Familial Periodiic Paralysis + CMT in a 7 Generation Family

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Abstract from Arch Neurol January 2005 Vol. 62 No. 1;62:135-138.

Familial Periodic Paralysis and Charcot-Marie-Tooth Disease in a 7-Generation

Family

Fuki M. Hisama, MD

Background A family with a complicated constellation of neurologic findings,

including neuropathy, myotonia, and periodic paralysis, has been described in 4

studies in the medical literature since 1934. The underlying cause of their

disease has been the subject of considerable speculation and has never been

identified until now.

Objective To identify the molecular basis of this family’s neurologic disease.

Design The coding regions of 6 genes that cause peripheral neuropathy and

regions of the muscle sodium channel gene (SCN4A) were sequenced.

Results A novel missense mutation (Arg67Pro) in the myelin protein zero gene

was identified in 2 patients with Charcot-Marie-Tooth disease, and a common

missense mutation (Thr704Met) was identified in the SCN4A gene in 4 family

members. We discuss the difficulties of genotype-phenotype correlation in this

family.

Conclusions These findings indicate that 2 independent mutations segregating in

this family are responsible for the puzzling clinical picture.

Author Affiliation: Department of Neurology, Neurogenetics Program, Yale

University School of Medicine, New Haven, Conn.