A recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course.

The ryanodine receptor RyR1 is the main sarcoplasmic reticulum Ca2+ channel in skeletal muscle and acts as a connecting link between electrical stimulation and Ca2+-dependent muscle contraction. Abnormal RyR1 activity compromises normal muscle function and results in various human disorders including malignant hyperthermia, central core disease, and centronuclear myopathy. However, RYR1 is one of the largest genes of the human genome and accumulates numerous missense variants of uncertain significance (VUS), precluding an efficient molecular diagnosis for many patients and families. Here we describe a recurrent RYR1 mutation previously classified as VUS, and we provide clinical, histological, and genetic data supporting its pathogenicity. The heterozygous c.12083C>T (p.Ser4028Leu) mutation was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, and either segregated with the disease in the dominant families or occurred de novo. The affected individuals essentially manifested neonatal or infancy-onset hypotonia, delayed motor milestones, and a benign disease course differing from classical RYR1-related muscle disorders. Muscle biopsies showed unspecific histological and ultrastructural findings, while RYR1-typical cores and internal nuclei were seen only in single patients. In conclusion, our data evidence the causality of the RYR1 c.12083C>T (p.Ser4028Leu) mutation in the development of an atypical congenital myopathy with gradually improving motor function over the first decades of life, and may direct molecular diagnosis for patients with comparable clinical presentation and unspecific histopathological features on the muscle biopsy.

Guillain-Barré syndrome during childhood: particular clinical and electrophysiological features.

INTRODUCTION: Guillain-Barré syndrome (GBS) has some specific characteristics in children. METHODS: In this study we reviewed the clinical, laboratory, electrophysiological, and prognosis features of the 19 children diagnosed with GBS at Nantes University Hospital from 2000 to 2011. RESULTS: Gait disturbance and leg pain were the most frequent presenting symptoms. Electrophysiological examinations revealed significant abnormalities even when performed within the first week after onset. Decreased distal CMAP amplitude was noted in 89% of cases. The pattern indicated an acute inflammatory demyelinating polyneuropathy in 95% of cases and acute motor axonal neuropathy in the remaining 5%. About two-thirds of the children were treated with intravenous immunoglobulin. After >1 year of follow-up, 17 patients had complete recovery. CONCLUSION: Gait disorder, leg pain, a high rate of distal conduction block, and a good prognosis are among the main specific features of GBS in childhood.