Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy.

Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.

Sublingual Atropine Sulfate Use for Sialorrhea in Pediatric Patients.

Sialorrhea is a frequent problem and may lead to aspiration in patients with swallowing dysfunction. We aimed to assess the effectiveness and safety of sublingual atropine sulfate treatment in pediatric patients with sialorrhea. The medical records of patients who had received sublingual atropine sulfate between January 2015 and January 2016 were reviewed retrospectively. The demographic properties, diagnosis, invasive or noninvasive mechanical ventilation need, and the presence of tracheotomy were assessed. Response rates to sublingual atropine were measured using the Teacher Drooling Scale (TDS). Pre and post-treatment drooling scores were compared. Atropine sulfate ampoule was administered at 20 µg/kg/dose. Minimum dose was 0.25 mg, while maximum dose was 0.03 mg/kg.Thirty-five pediatric patients with sialorrhea who had received sublingual atropine sulfate were identified; however, TDS scores had been recorded in only 20 of them. The median age of the patients was 25 months (3-78 months; 7 girls, 13 boys). Sixteen (80%) patients were on invasive mechanical ventilation and seven (30%) had tracheotomy. Nineteen patients had a neurodevelopmental disorder and only one patient had oral and esophageal lesions due to corrosive material intake. The median TDS score prior to sublingual atropine sulfate treatment was 5, and it decreased to 3 on the second day of treatment, a change that was statistically significant ( p < 0.001). No side effects were observed. Sublingual atropine sulfate is safe and effective in the short-term treatment of sialorrhea; however, randomized placebo controlled and long-term follow-up studies are necessary.

Effects of Adrenocorticotropic Hormone Treatment on Heart Muscle in Patients with Infantile Spasm.

Background and aim Infantile spasm (IS) is a common epileptic syndrome of childhood epilepsies. The most effective treatment for IS is adrenocorticotropic hormone (ACTH). We hypothesized that ACTH treatment might change myocardial systolic and diastolic performance and cause cardiovascular side effects. This study aims to evaluate the effects of ACTH treatment on the heart muscle in IS patients. Materials and methods Eighteen newly diagnosed patients with IS participated in the study. ACTH (Synacthen® Depot) administered for two months in a total of 18 doses. A twelve-channel-surface electrocardiogram (ECG) and echocardiography performed in all patients before ACTH treatment, the second month after ACTH treatment (end of treatment), and two months later (after treatment). The systolic and diastolic myocardial functions were assessed by conventional and tissue Doppler imaging (TDI). Results The mean age of the patients was 8.1 months, and the patient group consisted of five female and 13 male subjects. None of the patients had clinically significant arrhythmia during treatment. After treatment, the mean heart rates of the patients significantly decreased (p=0.02), the systolic and diastolic blood pressures of patients did not change. We observed mild septal hypertrophy and an increase in the left ventricle mass index with ACTH treatment. Septal hypertrophy did not show progression until the fourth month after treatment. After ACTH treatment, patients had higher left ventricular myocardial performance index and lower E' and A' values at the mitral lateral annuli, however, these values didn't statistically significant from pretreatment values. Conclusion The low dose and short duration ACTH treatment in IS patients may cause subclinical myocardial hypertrophy. ACTH treatment has no significant side effects on cardiac functions.

A Rare Cause of Autism Spectrum Disorder: Megaconial Muscular Dystrophy.

Megaconial congenital muscular dystrophy (OMIM 602541) is defined by early-onset hypotonia, mildly elevated serum creatine kinase (CK) levels, muscle wasting, cardiomyopathy, psychomotor developmental delay and intellectual disability. The disease is caused by loss-of-function mutations in Choline kinase beta gene (CHKB) and has specific muscle biopsy findings. Here we investigate two patients with weakness of proximal muscles and generalized muscle atrophy, skin changes, agressiveness, social communication and empathy difficulties. Both patients had mildly elevated serum CK levels. Whole exome sequencing (WES) performed for both patients and homozygous c.818+1G>A and homozygous c.1031+1G>A variants were detected in patient 1 and patient 2, respectively. We would like to draw the attention of autism spectrum disorder in early diagnosis of congenital muscular dystrophies.