Abstract

Non-dystrophic myotonias are a group of rare neuromuscular diseases linked to SCN4A or CLCN1. Among the subtypes, myotonia permanens, associated with the Gly1306Glu variant of SCN4A, is a relatively less frequent but more severe form. Most reports of non-dystrophic myotonias describe European populations. Therefore, to expand the genetic and phenotypic spectrum of this disorder, we evaluated 30 Chilean patients with non-dystrophic myotonias for associated variants and clinical characteristics. SCN4A variants were observed in 28 (93%) of patients, including 25 (83%) with myotonia permanens due to the Gly1306Glu variant. Myotonia permanens was inherited in 24 (96%) patients; the mean age of onset was 6 months, and the initial symptoms were orbicularis oculi myotonia in 17 (74%) patients and larynx myotonia in 12 (52%) patients. The extraocular muscles were involved in 11 (44%) patients, upper limbs in 20 (80%), and lower limbs in 21 (84%). Thirteen (52%) patients experienced recurrent pain and 10 (40%) patients reported limitations in daily life activities. Carbamazepine reduced myotonia in eight treated patients. The high frequency of the Gly1306Glu variant in SCN4A in Chilean patients suggests a founder effect and expands its phenotypic spectrum.