A novel syndrome of episodic muscle weakness maps to Xp22.3

We describe a family with a novel disorder characterized by episodic muscle weakness and X-linked inheritance. Eight males in three generations demons trate the characteristic features of the disorder. Episodes of severe muscl e weakness are typically precipitated by febrile illness and affect the fac ial and extraocular musculature, as well as the trunk and limbs, and resolv e spontaneously over a period of weeks to months. Younger members of the fa mily are normal between episodes but during relapses show generalized weakn ess, ptosis, and fluctuations in strength. In some cases, fatigability can be demonstrated. The proband has late-onset chronic weakness and fatigabili ty. The clinical phenotype has features suggestive both of the congenital m yasthenic syndromes and of ion-channel disorders such as the periodic paral yses. We have localized the responsible gene to chromosome Xp22.3, with a m aximum two-point LOD score of 4.52 at a recombination fraction of .0, betwe en OACA2 and DXS9985.