Congenital myasthenic syndrome type 2C in a neonate: Redefining the phenotype of CHRNB1‐related myasthenic syndromes

Abstract Objective We present a neonate with generalized weakness due to autosomal recessive congenital myasthenic syndrome type 2C (CMS2C) resulting from a compound heterozygous mutation in the CHRNB1 gene. Patient description Our patient was determined by multiple methodologies to have a diagnosis of CMS2C (OMIM #616314). Whole‐genome sequencing revealed two distinct variants in the CHRNB1 gene (OMIM *100710): a maternally inherited 2 kb pathogenic microdeletion on chromosome 17p13.1 and a paternally inherited intronic deletion (c.1218‐9_1218‐7) that was reported by the laboratory as a variant of unknown significance. Conclusions CMS2C is a rare autosomal recessive genetic condition associated with early‐onset muscle weakness. Our patient had a paternally inherited deletion in CHRNB1 (c.1218‐9_1218‐7) that was initially described as a variant of unknown significance. We suggest this finding is “likely pathogenic,” as this aberration has not been commonly described. He also had a partial deletion of CHRNB1 in the maternally inherited allele, which provides further evidence that partial gene deletions may be a more common molecular mechanism than previously known for this condition. The combination of the clinical presentation and electrophysiologic data allowed us to understand the molecular findings and ultimately diagnose CMS2C in our patient.