modification of P-wave morphology and duration
    SYMPTOMS

, well correlated with the clinical course.

Intensive Cardiac Care Unit
Intensive Cardiac Care Unit (ICCU)

severe congestive heart failure
acute decompensated heart failure
cardiac diseases
severe congestive heart failure


Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes protein misfolding and mild Becker muscular dystrophy.

Mutations in the dystrophin gene without disruption of the reading frame often lead to Becker muscular dystrophy, but a genotype/phenotype correlation is difficult to establish. Amino acid substitutions may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two brothers (ages 8 and 10 years) with very mild proximal weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin gene (c.1280T>C) leading to a L427P amino acid substitution in repeat 1 of the central rod domain. Immunostaining of skeletal muscle showed weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial misfolding of the L427P mutated protein as well as a reduced refolding rate after denaturation. Based on computational homology models of the wild-type and mutated R1-2, a molecular dynamics study showed an alteration in the flexibility of the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this missense mutation hinders the dynamic properties of the entire N-terminal region of dystrophin.

    Mutations in the dystrophin gene
    GENETICS

    without disruption of the reading frame
    NEG_FINDINGS

 often lead to

    Becker muscular dystrophy
    DIAGNOSIS

, but a genotype/phenotype correlation is difficult to establish.

    Amino acid substitutions
    GENETICS

 may disrupt binding capacities of dystrophin and have a major impact on the functionality of this protein. We have identified two

    brothers
    GENDER

 (

    ages 8 and 10 years
    AGE

) with

    very mild proximal weakness
    SYMPTOMS

,

    recurrent abdominal pain
    SYMPTOMS

, and

    moderately elevated serum creatine kinase levels
    BIOCHEMICAL

.

    Gene sequencing
    PARACLINICAL

 revealed a

    novel mutation in exon 11 of the dystrophin gene (c.1280T>C) leading to a L427P amino acid substitution in repeat 1 of the central rod domain
    GENETICS

.

    Immunostaining of skeletal muscle
    PARACLINICAL

 showed

    weak staining of the dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin-binding domain 1 and the N-terminal part of hinge 1
    SYMPTOMS

.

    Spectrofluorescence and circular dichroism analysis of the domain repeat 1-2 (R1-2)
    PARACLINICAL

 revealed

    partial misfolding of the L427P mutated protein
    GENETICS

 as well as a

    reduced refolding rate after denaturation
    BIOCHEMICAL

. Based on

    computational homology models of the wild-type and mutated R1-2
    PARACLINICAL

, a

    molecular dynamics study
    PARACLINICAL

 showed an

    alteration in the flexibility of
    SYMPTOMS

 the structure, which also strongly affects the conformational space available in the N-terminal region of the fragment. Our results suggest that this

    missense mutation
    GENETICS

 hinders the dynamic properties of the entire N-terminal region of dystrophin.


Detection of truncated dystrophin lacking the C-terminal domain in a Chinese pedigree by next-generation sequencing.

Dystrophin (DMD) gene is the largest gene containing 79 exons involving various mutation types and regions, and targeted next-generation sequencing (NGS) was employed in detecting DMD gene mutation in the present study. A literature-annotated disease nonsense mutation (c.10141C>T, NM_004006.1) in exon 70 that has been reported as Duchenne Muscular Dystrophy (DMD)-causing mutation was found in our two patients, the proband and his cousin. In the present study two main methods were used, the next-generation sequencing and the classic Sanger sequencing. The exon capture followed by HiSeq2000 sequencing was specifically used in this study. Combined applications of the next-generation sequencing platform and bioinformatics are proved to be effective methods for DMD diagnosis.

    Dystrophin (DMD) gene
    GENETICS

 is the

    largest gene containing 79 exons
    GENETICS

 involving various mutation types and regions, and

    targeted next-generation sequencing (NGS)
    PARACLINICAL

 was employed in detecting

    DMD gene mutation
    GENETICS

 in the present study. A

    literature-annotated disease nonsense mutation (c.10141C>T, NM_004006.1) in exon 70 that has
    GENETICS

 been reported as

    Duchenne Muscular Dystrophy (DMD)-causing mutation
    DIAGNOSIS

 was found in our two patients, the

    proband and his cousin
    FAMILY

. In the present study two main methods were used, the

    next-generation sequencing
    PARACLINICAL

 and the

    classic Sanger sequencing
    PARACLINICAL

. The

    exon capture followed by HiSeq2000 sequencing
    PARACLINICAL

 was specifically used in this study. Combined applications of the next-generation sequencing platform and bioinformatics are proved to be effective methods for

    DMD
    DIAGNOSIS

 diagnosis.


[Recurrent gastric volvulus resolved surgically after therapeutic percutaneous endoscopic gastrostomy in Duchenne muscular dystrophy].

A 20-year-old man with Duchenne muscular dystrophy (DMD) with recurrent gastric volvulus underwent percutaneous endoscopic gastrostomy (PEG). Four months later, he developed vomiting and consciousness disturbance. CT revealed gastric volvulus recurrence along the gastrostomy axis. Endoscopic repositioning failed and fistula perforation necessitated emergency surgery. The upper position of the stomach was twisted counter-clockwise and revolved on the gastrostomy axis sliding between the lower stomach and abdominal wall. The fistula showed necrotic perforation and was thus resected. The anterior stomach wall was fixed to the abdominal wall at 3 triangular points. Thereafter, gastric volvulus did not recur. PEG is reportedly effective for preventing gastric volvulus, but there are rare cases of postgastrostomy recurrence. This successfully managed case provides valuable clinical insights.

A

    20-year-old
    AGE

    man
    GENDER

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 with

    recurrent gastric volvulus
    SYMPTOMS

 underwent

    percutaneous endoscopic gastrostomy (PEG)
    MEDICATION

. Four months later,

    he
    GENDER

 developed

    vomiting
    SYMPTOMS

 and

    consciousness disturbance
    SYMPTOMS

.

    CT
    PARACLINICAL

 revealed

    gastric volvulus recurrence along the gastrostomy axis
    SYMPTOMS

.

    Endoscopic repositioning failed
    NEG_FINDINGS

 and

    fistula perforation
    SYMPTOMS

 necessitated

    emergency surgery
    MEDICATION

. The

    upper position of the stomach was twisted counter-clockwise and revolved on the gastrostomy axis sliding between the lower stomach and abdominal wall
    SYMPTOMS

. The

    fistula showed necrotic perforation
    SYMPTOMS

 and was thus

    resected
    MEDICATION

.

    The anterior stomach wall was fixed to the abdominal wall at 3 triangular points
    MEDICATION

. Thereafter,

    gastric volvulus did not recur
    NEG_FINDINGS

.

    PEG
    MEDICATION

 is reportedly effective for

    preventing gastric volvulus
    SYMPTOMS

, but there are rare cases of

    postgastrostomy recurrence
    SYMPTOMS

. This successfully managed case provides valuable clinical insights.

Endoscopic repositioning failed
gastric volvulus did not recur


[Legal liability problems in outpatient operations. View from an anesthesiological perspective].

The rapid technical and medical progress in endoscopic and laparoscopic interventions and the increasing acceptance by patients, lead to an expansion of outpatient operations. The endoscopic laparoscopic operation technique, the operative implementation and the inclusion of an accompanying and a surveillance person in the postoperative phase conceal, however, specific dangers which the physician must recognize and remove. It is absolutely necessary that anesthetists pay attention to some basic principles concerning protection and safety of patients, considerations on the comfort of patients, quality measures and the resulting practical consequences. Particularly prone to liability problems are the postoperative phase and discharge of patients which will be demonstrated in some exemplary cases.

The rapid technical and medical progress in

    endoscopic and laparoscopic interventions
    MEDICATION

 and the increasing acceptance by patients, lead to an expansion of

    outpatient operations
    MEDICATION

. The

    endoscopic laparoscopic operation technique
    MEDICATION

, the

    operative implementation
    MEDICATION

 and the inclusion of an accompanying and a surveillance person in the postoperative phase conceal, however, specific dangers which the physician must recognize and remove. It is absolutely necessary that

    anesthetists
    PARACLINICAL

 pay attention to some basic principles concerning protection and safety of patients, considerations on the comfort of patients, quality measures and the resulting practical consequences. Particularly prone to liability problems are the postoperative phase and discharge of patients which will be demonstrated in some exemplary cases.


Unusual respiratory manifestations in two young adults with Duchenne muscular dystrophy.

Adult respirologists are often involved in the evaluation and treatment of young adult patients with Duchenne muscular dystrophy. In this context, the most frequent respiratory complication is nocturnal and daytime hypoventilation related to respiratory muscle weakness. The present article describes cases of Duchenne muscular dystrophy involving two brothers, 17 and 19 years of age, respectively, who presented with less frequently reported respiratory complications of their disease: obstructive sleep apnea and Cheyne-Stokes respiration with central apnea, which were believed to be partially or completely related to congestive cardiomyopathy.

    Adult respirologists
    PARACLINICAL

 are often involved in the evaluation and treatment of

    young adult
    AGE

 patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

. In this context, the most frequent

    respiratory complication
    SYMPTOMS

 is

    nocturnal and daytime hypoventilation
    SYMPTOMS

 related to

    respiratory muscle weakness
    SYMPTOMS

. The present article describes cases of

    Duchenne muscular dystrophy
    DIAGNOSIS

 involving two

    brothers
    GENDER

,

    17 and 19 years of age
    AGE

, respectively, who presented with less frequently reported

    respiratory complications
    SYMPTOMS

 of their disease:

    obstructive sleep apnea
    SYMPTOMS

 and

    Cheyne-Stokes respiration with central apnea
    SYMPTOMS

, which were believed to be partially or completely related to

    congestive cardiomyopathy
    SYMPTOMS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy


A neonate with contiguous deletion syndrome in XP21.

We report a case of a male infant with the association of pseudohypertriglyceridemia, hypoadrenalism (hyponatremia, hyperpotasemia, dehydration), high creatine phosphokinase level (possible Duchenne's muscular dystrophy, DMD) and diagnosed contiguous gene deletion syndrome in Xp21.

A 1-month-old male term infant was referred due to no weight gain. The examination revealed dehydration (decreased skin turgor), scrotal hyperpigmentation and hypotonia. Laboratory findings showed hyponatremia of 124 mmol/L, hyperpotasemia of 6.9 mg/dL, high creatine phosphokinase level of 7019 IU/L, and high blood triglyceride level of 1244 mg/dL. There was no deletion detected in the dystrophin gene with the study investigating selected exons, no dystrophin staining and nonspecific atrophic findings in the muscle biopsy. Further laboratory findings defined high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency (GKD). Array CGH study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, GKD and the congenital adrenal hypoplasia (gene DAX1 or NROB1 gene: Xp21.3-21.2). The infant showed good response to mineralocorticoid therapy, hyponatremia resolved and gained weight.

Physicians should consider contiguous gene deletion syndrome in Xp21 in the infants with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia to be able to prevent and treat the metabolic complications. Furthermore, geneticists should take into account to design routine deletion studies including the promoter region in this disorder.

We report a case of a

    male
    AGE

    infant
    AGE

 with the association of

    pseudohypertriglyceridemia
    BIOCHEMICAL

,

    hypoadrenalism (hyponatremia, hyperpotasemia, dehydration)
    BIOCHEMICAL

,

    high creatine phosphokinase level
    BIOCHEMICAL

 (

    possible Duchenne's muscular dystrophy, DMD)
    DIAGNOSIS

 and diagnosed

    contiguous gene deletion syndrome in Xp21.
    GENETICS

A

    1-month-old
    AGE

    male
    GENDER

    term infant
    AGE

 was referred due to

    no weight gain
    NEG_FINDINGS

. The examination revealed

    dehydration (decreased skin turgor)
    SYMPTOMS

,

    scrotal hyperpigmentation
    SYMPTOMS

 and

    hypotonia
    SYMPTOMS

.

    Laboratory findings
    PARACLINICAL

 showed

    hyponatremia of 124 mmol/L
    BIOCHEMICAL

,

    hyperpotasemia of 6.9 mg/dL
    BIOCHEMICAL

,

    high creatine phosphokinase level of 7019 IU/L
    BIOCHEMICAL

, and high blood triglyceride level of 1244 mg/dL. There was

    no deletion detected in the dystrophin gene with the study investigating selected exons
    NEG_FINDINGS

,

    no dystrophin staining
    NEG_FINDINGS

 and

    nonspecific atrophic findings in the muscle biopsy
    NEG_FINDINGS

. Further laboratory findings defined

    high glycerol concentrations both in blood and in urine
    BIOCHEMICAL

 that were compatible with a

    glycerol kinase deficiency (GKD)
    BIOCHEMICAL

.

    Array CGH study
    PARACLINICAL

 confirmed the

    existence of a deletion in Xp21 of the genes responsible for DMD
    GENETICS

,

    GKD
    DIAGNOSIS

 and the

    congenital adrenal hypoplasia
    DIAGNOSIS

    (gene DAX1 or NROB1 gene: Xp21.3-21.2)
    GENETICS

. The

    infant
    AGE

 showed good response to

    mineralocorticoid therapy
    MEDICATION

,

    hyponatremia resolved
    BIOCHEMICAL

 and

    gained weight
    SYMPTOMS

.

Physicians should consider

    contiguous gene deletion syndrome in Xp21
    GENETICS

 in the

    infants
    AGE

 with

    myopathic compromise
    SYMPTOMS

,

    increased levels of creatine phosphokinase
    BIOCHEMICAL

 and

    pseudohypertriglyceridaemia
    BIOCHEMICAL

 to be able to prevent and treat the

    metabolic complications
    SYMPTOMS

. Furthermore,

    geneticists
    PARACLINICAL

 should take into account to design

    routine deletion studies including the promoter region
    PARACLINICAL

 in this disorder.

dehydration (decreased skin turgor)
scrotal hyperpigmentation
hypotonia
gained weight
myopathic compromise
metabolic complications


The first case of primary alpha-sarcoglycanopathy identified in Albania, in two siblings with homozygous alpha-sarcoglycan mutation.

Limb-girdle muscular dystrophy type 2D (LGMD2D) is caused by autosomal recessive mutations in the alpha-sarcoglycan gene. The clinical, biochemical, histological, imunohistochemical and molecular genetic data in 2 Albanian siblings with LGMD2D (adhalinopathy or alpha-sarcoglycanopathy) are presented and the resemblance with Duchenne muscular dystrophy (DMD) is discussed. Both siblings had very high level of CK and a negative molecular test for DMD deletions and duplications. The muscle biopsy showed dystrophic features as well as deficiency in two different proteins, the Gamma sarcoglycan protein (-SG) and the Alpha -SG protein (-SG). DNA analysis demonstrated homozygosity for a pathogenic point mutation (574C>T) in the alpha-sarcoglycan gene, confirming the diagnosis of limb-girdle muscular dystrophy type 2D. We believe it is the first confirmed case of primary alpha-sarcoglycanopathy identified in Albania which support the assumption of a wide geographic prevalence of severe childhood onset of autosomal recessive muscular dystrophy, We show that muscle biopsy and DNA diagnosis remains the most sensitive and specific method for differential diagnosis.

    Limb-girdle muscular dystrophy type 2D (LGMD2D)
    DIAGNOSIS

 is caused by

    autosomal recessive mutations in the alpha-sarcoglycan gene
    GENETICS

. The clinical,

    biochemical, histological, imunohistochemical and molecular genetic
    PARACLINICAL

 data in 2

    Albanian
    ETHNICITY

 siblings with

    LGMD2D (adhalinopathy or alpha-sarcoglycanopathy)
    DIAGNOSIS

 are presented and the resemblance with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is discussed.

    Both siblings had very high level of CK
    FAMILY

 and a

    negative molecular test for DMD deletions and duplications
    NEG_FINDINGS

. The

    muscle biopsy
    PARACLINICAL

 showed

    dystrophic features
    SYMPTOMS

 as well as

    deficiency in two different proteins, the Gamma sarcoglycan protein (-SG) and the Alpha -SG protein (-SG)
    BIOCHEMICAL

.

    DNA analysis
    PARACLINICAL

 demonstrated

    homozygosity for a pathogenic point mutation (574C>T) in the alpha-sarcoglycan gene
    GENETICS

, confirming the diagnosis of limb-girdle muscular dystrophy type 2D. We believe it is the first confirmed case of

    primary alpha-sarcoglycanopathy
    DIAGNOSIS

 identified in

    Albania
    ETHNICITY

 which support the assumption of a wide geographic prevalence of

    severe childhood onset
    DIAGNOSIS

 of

    autosomal recessive muscular dystrophy
    DIAGNOSIS

, We show that

    muscle biopsy
    PARACLINICAL

 and

    DNA diagnosis
    PARACLINICAL

 remains the most sensitive and specific method for

    differential diagnosis
    PARACLINICAL

.


[Sugammadex, efficacious in reversing a neuromuscular block in a woman with Becker muscular dystrophy].

Becker muscular dystrophy affects mainly the musculoskeletal system, causing muscle wasting and progressive weakness. A 61-year-old woman with breast cancer, who had been diagnosed with Becker muscular dystrophy 45 years earlier, was scheduled for right mastectomy. We induced general anesthesia with propofol, fentanyl, and a nondepolarizing muscle blocker (rocuronium). Neuromuscular function was monitored continuously by acceleromyographic train-of-four ratio (TOFr) (Watch-SX monitor). The block was reversed with sugammadex. After preoxygenation with fentanyl and propofol, the device was calibrated and the baseline TOFr was recorded. We injected 1 mg/kg of rocuronium and assessed TOF responses every 15 seconds. The maximum decrease in TOF response (to 0 twitches) was at 52 seconds. Tracheal intubation was uneventful. Anesthesia was maintained by intravenous infusion. The operation lasted 74 minutes. The second TOF twitch (T2) reappeared 86 minutes after the initial dose. After we injected 2 mg/kg of sugammadex, a TOFr of 0.7 was reached at 79 seconds; a TOFr of 0.9 was reached at 108 seconds and a TOFr of 1.0 at 152 seconds. No electrocardiographic or hemodynamic abnormalities occurred during sugammadex administration and there were no signs of residual neuromuscular blockade on awakening or adverse events in the following 24 hours.

    Becker muscular dystrophy
    DIAGNOSIS

 affects mainly

    the musculoskeletal system
    SYMPTOMS

, causing

    muscle wasting
    SYMPTOMS

 and

    progressive weakness
    SYMPTOMS

. A

    61-year-old
    AGE

    woman
    GENDER

 with

    breast cancer
    DIAGNOSIS

, who had been diagnosed with

    Becker muscular dystrophy
    DIAGNOSIS

 45 years earlier, was scheduled for

    right mastectomy
    MEDICATION

. We

    induced general anesthesia with propofol, fentanyl, and a nondepolarizing muscle blocker (rocuronium)
    MEDICATION

.

    Neuromuscular function
    PARACLINICAL

 was monitored continuously by

    acceleromyographic train-of-four ratio (TOFr) (Watch-SX monitor)
    PARACLINICAL

. The block was

    reversed with sugammadex
    MEDICATION

. After

    preoxygenation with fentanyl and propofol
    MEDICATION

, the device was calibrated and the

    baseline TOFr was recorded
    PARACLINICAL

. We

    injected 1 mg/kg of rocuronium
    MEDICATION

 and

    assessed TOF responses every 15 seconds
    PARACLINICAL

. The

    maximum decrease in TOF response (to 0 twitches) was at 52 seconds
    SYMPTOMS

.

    Tracheal intubation
    MEDICATION

 was

    uneventful
    NEG_FINDINGS

.

    Anesthesia
    MEDICATION

 was

    maintained by intravenous infusion
    MEDICATION

. The

    operation lasted 74 minutes
    MEDICATION

. The

    second TOF twitch (T2) reappeared
    SYMPTOMS

 86 minutes after the initial dose. After we

    injected 2 mg/kg of sugammadex
    MEDICATION

, a

    TOFr of 0.7 was reached at 79 seconds
    SYMPTOMS

; a

    TOFr of 0.9 was reached
    SYMPTOMS

 at 108 seconds and a

    TOFr of 1.0 at 152 seconds
    SYMPTOMS

.

    No electrocardiographic or hemodynamic abnormalities
    NEG_FINDINGS

 occurred during

    sugammadex administration
    MEDICATION

 and there were

    no signs of residual neuromuscular blockade on awakening or adverse events in the following 24 hours
    NEG_FINDINGS

.

Becker muscular dystrophy
breast cancer
Becker muscular dystrophy


Physical training in Becker muscular dystrophy associated with heart failure.

Becker muscular dystrophy (BMD) integrates dystrophy occurring due to genetic mutations that express the dystrophin protein in chromosome X. The onset of neuromuscular symptoms usually precedes the impairment of cardiac function, and may conversely happen by heart failure (HF). Physical training is well established in HF, however, when combined with BMD, it is controversial and without any scientific basis. This study presents the case of a patient with BMD associated with HF in cardiac transplant waiting list undergoing a physical training program.

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 integrates

    dystrophy
    DIAGNOSIS

 occurring due to genetic mutations that express the dystrophin protein in chromosome X. The onset of

    neuromuscular symptoms
    SYMPTOMS

 usually precedes the

    impairment of cardiac function
    SYMPTOMS

, and may conversely happen by

    heart failure (HF)
    DIAGNOSIS

.

    Physical training
    MEDICATION

 is well established in

    HF
    DIAGNOSIS

, however, when combined with

    BMD
    DIAGNOSIS

, it is controversial and without any scientific basis. This study presents the case of a patient with

    BMD associated with HF
    DIAGNOSIS

 in

    cardiac transplant waiting list
    MEDICATION

 undergoing a

    physical training program
    MEDICATION

.

Becker muscular dystrophy (BMD)
dystrophy
heart failure (HF)
HF
BMD
BMD associated with HF

neuromuscular symptoms
impairment of cardiac function

Physical training
cardiac transplant waiting list
physical training program


Case presentation: abdominal compartment syndrome complicating posterior spinal fusion.

Abdominal compartment syndrome (ACS) is a life-threatening entity that requires rapid recognition and treatment. This case report represents the first case report of ACS associated with the correction of a marked scoliosis. Of the many possible causes for respiratory compromise and cardiovascular collapse associated with major spine surgery, ACS should be considered, particularly in instances of profound spinal curvature correction. We present the case of an 8-year-old child with Duchenne muscular dystrophy (DMD) undergoing correction of a severe scoliotic curvature. Near the end of an otherwise unremarkable surgery, he developed severe respiratory compromise associated with respiratory acidosis, hypoxia, and hypotension in the face of a catastrophic decrease in lung compliance. After supine positioning and examination, he was discovered to have ACS, which was treated with laparotomy. Complete recovery occurred after 5 days. This case report should raise awareness of a rare, life threatening, but imminently treatable entity that can accompany scoliosis surgery. The description of this case should be particularly important for pediatric anesthesiologists and orthopedic surgeons who care for patients undergoing correction of marked scoliosis. We suggest possible mechanisms for the development of ACS in this setting that offer insights into the pathology of this entity, which could be useful in many other clinical situations where visceral venous drainage or bowel perfusion may be compromised.

    Abdominal compartment syndrome (ACS)
    DIAGNOSIS

 is a life-threatening entity that requires rapid recognition and treatment. This case report represents the first case report of

    ACS
    DIAGNOSIS

 associated with the

    correction of a marked scoliosis
    MEDICATION

. Of the many possible causes for

    respiratory compromise
    SYMPTOMS

 and

    cardiovascular collapse
    SYMPTOMS

 associated with

    major spine surgery
    MEDICATION

,

    ACS
    DIAGNOSIS

 should be considered, particularly in instances of

    profound spinal curvature correction
    MEDICATION

. We present the case of an

    8-year-old
    AGE

    child
    AGE

 with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 undergoing

    correction of a severe scoliotic curvature
    MEDICATION

. Near the end of an

    otherwise unremarkable surgery
    NEG_FINDINGS

,

    he
    GENDER

 developed

    severe respiratory compromise
    SYMPTOMS

 associated with

    respiratory acidosis
    SYMPTOMS

,

    hypoxia
    SYMPTOMS

, and

    hypotension
    SYMPTOMS

 in the face of a

    catastrophic decrease in lung compliance
    SYMPTOMS

. After

    supine positioning
    MEDICATION

 and examination,

    he
    GENDER

 was discovered to have

    ACS
    DIAGNOSIS

, which was treated with

    laparotomy
    MEDICATION

.

    Complete recovery
    SYMPTOMS

 occurred after 5 days. This case report should raise awareness of a rare,

    life threatening
    SYMPTOMS

, but imminently treatable entity that can accompany

    scoliosis surgery
    MEDICATION

. The description of this case should be particularly important for

    pediatric anesthesiologists
    PARACLINICAL

 and

    orthopedic surgeons
    MEDICATION

 who care for patients undergoing

    correction of marked scoliosis
    MEDICATION

. We suggest possible mechanisms for the development of

    ACS
    DIAGNOSIS

 in this setting that offer insights into the pathology of this entity, which could be useful in many other clinical situations where

    visceral venous drainage or bowel perfusion may be compromised
    SYMPTOMS

.

Abdominal compartment syndrome (ACS)
ACS
ACS
Duchenne muscular dystrophy (DMD)
ACS
ACS


Idiopathic intracranial hypertension in a child with Duchenne muscular dystrophy.

Duchenne muscular dystrophy is an X-linked, recessively inherited disorder characterized by progressive weakness attributable to the absence of dystrophin expression in muscle. In multiple studies, the chronic administration of corticosteroids slowed the loss of ambulation that develops in mid to late childhood. Corticosteroids, however, frequently produce unacceptable side effects, including Cushingoid appearance and weight gain. Deflazacort, an oxazoline analogue of prednisolone, produces equivalent benefits on muscle with fewer reported Cushingoid side effects. We present a 9-year-old boy with Duchenne muscular dystrophy who developed morbid obesity and subsequent idiopathic intracranial hypertension after 2 years of receiving deflazacort. Although deflazacort is typically thought to produce less obesity than prednisone, severe Cushingoid side effects may occur in some individuals. To our knowledge, this description is the first of idiopathic intracranial hypertension complicating chronic corticosteroid treatment of Duchenne muscular dystrophy.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is an

    X-linked, recessively inherited
    GENETICS

 disorder characterized by

    progressive weakness
    SYMPTOMS

 attributable to the

    absence of dystrophin expression in muscle
    SYMPTOMS

. In multiple studies, the

    chronic administration of corticosteroids
    MEDICATION

 slowed the

    loss of ambulation
    SYMPTOMS

 that develops in

    mid to late childhood
    AGE

.

    Corticosteroids
    MEDICATION

, however, frequently produce

    unacceptable side effects
    SYMPTOMS

, including

    Cushingoid appearance
    SYMPTOMS

 and

    weight gain
    SYMPTOMS

.

    Deflazacort, an oxazoline analogue of prednisolone
    MEDICATION

, produces

    equivalent benefits on muscle
    SYMPTOMS

 with

    fewer reported Cushingoid side effects
    SYMPTOMS

. We present a

    9-year-old
    AGE

    boy
    GENDER

 with

    Duchenne muscular dystrophy
    DIAGNOSIS

 who developed

    morbid obesity
    SYMPTOMS

 and subsequent

    idiopathic intracranial hypertension
    SYMPTOMS

 after

    2 years of receiving deflazacort
    MEDICATION

. Although

    deflazacort
    MEDICATION

 is typically thought to produce

    less obesity
    SYMPTOMS

 than

    prednisone
    MEDICATION

,

    severe Cushingoid side effects
    SYMPTOMS

 may occur in some individuals. To our knowledge, this description is the first of

    idiopathic intracranial hypertension
    SYMPTOMS

 complicating

    chronic corticosteroid treatment
    MEDICATION

 of

    Duchenne muscular dystrophy
    DIAGNOSIS

.

Duchenne muscular dystrophy
Duchenne muscular dystrophy
Duchenne muscular dystrophy


Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon.

Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic "copy and paste" mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, noncoding RNA transcribed from chromosome 11q22.3 that retrotransposed into the dystrophin gene. Here, we demonstrate that a nonreference full-length LINE-1 is situated in the proband and maternal genome at chromosome 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3' transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1-mediated 3' transduction with severe 5' truncation. This is the first example of LINE-1-induced human disease caused by an "orphan" 3' transduction.

    Long INterspersed Element-1 (LINE-1) retrotransposons
    MICROSCOPIC

 comprise 17% of the human genome, and move by a potentially mutagenic "copy and paste" mechanism via an

    RNA intermediate
    GENETICS

. Recently, the

    retrotransposition-mediated insertion of a new transcript
    MICROSCOPIC

 was described as a novel cause of

    genetic disease
    DIAGNOSIS

,

    Duchenne muscular dystrophy
    DIAGNOSIS

, in a

    Japanese
    ETHNICITY

    male
    GENDER

. The inserted sequence was presumed to derive from a

    single-copy, noncoding RNA transcribed from chromosome 11q22.3 that retrotransposed into the dystrophin gene
    GENETICS

. Here, we demonstrate that a

    nonreference full-length LINE-1 is situated in the proband and maternal genome at chromosome 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene
    GENETICS

. This

    LINE-1
    MICROSCOPIC

 is highly active in a

    cell culture assay
    PARACLINICAL

.

    LINE-1 insertions
    MICROSCOPIC

 are often associated with

    3' transduction of adjacent genomic sequences
    GENETICS

. Thus, the likely explanation for the mutagenic insertion is a

    LINE-1-mediated 3' transduction with severe 5' truncation
    GENETICS

. This is the first example of

    LINE-1-induced human disease
    DIAGNOSIS

 caused by an "

    orphan" 3' transduction
    GENETICS

.

genetic disease
Duchenne muscular dystrophy
LINE-1-induced human disease


Childhood onset of left ventricular dysfunction in a female manifesting carrier of muscular dystrophy.

Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked disorders that result from a mutation in the dystrophin gene that reduces the production or effectiveness of the protein dystrophin. These disorders are clinically characterized by progressive muscle degeneration. Manifesting female carriers are generally not identified as such until after puberty, when symptoms such as muscle weakness may arise. This clinical report describes a female manifesting carrier who started to show deterioration of left ventricular systolic function, but no marked skeletal muscle weakness, at the age of 10 years. The patient's cardiac function improved significantly after dual drug therapy with an ACE inhibitor (enalapril) and a beta-blocker (carvedilol). Our case adds to the existing evidence that left ventricular myocardial dysfunction may occur during childhood in female carriers of dystrophinopathies.

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    Becker muscular dystrophy
    DIAGNOSIS

 are

    X-linked disorders
    GENETICS

 that result from a

    mutation in the dystrophin gene
    GENETICS

 that

    reduces the production or effectiveness of the protein dystrophin
    BIOCHEMICAL

. These disorders are clinically characterized by

    progressive muscle degeneration
    SYMPTOMS

. Manifesting

    female
    GENDER

 carriers are generally not identified as such until

    after puberty
    AGE

, when symptoms such as

    muscle weakness
    SYMPTOMS

 may arise. This clinical report describes a

    female
    GENDER

 manifesting carrier who started to show

    deterioration of left ventricular systolic function
    SYMPTOMS

, but

    no marked skeletal muscle weakness
    NEG_FINDINGS

, at the

    age of 10 years
    AGE

. The patient's

    cardiac function
    SYMPTOMS

 improved significantly after

    dual drug therapy with an ACE inhibitor (enalapril) and a beta-blocker (carvedilol)
    MEDICATION

. Our case adds to the existing evidence that

    left ventricular myocardial dysfunction
    SYMPTOMS

 may occur during

    childhood
    AGE

 in

    female
    GENDER

 carriers of

    dystrophinopathies
    DIAGNOSIS

.

Duchenne muscular dystrophy
Becker muscular dystrophy
dystrophinopathies

X-linked disorders
mutation in the dystrophin gene


Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene.

The use of hybridization-based methods for Duchenne muscular dystrophy (DMD) mutation analysis is increasingly common. We report a case of Becker muscular dystrophy in which discrepant results between a polymerase chain reaction (PCR)-based single-condition amplification/internal primer (SCAIP) and a comparative genomic hybridization assay incompletely characterized the mutation (an inversion of exons 23 and 24). These results demonstrate the limits of sensitivity and specificity of both tests, and highlight the need for more detailed analysis when intronic deletions are detected by comparative genome hybridization methods.

The use of

    hybridization-based methods
    PARACLINICAL

 for

    Duchenne muscular dystrophy (DMD) mutation analysis
    DIAGNOSIS

 is increasingly common. We report a case of

    Becker muscular dystrophy
    DIAGNOSIS

 in which discrepant results between a

    polymerase chain reaction (PCR)-based single-condition amplification/internal primer (SCAIP)
    PARACLINICAL

 and a

    comparative genomic hybridization assay
    PARACLINICAL

 incompletely

    characterized the mutation (an inversion of exons 23 and 24)
    GENETICS

. These results demonstrate the limits of sensitivity and specificity of both tests, and highlight the need for more detailed analysis when

    intronic deletions
    GENETICS

 are detected by

    comparative genome hybridization methods
    PARACLINICAL

.


How should we monitor pediatric patients with Duchenne muscular dystrophy? -A case report-.

Duchenne muscular dystrophy is a hereditary disorder characterized by progressive muscle weakness and contracture, and special care during anesthesia is needed in these patients. Because inhalational anesthetics and succinylcholine can cause fatal results, intravenous anesthetics are commonly used. However, monitorings for the pediatric population are not otherwise specified. We report our experience of a 6 year-old boy that underwent muscle biopsy suspicious of muscle dystrophy under general anesthesia. The patient received midazolam, fentanyl, propofol and a small dose of rocuronium. He was monitored with bispectral index (BIS), acceleromyography (TOF). At the end of surgery, recovery of TOF ratio to 90% was evaluated, followed by injection of pyridostigmine and glycopyrrolate. When reversal of neuromuscular block was confirmed quantitatively and clinically, the patient was extubated and he experienced no complication.

    Duchenne muscular dystrophy
    DIAGNOSIS

 is a

    hereditary disorder
    GENETICS

 characterized by

    progressive muscle weakness
    SYMPTOMS

 and

    contracture
    SYMPTOMS

, and special care during

    anesthesia
    MEDICATION

 is needed in these patients. Because

    inhalational anesthetics
    MEDICATION

 and

    succinylcholine
    MEDICATION

 can cause

    fatal results
    SYMPTOMS

,

    intravenous anesthetics
    MEDICATION

 are commonly used. However, monitorings for the

    pediatric
    AGE

 population are not otherwise specified. We report our experience of a

    6 year-old
    AGE

    boy
    GENDER

 that underwent

    muscle biopsy
    PARACLINICAL

 suspicious of

    muscle dystrophy
    DIAGNOSIS

 under

    general anesthesia
    MEDICATION

. The patient received

    midazolam, fentanyl, propofol and a small dose of rocuronium
    MEDICATION

.

    He
    GENDER

 was

    monitored with bispectral index (BIS), acceleromyography (TOF)
    PARACLINICAL

. At the end of

    surgery
    MEDICATION

,

    recovery of TOF ratio to 90%
    SYMPTOMS

 was evaluated, followed by

    injection of pyridostigmine and glycopyrrolate
    MEDICATION

. When

    reversal of neuromuscular block
    SYMPTOMS

 was confirmed quantitatively and clinically, the patient was

    extubated
    MEDICATION

 and

    he
    GENDER

 experienced

    no complication
    NEG_FINDINGS

.

Duchenne muscular dystrophy
muscle dystrophy

progressive muscle weakness
contracture
fatal results
recovery of TOF ratio to 90%
reversal of neuromuscular block


Q waves--does depth matter?

Deep narrow Q waves in an electrocardiogram may be significant and should suggest several possible diagnoses. By considering the leads where they are observed, the presence of additional ECG abnormalities, the applicant's age and any relevant clinical information, one can considerably narrow the diagnostic possibilities.

    Deep narrow Q waves in an electrocardiogram
    SYMPTOMS

 may be significant and should suggest several possible diagnoses. By considering the leads where they are observed, the presence of

    additional ECG abnormalities
    SYMPTOMS

, the applicant's age and any relevant clinical information, one can considerably narrow the diagnostic possibilities.


[Anesthetic management of a patient with Becker muscular dystrophy].

We experienced anesthetic management of a patient with Becker muscular dystrophy. He had advanced dilated cardiomyopathy and high serum CK in the preoperative examinations. Anesthesia was planned to avoid triggering malignant hyperthermia or rhabdomyolysis and hemodynamic changes. Propofol, remifentanil and a minimum dose of rocuronium bromide were used for anesthetic induction and maintainance. Arterial pressure, cardiac output and stroke volume variation were monitored by Flotrac sensor. There were no adverse events observed during the anesthetic management. In conclusion, total intravenous anesthesia with the administration of rocuronium and circulatory monitoring by Flotrac sensor could be safe and efficient for anesthetic management of patients with Becker muscular dystrophy.

We experienced

    anesthetic management
    MEDICATION

 of a patient with

    Becker muscular dystrophy
    DIAGNOSIS

.

    He
    GENDER

 had

    advanced dilated cardiomyopathy
    DIAGNOSIS

 and

    high serum CK
    BIOCHEMICAL

 in the

    preoperative examinations
    PARACLINICAL

.

    Anesthesia
    MEDICATION

 was planned to avoid

    triggering malignant hyperthermia
    NEG_FINDINGS

 or

    rhabdomyolysis
    SYMPTOMS

 and

    hemodynamic changes
    SYMPTOMS

.

    Propofol, remifentanil
    MEDICATION

 and a

    minimum dose of rocuronium bromide
    MEDICATION

 were used for

    anesthetic induction and maintainance
    MEDICATION

.

    Arterial pressure, cardiac output and stroke volume variation
    PARACLINICAL

 were

    monitored by Flotrac sensor
    PARACLINICAL

. There were

    no adverse events
    NEG_FINDINGS

 observed during the anesthetic management. In conclusion,

    total intravenous anesthesia with the administration of rocuronium
    MEDICATION

 and

    circulatory monitoring by Flotrac sensor
    PARACLINICAL

 could be safe and efficient for

    anesthetic management
    MEDICATION

 of patients with

    Becker muscular dystrophy
    DIAGNOSIS

.

Becker muscular dystrophy
advanced dilated cardiomyopathy
Becker muscular dystrophy

triggering malignant hyperthermia
no adverse events


Dexmedetomidine-ketamine sedation during bone marrow aspirate and biopsy in a patient with duchenne muscular dystrophy.

Sedation during invasive procedures not only provides appropriate humanitarian care for patients, but also facilitates the completion of invasive procedures. Although generally safe and effective, adverse effects may occur especially in patients with co-morbid diseases. We present the successful use of a combination of dexmedetomidine and ketamine to provide sedation and analgesia in a 21-year-old patient with Duchenne muscular dystrophy (DMD) undergoing bone marrow aspiration and biopsy. Co-morbidities included both depressed myocardial function and impaired respiratory function. Dexmedetomidine was administered as a loading dose of 1 μg/kg over 5 min followed by an infusion of 1 μg/kg/h. Ketamine (20 mg) was administered along with the dexmedetomidine loading dose. An additional 10 mg of ketamine was administered to treat the pain experienced during the placement of the local anesthetic agent prior to the procedure. No clinically significant hemodynamic or respiratory changes were noted. The patient tolerated the procedure well and was discharged home. A review of previously published reports of dexmedetomidine and ketamine for procedural sedation are reviewed.

    Sedation
    MEDICATION

 during

    invasive procedures
    MEDICATION

 not only provides

    appropriate humanitarian care
    MEDICATION

 for patients, but also facilitates the completion of

    invasive procedures
    MEDICATION

. Although generally safe and effective,

    adverse effects
    SYMPTOMS

 may occur especially in patients with

    co-morbid diseases
    SYMPTOMS

. We present the

    successful use of a combination of dexmedetomidine and ketamine to provide sedation and analgesia
    MEDICATION

 in a

    21-year-old
    AGE

 patient with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 undergoing

    bone marrow aspiration and biopsy
    MEDICATION

. Co-morbidities included

    both depressed myocardial function
    SYMPTOMS

 and

    impaired respiratory function
    SYMPTOMS

.

    Dexmedetomidine was administered as a loading dose of 1 μg/kg over 5 min followed by an infusion of 1 μg/kg/h. Ketamine (20 mg) was administered along with the dexmedetomidine loading dose
    MEDICATION

. An

    additional 10 mg of ketamine was administered to treat the pain experienced during the placement of the local anesthetic agent prior to the procedure
    MEDICATION

.

    No clinically significant hemodynamic or respiratory changes
    NEG_FINDINGS

 were noted. The patient tolerated the procedure well and was discharged home. A review of previously published reports of

    dexmedetomidine and ketamine for procedural sedation
    MEDICATION

 are reviewed.

adverse effects
co-morbid diseases
both depressed myocardial function
impaired respiratory function


A case of fascioscapulohumeral muscular dystrophy misdiagnosed as Becker's muscular dystrophy for 20 years.

A 60-year-old man diagnosed clinically with Becker's muscular dystrophy 20 years ago by another physician presented with gradually progressive proximal muscle weakness since teenage years. Family history revealed a strong paternal familial inheritance pattern of similar distribution of weakness-face, forearm flexion, knee extension and foot dorsiflexion. Work-ups revealed B12 deficiency and allele 1 deletion in fascioscapulohumeral muscular dystrophy (FSHD) DNA testing. FSHD is the third most common muscular dystrophy. Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing. This case strongly demonstrates the importance of a thorough and careful clinical evaluation even in a case with a long standing diagnosis.

A

    60-year-old
    AGE

    man
    GENDER

 diagnosed clinically with

    Becker's muscular dystrophy
    DIAGNOSIS

 20 years ago by another physician presented with

    gradually progressive proximal muscle weakness
    SYMPTOMS

 since

    teenage years
    AGE

.

    Family history
    FAMILY

 revealed a

    strong paternal familial inheritance pattern of similar distribution of weakness-face, forearm flexion, knee extension and foot dorsiflexion
    FAMILY

.

    Work-ups
    PARACLINICAL

 revealed

    B12 deficiency
    BIOCHEMICAL

 and

    allele 1 deletion in fascioscapulohumeral muscular dystrophy (FSHD
    GENETICS

)

    DNA testing
    PARACLINICAL

.

    FSHD
    DIAGNOSIS

 is the third most common

    muscular dystrophy
    DIAGNOSIS

. Clinical diagnosis is made from the

    distinctive pattern of weakness
    SYMPTOMS

,

    autosomal-dominant inheritance
    GENETICS

, and confirmed by

    genetic testing
    PARACLINICAL

. This case strongly demonstrates the importance of a thorough and careful clinical evaluation even in a case with a long standing diagnosis.

Becker's muscular dystrophy
FSHD
muscular dystrophy


Combination of steroids and ischial weight-bearing knee ankle foot orthoses in Duchenne's muscular dystrophy prolongs ambulation past 20 years of age--a case report.

Patients with Duchenne muscular dystrophy (DMD) lose ambulation by age 12. Long-term steroids have lengthened ambulation by 2-5 years. Ischial weight-bearing knee ankle foot orthoses prolong ambulation for 2-3 years. We report the outcome of the ambulatory status of a patient with DMD treated with daily steroid therapy and orthoses. This male patient was diagnosed with DMD at age of 2. He has been treated with daily steroids since age 7 years. He lost the ability to arise from the floor and walk up steps at age 14 and lost ambulation by age 16. He was fitted with orthoses at age 16 following surgical correction of his lower extremity contractures and regained independent ambulation. At age 20, he was able to stand independently in his orthoses and take steps with moderate support. We conclude that a combination of daily steroids and orthoses prolongs ambulation beyond that of the natural history DMD.

Patients with

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

    lose ambulation
    SYMPTOMS

 by

    age 12
    AGE

.

    Long-term steroids
    MEDICATION

 have

    lengthened ambulation
    MEDICATION

 by 2

    -5 years
    AGE

.

    Ischial weight-bearing knee ankle foot orthoses
    MEDICATION

    prolong ambulation for 2-3 years
    MEDICATION

. We report the outcome of the ambulatory status of a patient with

    DMD
    DIAGNOSIS

 treated with

    daily steroid therapy and orthoses
    MEDICATION

. This

    male
    GENDER

 patient was diagnosed with

    DMD
    DIAGNOSIS

 at

    age of 2
    AGE

.

    He
    GENDER

 has been

    treated with daily steroids
    MEDICATION

    since age 7 years
    AGE

.

    He
    GENDER

    lost the ability to arise from the floor and walk up steps
    NEG_FINDINGS

 at

    age 14
    AGE

 and

    lost ambulation
    SYMPTOMS

 by

    age 16
    AGE

.

    He
    GENDER

 was

    fitted with orthoses
    MEDICATION

 at

    age 16
    AGE

 following

    surgical correction of his lower extremity contractures
    MEDICATION

 and

    regained independent ambulation
    SYMPTOMS

. At

    age 20
    AGE

, he was able to

    stand independently in his orthoses
    MEDICATION

 and

    take steps with moderate support
    MEDICATION

. We conclude that a

    combination of daily steroids and orthoses
    MEDICATION

    prolongs ambulation
    MEDICATION

 beyond that of the natural history

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
DMD
DMD

lose ambulation
lost ambulation
regained independent ambulation


Unusual presentation as an adult onset painful myopathy in a Thai patient with Becker muscular dystrophy.

A Thai 37-years-old man presented with adult onset progressive proximal muscle weakness and generalized myalgia. Family history showed similar symptoms in several male relatives, compatible with X-linked recessive inheritance. Electromyography suggested myopathic process. Serum creatine kinase was highly elevated. Diagnosis of Becker muscular dystrophy (BMD) was confirmed by genetic testing. His symptoms responded well to steroid treatment. This report is of the first Thai patient with atypical presentation of BMD.

A

    Thai
    ETHNICITY

    37-years-old
    AGE

    man
    GENDER

 presented with

    adult onset progressive proximal muscle weakness
    SYMPTOMS

 and

    generalized myalgia
    SYMPTOMS

.

    Family history showed similar symptoms in several male relatives, compatible with X-linked recessive inheritance
    FAMILY

.

    Electromyography
    PARACLINICAL

 suggested

    myopathic process
    DIAGNOSIS

.

    Serum creatine kinase was highly elevated
    BIOCHEMICAL

. Diagnosis of

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 was confirmed by

    genetic testing
    PARACLINICAL

.

    His
    GENDER

 symptoms responded well to

    steroid treatment
    MEDICATION

. This report is of the first

    Thai
    ETHNICITY

 patient with

    atypical presentation of BMD
    SYMPTOMS

.

myopathic process
Becker muscular dystrophy (BMD)


Dexmedetomidine and fentanyl combination for procedural sedation in a case of Duchenne muscular dystrophy.

Duchenne muscular dystrophy, an X-linked disorder characterized by progressive muscle weakness, is the most common muscular dystrophy among children leading to death before the end of third decade. Anesthesia in such patients pose a great challenge due to various complications associated with it. The dreaded metabolic and clinical complications occur due to various inhalational anesthetics and succinylcholine in this subset of patients. We are reporting a child with diagnosed Duchenne muscular dystrophy who underwent excision of dentigerous cyst in oral cavity under procedural sedation with combination of dexmedetomidine and fentanyl and thus administration of general anesthesia was avoided.

    Duchenne muscular dystrophy
    DIAGNOSIS

, an

    X-linked disorder
    GENETICS

 characterized by

    progressive muscle weakness
    SYMPTOMS

, is the most common

    muscular dystrophy
    DIAGNOSIS

 among

    children
    AGE

 leading to

    death
    SYMPTOMS

    before the end of third decade
    AGE

.

    Anesthesia
    MEDICATION

 in such patients pose a great challenge due to various complications associated with it. The dreaded

    metabolic and clinical complications
    SYMPTOMS

 occur due to various

    inhalational anesthetics
    MEDICATION

 and

    succinylcholine
    MEDICATION

 in this subset of patients. We are reporting a

    child
    AGE

 with diagnosed

    Duchenne muscular dystrophy
    DIAGNOSIS

 who underwent

    excision of dentigerous cyst in oral cavity
    MEDICATION

 under

    procedural sedation with combination of dexmedetomidine and fentanyl
    MEDICATION

 and thus

    administration of general anesthesia was avoided
    NEG_FINDINGS

.

Duchenne muscular dystrophy
muscular dystrophy
Duchenne muscular dystrophy

progressive muscle weakness
death
metabolic and clinical complications


Macroglossia associated with 271 bp deletion in exon 50 of dystrophin gene.

Macroglossia is rare in patients of Duchenne muscular dystrophy (DMD), and its occurrence without any endocrinologic abnormality, seizures or an abnormal karyotype is even rarer. We describe a patient of DMD with isolated macroglossia with 271 bp deletion in exon 50 of the dystrophin gene and speculate a relationship in this regard.

    Macroglossia
    SYMPTOMS

 is rare in patients of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, and its occurrence

    without any endocrinologic abnormality
    NEG_FINDINGS

,

    seizures
    SYMPTOMS

 or an

    abnormal karyotype
    NEG_FINDINGS

 is even rarer. We describe a patient of

    DMD
    DIAGNOSIS

 with

    isolated macroglossia
    SYMPTOMS

 with

    271 bp deletion in exon 50 of the dystrophin gene
    GENETICS

 and speculate a relationship in this regard.

Macroglossia
seizures
isolated macroglossia

without any endocrinologic abnormality
abnormal karyotype


[Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy].

To identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD.

Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA). Biopsied muscle samples were examined with HE staining, immnostaining with anti-dystrophin antibody, and electronic microscopy.

MLPA assay suggested that both cases were probably due to non-deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed non-contiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti-dystrophin antibody and negative result with C-terminal anti-dystrophin antibody.

For patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.

To identify potential mutations in patients featuring

    Becker muscular dystrophy (BMD)
    DIAGNOSIS

 and to enhance the understanding of

    non-deletion/duplication mutations of the dystrophin gene
    GENETICS

 causing

    BMD
    DIAGNOSIS

.

Clinical data of two patients affected with

    BMD
    DIAGNOSIS

 were collected.

    Potential mutations in the dystrophin gene
    GENETICS

 were screened with

    multiplex ligation-dependent probe amplification assay (MLPA)
    PARACLINICAL

.

    Biopsied muscle samples
    PARACLINICAL

 were examined with

    HE staining
    PARACLINICAL

,

    immnostaining with anti-dystrophin antibody
    PARACLINICAL

, and

    electronic microscopy
    PARACLINICAL

.

    MLPA assay
    PARACLINICAL

 suggested that both cases were probably due to

    non-deletion/duplication mutations of the dystrophin gene
    GENETICS

.

    Light and electronic microcopy of skeletal muscle biopsies
    PARACLINICAL

 confirmed

    dystrophic changes
    SYMPTOMS

 in both patients. For patient A,

    immunostaining
    PARACLINICAL

 showed

    non-contiguous weak staining for most parts of sarcolemma
    MICROSCOPIC

. For patient B,

    immunostaining
    PARACLINICAL

 showed

    positive result with N-terminal anti-dystrophin antibody
    BIOCHEMICAL

 and

    negative result with C-terminal anti-dystrophin antibody
    NEG_FINDINGS

.

For patients with

    mild phenotypes
    SYMPTOMS

 but

    without dystrophin gene deletion/duplication
    NEG_FINDINGS

,

    muscle biopsy
    PARACLINICAL

 and

    immunochemistry
    PARACLINICAL

 are helpful for diagnosis and prognosis.


Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report.

Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental.

We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin.

Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

    Diamond-Blackfan anemia
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

 are two rare

    congenital anomalies
    DIAGNOSIS

. Both anomalies occurring in the same child is extremely rare.

    Allogeneic hematopoietic stem cell transplantation
    MEDICATION

 is a well-established therapy for

    Diamond-Blackfan anemia
    DIAGNOSIS

. However, in patients with

    Duchenne muscular dystrophy
    DIAGNOSIS

,

    stem cell therapy
    MEDICATION

 still remains experimental.

We report the case of a

    nine-year-old
    AGE

    boy
    GENDER

 of

    north Indian descent
    ETHNICITY

 with

    Diamond-Blackfan anemia
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

 who underwent

    successful allogeneic hematopoietic stem cell transplantation
    MEDICATION

.

    He
    GENDER

 is

    transfusion-independent
    NEG_FINDINGS

, and his

    Duchenne muscular dystrophy
    DIAGNOSIS

 has shown

    no clinical deterioration over the past 45 months
    NEG_FINDINGS

. His

    creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant
    BIOCHEMICAL

. The patient is

    100% donor chimera in the hematopoietic system
    MICROSCOPIC

, and his

    muscle tissue has shown 8% to 10.4% cells of donor origin
    MICROSCOPIC

.

Our patient's

    Diamond-Blackfan anemia
    DIAGNOSIS

 was cured by

    allogeneic hematopoietic stem cell transplantation
    MEDICATION

. The interesting clinical observation of a possible benefit in

    Duchenne muscular dystrophy
    DIAGNOSIS

 cannot be ruled out. However, further clinical follow-up with

    serial muscle biopsies
    PARACLINICAL

 and

    molecular studies
    PARACLINICAL

 are needed to establish this finding.

Diamond-Blackfan anemia
Duchenne muscular dystrophy
congenital anomalies
Diamond-Blackfan anemia
Duchenne muscular dystrophy
Diamond-Blackfan anemia
Duchenne muscular dystrophy
Duchenne muscular dystrophy
Diamond-Blackfan anemia
Duchenne muscular dystrophy


[Genotype-phenotype discordance in a Duchenne muscular dystrophy patient due to a novel mutation: insights into the shock absorber function of dystrophin].

Duchenne muscular dystrophy (DMD) is a genomic disorder characterized by progressive muscle wasting and weakness due to the absence or abnormal function of dystrophin; a protein that protects muscle cells from mechanical induced stress during contraction. Mutations in the DMD gene, may lead to different clinical phenotypes, collectively known as dystrophinopathies, of which DMD has the earliest onset and most severe progression.

We report a novel deletion of exons 24-41, predicted to maintain the reading frame and expected to result in a mild phenotype. Conversely, the patient has a severe DMD phenotype.

Our report supports the hypothesis that disruption of the gamma-actin-binding site located in the central rod domain plays a crucial role in the shock absorber function of dystrophin in muscle cells. Description of pathogenic variants in the DMD gene and the resulting phenotypes has important implications on the designing of molecular therapeutic approaches for DMD.

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 is a

    genomic disorder
    GENETICS

 characterized by

    progressive muscle wasting
    SYMPTOMS

 and

    weakness
    SYMPTOMS

 due to the

    absence or abnormal function of dystrophin
    BIOCHEMICAL

; a protein that

    protects muscle cells from mechanical induced stress during contraction
    SYMPTOMS

.

    Mutations in the DMD gene
    GENETICS

, may lead to different clinical phenotypes, collectively known as

    dystrophinopathies
    DIAGNOSIS

, of which

    DMD
    DIAGNOSIS

 has the earliest onset and most severe progression.

We report a

    novel deletion of exons 24-41, predicted to maintain the reading frame
    GENETICS

 and expected to result in a mild phenotype. Conversely, the patient has a

    severe DMD
    DIAGNOSIS

 phenotype.

Our report supports the hypothesis that

    disruption of the gamma-actin-binding site located in the central rod domain
    GENETICS

 plays a crucial role in the shock absorber function of dystrophin in muscle cells. Description of

    pathogenic variants in the DMD gene
    GENETICS

 and the resulting phenotypes has important implications on the designing of molecular therapeutic approaches for

    DMD
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
dystrophinopathies
DMD
severe DMD
DMD


[The use of rocuronium in a patient with Becker muscular dystrophy].

We report a case of thoracoscopic pulmonary resection for pneumothorax in a patient with Becker muscular dystrophy The sensitivity of nondepolarizing muscle relaxant in a patient with muscle dystrophy is reportedly higher than in a patient without muscle disease, and the duration of the effect is known to be prolonged. In a 26-year-old man (height 160 cm, weight 39 kg) with Becker muscular dystrophy, general anesthesia was induced with target controlled infusion of propofol (3.0 microg x ml(-1)) and 0.4 microg x kg(-1) of min(-1) of remifentanil. A small amount of rocuronium was also administered additionally until TOF ratio reached to 0%. Total amount of rocuronium was 20 mg (0.5 mg x kg(-1)) for intubation with a double-lumen tracheal tube. The duration of surgery was 68 min. We confirmed 84% recovery of TOF ratio 90 min after injection of rocuronium, and extubated the patient without reversal of rocuronium. We found that the maximum concentration in the plasma or effective site (Cp/Ce) of rocuronium was reached at the time of intubation.

We report a case of

    thoracoscopic pulmonary resection
    MEDICATION

 for

    pneumothorax
    DIAGNOSIS

 in a patient with

    Becker muscular dystrophy
    DIAGNOSIS

 The

    sensitivity of nondepolarizing muscle relaxant
    SYMPTOMS

 in a patient with

    muscle dystrophy
    DIAGNOSIS

 is reportedly higher than in a patient without

    muscle disease
    DIAGNOSIS

, and the duration of the effect is known to be prolonged. In a

    26-year-old
    AGE

    man
    GENDER

 (height 160 cm,

    weight 39
    SYMPTOMS

 kg) with

    Becker muscular dystrophy
    DIAGNOSIS

,

    general anesthesia
    MEDICATION

 was induced with

    target controlled infusion of propofol (3.0 microg x ml(-1)) and 0.4 microg x kg(-1) of min(-1) of remifentanil
    MEDICATION

. A

    small amount of rocuronium was also
    MEDICATION

 administered additionally until

    TOF ratio reached to 0%
    SYMPTOMS

.

    Total amount of rocuronium was 20 mg (0.5 mg x kg(-1)) for intubation with a double-lumen tracheal tube
    MEDICATION

. The

    duration of surgery
    MEDICATION

 was 68 min. We confirmed

    84% recovery of TOF ratio
    SYMPTOMS

 90 min after injection of

    rocuronium
    MEDICATION

, and

    extubated the patient without reversal of rocuronium
    MEDICATION

. We found that the

    maximum concentration in the plasma or effective site (Cp/Ce) of rocuronium
    BIOCHEMICAL

 was reached at the time of intubation.

pneumothorax
Becker muscular dystrophy
muscle dystrophy
muscle disease
Becker muscular dystrophy


Two closely spaced nonsense mutations in the DMD gene in a Malaysian family.

In Duchenne muscular dystrophy (DMD), identification of one nonsense mutation in the DMD gene has been considered an endpoint of genetic diagnosis. Here, we identified two closely spaced nonsense mutations in the DMD gene. In a Malaysian DMD patient two nonsense mutations (p.234S>X and p.249Q>X, respectively) were identified within exon 8. The proband's mother carried both mutations on one allele. Multiple mutations may explain the occasional discrepancies between genotype and phenotype in dystrophinopathy.

In

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

, identification of

    one nonsense mutation in the DMD gene
    GENETICS

 has been considered an endpoint of

    genetic diagnosis
    PARACLINICAL

. Here, we identified

    two closely spaced nonsense mutations in the DMD gene
    GENETICS

. In a

    Malaysian
    ETHNICITY

    DMD
    DIAGNOSIS

 patient

    two nonsense mutations (p.234S>X and p.249Q>X, respectively) were identified within exon 8
    GENETICS

.

    The proband's mother carried both mutations on one allele
    FAMILY

.

    Multiple mutations
    GENETICS

 may explain the occasional discrepancies between genotype and phenotype in

    dystrophinopathy
    DIAGNOSIS

.

Duchenne muscular dystrophy (DMD)
DMD
dystrophinopathy


The use of rocuronium in a patient with cystic fibrosis and end-stage lung disease made safe by sugammadex reversal.

While the pharmacology of sugammadex has been extensively reviewed, there is limited literature regarding its use in specific clinical settings. Several case reports describe its use in patients with the potential for postoperative respiratory dysfunction; in the settings of myasthenia gravis, Duchenne muscular dystrophy and myotonic dystrophy. We describe the use of sugammadex in a patient with severe bronchiectasis related to cystic fibrosis who required neuromuscular block for percutaneous endoscopic gastrostomy insertion. The use of rocuronium for neuromuscular block was preferred in order to avoid the potential complications associated with the use of suxamethonium. However we wished to ensure complete neuromuscular block reversal for this short duration procedure in this high-risk patient and also to avoid the side-effects of traditional reversal agents. We therefore planned in advance to use sugammadex for neuromuscular block reversal, and this approach proved successful. Overall, the combination of rocuronium and sugammadex improved perioperative surgical and anaesthetic management in this patient.

While the pharmacology of

    sugammadex
    MEDICATION

 has been extensively reviewed, there is limited literature regarding its use in specific clinical settings. Several case reports describe its use in patients with the potential for

    postoperative respiratory dysfunction
    SYMPTOMS

; in the settings of

    myasthenia gravis
    DIAGNOSIS

,

    Duchenne muscular dystrophy
    DIAGNOSIS

 and

    myotonic dystrophy
    DIAGNOSIS

. We describe the use of

    sugammadex
    MEDICATION

 in a patient with

    severe bronchiectasis
    DIAGNOSIS

 related to

    cystic fibrosis
    DIAGNOSIS

 who required

    neuromuscular block for percutaneous endoscopic gastrostomy insertion
    MEDICATION

. The

    use of rocuronium for neuromuscular block
    MEDICATION

 was preferred in order to avoid

    the potential complications associated with the use of suxamethonium
    SYMPTOMS

. However we wished to ensure

    complete neuromuscular block reversal
    SYMPTOMS

 for this

    short duration procedure
    MEDICATION

 in this high-risk patient and also to

    avoid the side-effects of traditional reversal agents
    NEG_FINDINGS

. We therefore planned in advance to use

    sugammadex for neuromuscular block reversal
    MEDICATION

, and this approach proved successful. Overall, the

    combination of rocuronium and sugammadex
    MEDICATION

 improved

    perioperative surgical and anaesthetic management
    MEDICATION

 in this patient.

myasthenia gravis
Duchenne muscular dystrophy
myotonic dystrophy
severe bronchiectasis
cystic fibrosis


Carrier woman of Duchenne muscular dystrophy mimicking inflammatory myositis.

Carrier woman of Duchenne muscular dystrophy (DMD) can mimic the inflammatory myositis in presenting symptoms. Two diseases should be differentiated by the clinical history, muscle biopsy and genetic study. There are few reports in which both histochemical and genetic study showed the possible link of overlapping inflammatory pathophysiology with dystrophinopathy. We report a 40-yr-old woman who presented with subacute proximal muscle weakness and high serum level of creatine kinase. She had a history of Graves' disease and fluctuation of serum liver aminotransferase without definite cause. MRI, EMG and NCV were compatible with proximal muscle myopathy. Muscle biopsy on vastus lateralis showed suspicious perifascicular atrophy and infiltration of mono-macrophage lineage cells complicating the diagnosis. Dystrophin staining showed heterogeneous diverse findings from normal to interrupted mosaic pattern. Multiple ligation probe amplification and X chromosome inactivation test confirmed DMD gene deletion mutation in exon 44 and highly skewed X inactivation.

Carrier woman of

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 can mimic the

    inflammatory myositis
    DIAGNOSIS

 in presenting symptoms. Two diseases should be differentiated by the clinical history,

    muscle biopsy
    PARACLINICAL

 and

    genetic study
    PARACLINICAL

. There are few reports in which both

    histochemical and genetic study
    PARACLINICAL

 showed the possible link of

    overlapping inflammatory pathophysiology
    SYMPTOMS

 with

    dystrophinopathy
    DIAGNOSIS

. We report a

    40-yr-old
    AGE

    woman
    GENDER

 who presented with

    subacute proximal muscle weakness
    SYMPTOMS

 and

    high serum level of creatine kinase
    BIOCHEMICAL

.

    She
    GENDER

 had a

    history of Graves' disease
    FAMILY

 and

    fluctuation of serum liver aminotransferase
    BIOCHEMICAL

    without definite cause
    NEG_FINDINGS

.

    MRI, EMG and NCV
    PARACLINICAL

 were compatible with

    proximal muscle myopathy
    DIAGNOSIS

.

    Muscle biopsy on vastus lateralis
    PARACLINICAL

 showed

    suspicious perifascicular atrophy
    SYMPTOMS

 and

    infiltration of mono-macrophage lineage cells
    MICROSCOPIC

 complicating the diagnosis.

    Dystrophin staining
    PARACLINICAL

 showed

    heterogeneous diverse findings from normal to interrupted mosaic pattern
    SYMPTOMS

.

    Multiple ligation probe amplification
    PARACLINICAL

 and

    X chromosome inactivation test
    PARACLINICAL

 confirmed

    DMD gene deletion mutation in exon 44
    GENETICS

 and

    highly skewed X inactivation
    GENETICS

.

Duchenne muscular dystrophy (DMD)
inflammatory myositis
dystrophinopathy
proximal muscle myopathy

DMD gene deletion mutation in exon 44
highly skewed X inactivation


Lesson of the month (1). Myotonic dystrophy and out-of-hospital arrest.

Myotonic dystrophy (MD) is an autosomal dominant disorder which affects both smooth and skeletal muscles. The incidence is approximately 1 in 8,000 births. It is the most common muscular dystrophy to manifest in adulthood, and the second most common skeletal muscle disorder after Duchenne MD. Cardiac rhythm disturbances are a common cause of death in these patients. This lesson describes a case in which a previously undiagnosed case of MD presented with an episode of ventricular fibrillation.

    Myotonic dystrophy (MD)
    DIAGNOSIS

 is an

    autosomal dominant disorder
    GENETICS

 which

    affects both smooth and skeletal muscles
    SYMPTOMS

. The incidence is approximately 1 in 8,000 births. It is the most common

    muscular dystrophy
    DIAGNOSIS

 to manifest in

    adulthood
    AGE

, and the second most common

    skeletal muscle disorder
    DIAGNOSIS

 after

    Duchenne MD
    DIAGNOSIS

.

    Cardiac rhythm disturbances
    SYMPTOMS

 are a common cause of

    death
    SYMPTOMS

 in these patients. This lesson describes a case in which a previously undiagnosed case of

    MD
    DIAGNOSIS

 presented with an

    episode of ventricular fibrillation
    SYMPTOMS

.

Myotonic dystrophy (MD)
muscular dystrophy
skeletal muscle disorder
Duchenne MD
MD


Pure intronic rearrangements leading to aberrant pseudoexon inclusion in dystrophinopathy: a new class of mutations?

We report on two unprecedented cases of pseudoexon (PE) activation in the DMD gene resulting from pure intronic double-deletion events that possibly involve microhomology-mediated mechanisms. Array comparative genomic hybridization analysis and direct genomic sequencing allowed us to elucidate the causes of the pathological PE inclusion detected in the RNA of the patients. In the first case (Duchenne phenotype), we showed that the inserted 387-bp PE was originated from an inverted ∼57 kb genomic region of intron 44 flanked by two deleted ∼52 kb and ∼1 kb segments. In the second case (Becker phenotype), we identified in intron 56 two small deletions of 592 bp (del 1) and 29 bp (del 2) directly flanking a 166-bp PE located in very close proximity (134 bp) to exon 57. The key role of del 1 in PE activation was established by using splicing reporter minigenes. However, the analysis of mutant constructs failed to identify cis elements that regulate the inclusion of the PE and suggested that other splicing regulatory factors may be involved such as RNA structure. Our study introduces a new class of mutations in the DMD gene and emphasizes the potential role of underdetected intronic rearrangements in human diseases.

We report on two unprecedented cases of

    pseudoexon (PE) activation in the DMD gene
    MICROSCOPIC

 resulting from

    pure intronic double-deletion events
    GENETICS

 that possibly involve

    microhomology-mediated mechanisms
    GENETICS

.

    Array comparative genomic hybridization analysis
    PARACLINICAL

 and

    direct genomic sequencing
    PARACLINICAL

 allowed us to elucidate the causes of the

    pathological PE inclusion detected in the RNA
    MICROSCOPIC

 of the patients. In the first case (

    Duchenne phenotype
    DIAGNOSIS

), we showed that

    the inserted 387-bp PE was originated from an inverted ∼57 kb genomic region of intron 44 flanked by two deleted ∼52 kb and ∼1 kb segments
    GENETICS

. In the second case (

    Becker phenotype
    DIAGNOSIS

), we identified in

    intron 56 two small deletions of 592 bp (del 1) and 29 bp (del 2) directly flanking a 166-bp PE located in very close proximity (134 bp) to exon 57
    GENETICS

. The key role of

    del 1 in PE activation
    GENETICS

 was established by using

    splicing reporter minigenes
    PARACLINICAL

. However, the analysis of mutant constructs

    failed to identify cis elements that regulate the inclusion of the PE
    NEG_FINDINGS

 and suggested that other splicing regulatory factors may be involved such as RNA structure. Our study introduces a new class of

    mutations in the DMD gene
    GENETICS

 and emphasizes the potential role of

    underdetected intronic rearrangements
    GENETICS

 in human diseases.


Recovery of systolic dysfunction in duchenne muscular dystrophy due to the point mutation c.4213C>T.

So far, a beneficial effect of combined angiotensin-converting enzyme inhibitors (ACEI) and β-blocker therapy for systolic dysfunction in Duchenne muscular dystrophy (DMD) has been reported only in patients in whom DMD was due to deletions in the dystrophin gene.

In a 24-year-old male with DMD due to the point mutation c.4213C>T (p.Gln1405X) in exon 30 of the dystrophin gene, cardiologic examination at the age of 23 years revealed asymptomatic severely reduced systolic dysfunction with a fractional shortening of 14% in the absence of dilated cardiomyopathy. A combined therapy with enalapril (2.5 mg/day) and bisoprolol (1.25 mg/day) was initiated. After a slow increase in the dosage to 10 mg enalapril/day and 2.5 mg bisoprolol/day, systolic dysfunction resolved to a fractional shortening of 26% already after 7 months.

This case shows that asymptomatic reduced systolic function also in patients with DMD due to a point mutation responds favourably to a combination therapy with ACEI and β-blockers.

So far, a beneficial effect of

    combined angiotensin-converting enzyme inhibitors (ACEI) and β-blocker therapy
    MEDICATION

 for

    systolic dysfunction
    SYMPTOMS

 in

    Duchenne muscular dystrophy (DMD)
    DIAGNOSIS

 has been reported only in patients in whom

    DMD
    DIAGNOSIS

 was due to

    deletions in the dystrophin gene
    GENETICS

.

In a

    24-year-old
    AGE

    male
    GENDER

 with

    DMD
    DIAGNOSIS

 due to the

    point mutation c.4213C>T (p.Gln1405X) in exon 30 of the dystrophin gene
    GENETICS

,

    cardiologic examination
    PARACLINICAL

 at the

    age of 23 years
    AGE

 revealed

    asymptomatic severely reduced systolic dysfunction with a fractional shortening of 14%
    SYMPTOMS

 in the

    absence of dilated cardiomyopathy
    NEG_FINDINGS

. A

    combined therapy with enalapril (2.5 mg/day) and bisoprolol (1.25 mg/day)
    MEDICATION

 was initiated. After a

    slow increase in the dosage to 10 mg enalapril/day and 2.5 mg bisoprolol/day
    MEDICATION

,

    systolic dysfunction resolved to a fractional shortening of 26% already after 7 months
    SYMPTOMS

.

This case shows that

    asymptomatic reduced systolic function
    SYMPTOMS

 also in patients with

    DMD
    DIAGNOSIS

 due to a

    point mutation
    GENETICS

 responds favourably to a

    combination therapy with ACEI and β-blockers
    MEDICATION

.


True euglycemic diabetic ketoacidosis in a person with type 2 diabetes and Duchenne muscular dystrophy.

True euglycemic diabetic ketoacidosis is a rare complication of diabetes. We describe a case of diabetic ketoacidosis in a male with type 2 diabetes and Duchenne muscular dystrophy. He presented with normal plasma glucose as a consequence of starvation, reduced muscle mass and increased body fat.

    True euglycemic diabetic ketoacidosis
    BIOCHEMICAL

 is a rare complication of

    diabetes
    DIAGNOSIS

. We describe a case of

    diabetic ketoacidosis
    DIAGNOSIS

 in a

    male
    GENDER

 with

    type 2 diabetes
    DIAGNOSIS

 and

    Duchenne muscular dystrophy
    DIAGNOSIS

.

    He
    GENDER

 presented with

    normal plasma glucose
    BIOCHEMICAL

 as a consequence of

    starvation
    SYMPTOMS

,

    reduced muscle mass
    SYMPTOMS

 and

    increased body fat
    SYMPTOMS

.

True euglycemic diabetic ketoacidosis
normal plasma glucose

diabetes
diabetic ketoacidosis
type 2 diabetes
Duchenne muscular dystrophy

starvation
reduced muscle mass
increased body fat