A large German kindred with cold-aggravated myotonia and a heterozygous A1481D mutation in the SCN4A gene.

Abstract:

: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.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Schoser BG,Schröder JM,Grimm T,Sternberg D,Kress W

doi

10.1002/mus.20733

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

599-606

issue

5

eissn

0148-639X

issn

1097-4598

journal_volume

35

pub_type

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