A large German kindred with cold-aggravated myotonia and a heterozygous A1481D mutation in the SCN4A gene.
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.
Schoser
Benedikt G H
BG
Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University Munich, Ziemssenstrasse 1a, 80336 Munich, and Department of Neuropathology, University Hospital, RWTH Aachen, Germany. bschoser@med.uni-muenchen.de
Schröder
J Michael
JM
Grimm
Timo
T
Sternberg
Damien
D
Kress
Wolfram
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000737:chemistry / Q000235:genetics; D019943:Amino Acid Substitution; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics; D003080:Cold Temperature; D004252:DNA Mutational Analysis; D005260:Female; D005858:Germany; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009224:Myotonia Congenita / Q000235:genetics* / Q000473:pathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010375:Pedigree; D015222:Sodium Channels / Q000235:genetics*
D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels; D001224:Aspartic Acid; D000409:Alanine