Electrocardiographic changes in cases of duchenne muscular dystrophy

BackgroundDuchene muscular dystrophy is an x-linked recessive progressive muscular disease. It presents in first year of life and is fatal by second decade mostly because of respiratory involvement and in 10% case because of cardiac failure. The cardiac involvement usually occurs after 10 years age. The incidence of cardiac involvement increases with increasing age affecting all patients by age of 18 years.Duchene muscular dystrophy(DMD) usually leads to dilated cardiomyopathy (DCM), congestive cardiac failure, arrhythmias, & sudden cardiac death. DMD may be associated with various ECG changes like sinus tachycardia, reduction of circadian index, decreased heart rate variability, short PR interval, right ventricular hypertrophy, S-T segment depression and prolonged QTc. Rarely it might be associated with Wolf Parkinson White syndrome(WPW syndrome). WPW syndrome is characterized by short PR interval, delta wave, and wide QRS complex and is a surface evidence of accessory pathway. It might be associated with supraventricular tachycardia and sudden cardiac death from ventricular tachycardia.AimTo study ECG findings in cases of Duchenne muscular dystrophy. Materials and methodsThe study was conducted at Pediatric cardiology department, Prince Salman Heart Centre Riyadh. All patients diagnosed as Duchenne muscular dystrophy were included in the study. The diagnostic criteria were clinical, biochemical and confirmed by PCR. All patients underwent 12 lead ECG and long lead II in recumbent posture and 24h holter monitoring and echocardiogram. The 24h holter was applied to all patients. The were given a diary to record any symptoms like palpitation, syncope, chest pain or dyspnea during 24 holter monitoring. The holters were reviewed for heart rate and presence of any ectopics or arrhythmias. The electrocardiogram of all patients were reviewed and following parameters were noted ; characteristics heart rate, R waves, waves, R–S ratio, PR interval, delata wave, Q waves, QT interval, T wave, ST segment. The aforementioned ECG parameters were studied and measured manually and compared with published standard age matched normal values. The abnormal were findings were defined if were away from minimal or maximal limits for that age.ResultsA total of 20 patients were studied. All were male. The mean age of patients was 10 years. The mean weight of patients was 34.5kg. Majority of patients (75%) were where wheelchair bound and 25% were ambulatory. The ECG abnormalities were noted in 80% of patients. Sinus tachycardia was present in 60% of patients. Tall R waves were present in 45% of patients with RS ratio more than 1 in lead V1 as well as deep S waves in leads V5 and V6.Short PR interval was noted in 3(15%) of patients. One patient had was diagnosed as WPW syndrome and had short PR interval, delta wave and wide QRS complex. 24h holter monitoring was normal in all patients.DiscussionThe most frequent electrocardiographic findings described in cases of Duchenne muscular dystrophy are sinus tachycardia and tall R waves in right precordial leads as seen in our study. Similar findings are also observed in female carriers of Duchenne muscular dystrophy gene. The presence of sinus tachycardia may suggest cardiac dysfunction or autonomic dysregulation in these cases. Other interesting finding in our cases was short PR interval in 3 cases(15%) and presence of WPW syndrome features in one patient. We planned further study in these patients to correlate clinical, biochemical, echo and ECG findings

Hepatocerebral form of mitochondrial DNA depletion syndrome due to mutation in MPV17 gene

Mitochondrial DNA depletion syndromes (MDSs) are autosomal recessive diseases characterized by a severe decrease in mitochondrial DNA content leading to dysfunction of the affected organ. Autosomal recessive mutations in MPV17 have been identified in the hepatocerebral form of MDS. We describe the clinical features, biochemical and molecular results of a Saudi infant with a new mutation of MPV17 and compared the features to those of previously reported cases. We stress the importance of such rare cases particularly in countries with high consanguineous marriage rate

Clinical, Pathologic, and Mutational Spectrum of Dystroglycanopathy Caused by LARGE Mutations

Dystroglycanopathies are a subtype of congenital muscular dystrophy of varying severity that can affect the brain and eyes, ranging from Walker-Warburg syndrome with severe brain malformation to milder congenital muscular dystrophy presentations with affected or normal cognition and later onset. Mutations in dystroglycanopathy genes affect a specific glycoepitope on α-dystroglycan; of the 14 genes implicated to date, LARGE encodes the glycosyltransferase that adds the final xylose and glucuronic acid, allowing α-dystroglycan to bind ligands, including laminin 211 and neurexin. Only 11 patients with LARGE mutations have been reported. We report the clinical, neuroimaging, and genetic features of 4 additional patients. We confirm that gross deletions and rearrangements are important mutational mechanisms for LARGE. The brain abnormalities overshadowed the initially mild muscle phenotype in all 4 patients. We present the first comprehensive postnatal neuropathology of the brain, spinal cord, and eyes of a patient with a homozygous LARGE mutation at Cys443. In this patient, polymicrogyria was the predominant cortical malformation; densely festooned polymicrogyria were overlaid by a continuous agyric surface. In view of the severity of these abnormalities, Cys443 may be a functionally important residue in the LARGE protein, whereas the mutation p.Glu509Lys of Patient 1 in this study may confer a milder phenotype. Overall, these results expand the clinical and genetic spectrum of dystroglycanopathy