Episodic Muscle Weakness, X-Linked

Clinical Features

Ryan et al. (1999) reported a family with clinical and pathologic features of a novel syndrome of episodic muscle weakness. Eight males in generations 2 and 4 demonstrated the features of the disorder, consistent with X-linked inheritance. Episodes of severe muscle weakness were typically precipitated by febrile illness and affected the facial and extraocular musculature, as well as the trunk and limbs, and resolved spontaneously over a period of weeks to months. Younger members of the family were normal between episodes but during relapses showed generalized weakness, ptosis, and fluctuations in strength. In some cases, fatigability could be demonstrated. The proband had late-onset chronic weakness and fatigability. The clinical phenotype had features suggestive both of the congenital myasthenic syndromes (see 254210) and of ion-channel disorders such as periodic paralyses (see 170400). Muscle biopsy in the index case demonstrated dilatation and focal proliferation of the sarcoplasmic reticulum.

Mapping

By linkage analysis in a family with episodic muscle weakness, Ryan et al. (1999) localized the disorder to an approximately 2.8-Mb region on Xp22.3, with a maximum 2-point lod score of 4.52 at a recombination fraction of 0.0.