Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes

Abstract

SCCMS mutations may show a recessive inheritance pattern and variable penetrance. A diagnosis of SCCMS should not be ruled out in cases of CMS with an apparent recessive inheritance pattern.

The Therapy of Congenital Myasthenic Syndromes

“…Some slow-channel syndromes with less prolonged opening events of the AChR channel are determined by recessive inheritance. 18 All other CMSs identified to date are caused by recessive loss-of-function mutations in various endplate-specific proteins.…”

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

“…2). There is a single reported case of autosomal recessive SCCMS, in which an L78P mutation minimally prolongs channel opening events but the mutant channel arising from a single allele is not sufficient to cause disease (Croxen et al, 2002). In general, dominantly inherited disorders, including SCCMS, tend to present after adolescence and have a relatively mild course.…”

Therapeutic Strategies in Congenital Myasthenic Syndromes

“…These are inherited disorders, caused by various genetic defects, and all but the slow-channel CMS by recessive inheritance. [1][2][3][4][5] To date, mutations in 10 different genes have been found to cause a CMS: CHAT, coding for the presynaptic choline acetyltransferase 6 ; COLQ, coding for the endplate acetylcholine esterase 7,8 ; CHRNA1, CHRNB1, CHRND, and CHRNE coding for four different AChR subunits 9,10 ; RAPSN, coding for the postsynaptic protein rapsyn 11 ; MUSK, coding for the muscle-specific kinase 12 ; DOK7, coding for the downstream of kinase 7 protein 13 ; and SCN4A, coding for the postsynaptic voltage-gated sodium channel Na v 1.4. 14…”