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A large german kindred with cold‐aggravated myotonia and a heterozygous A1481D mutation in the SCN4A gene
Author(s) -
Schoser Benedikt G. H.,
Schröder J. Michael,
Grimm Timo,
Sternberg Damien,
Kress Wolfram
Publication year - 2007
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20733
Subject(s) - myotonia , muscle biopsy , missense mutation , weakness , myotonic dystrophy , medicine , muscle stiffness , endocrinology , anatomy , genetics , mutation , biology , biopsy , gene , stiffness , structural engineering , engineering
Muscle sodium‐channel disorders cover a spectrum of rare myotonic diseases. In a German family with 17 affected individuals in four generations, we identified a heterozygous missense mutation in exon 24 A1481D (c.4442 C>A) of the voltage‐gated sodium channel gene ( SCN4A ) alpha subunit. Phenotypes of 12 family members were characterized by a mild myotonia with cold sensitivity but without paramyotonia. The index patient presented with fluctuating cold‐ and exercise‐induced stiffness of ocular, facial, and distal muscles. The myotonia became more severe at the age of 22 years. His father had had cold‐ and exercise‐induced periodic weakness with fluctuating myotonia since age 10. Later he developed a more severe, purely exercise‐ and cold‐aggravated myotonia of arms, hands, and facial muscles. The father's mother presented with cold‐induced myotonia until age 65, when progressive weakness of proximal limb muscles developed. Her muscle biopsies revealed considerable myopathic changes with a variety of fine structural alterations. This study presents a family with cold‐aggravated myotonia and progression of myopathic changes in the muscle biopsy with increasing age. In older patients, sodium channelopathies may mimic the phenotypic features of myotonic dystrophy type 2. Muscle Nerve, 2007