Congenital Myopathy-1B due to RYR 1 Gene Mutation in Three Libyan Families

Abstract

Abstract Introduction  We report a series of patients in three different Libyan families diagnosed with congenital myopathy to study the wide clinical variability between these families, and the genetic heterogeneity. Description of Cases  We describe six patients, one patient presented with severe neonatal-onset RYR1-associated myopathy while the other five patients came mainly due to delay in motor development; genetic testing confirmed the diagnosis of CMY-1B disease due to RYR1 mutation in all patients. Clinical features of congenital widely varied between the families ranging from profound hypotonia during the neonatal period in one family to a motor delay and abnormal gait during childhood in other two families. Whereas the clinical picture is quite similar in the patients of same family, the patient who presented with severe neonatal presentation of RYR1-associated myopathy also had gastrostomy feeding, respiratory involvement, clubfeet, cleft palate, and undescended testes. The five patients who presented due to delay in motor development all were ambulatory without the need of support, except the youngest one aged 4 years still walking with support. The genetic study in the form of whole-exon sequencing as well as next-generation sequencing showed homozygosity of a gene mutation in five patients and a compound heterozygosity in one patient which presented with neonatal severe hypotonia. Conclusion  CMY-1B disease is a rare autosomal dominant and recessive genetic disorder that has variable clinical presentations. The early diagnosis is very important for genetic counseling as well as avoiding malignant hyperthermia. We also report rare and unusual presentations that may further delay the diagnosis.