Myasthenic Syndrome, Congenital, 2c, Associated With Acetylcholine Receptor Deficiency
A number sign (#) is used with this entry because of evidence that congenital myasthenic syndrome associated with acetylcholine receptor (AChR) deficiency-2C (CMS2C) is caused by compound heterozygous mutation in the CHRNB1 gene (100710) on chromosome 17p13. One such family has been reported.
Mutation in the CHRNB1 gene can also cause slow-channel congenital myasthenic syndrome-2A (CMS2A; 616313).
DescriptionCongenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized clinically by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).
For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
Clinical FeaturesQuiram et al. (1999) reported 3 sibs with CMS and severe AChR deficiency. The proband, 8 years of age at the time of report, had severe myasthenic symptoms from birth, requiring frequent ventilation and enteric alimentation through a gastrostomy. She had a decremental electromyographic response on stimulation of motor nerves and responded partially to acetylcholinesterase inhibitors. Tests for anti-AChR antibodies were negative. The parents were unaffected. Electrophysiologic studies showed that the MEPP and MEPC were both decreased, with normal quantal release. Analysis of affected muscle fibers showed an increased number of small endplate regions distributed over a 3-fold increased span of the muscle fiber surface. Nerve terminal size and the postsynaptic area of folds and clefts were both decreased compared to normal.
InheritanceThe transmission pattern of CMS2C in the family reported by Quiram et al. (1999) was consistent with autosomal recessive inheritance.
Molecular GeneticsIn 3 sibs with CMS2C, Quiram et al. (1999) identified compound heterozygosity for 2 mutations in the CHRNB1 gene (100710.0003; 100710.0004).