[SMC] Suspected Adult-Onset Congenital Myasthenic Syndrome Associated With a Heterozygous CHRND Variant in a Patient Wit

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Am J Case Rep. 2026 Jun 22;27:e952887. doi: 10.12659/AJCR.952887.

ABSTRACT

BACKGROUND Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous disorder of neuromuscular transmission, with more than 35 associated genes. Although CMS typically presents at birth or in early childhood, adult-onset forms are increasingly recognized and frequently mimic seronegative autoimmune myasthenia gravis, causing diagnostic delay. Its prevalence (2.8-14.8 per million) is probably underestimated, particularly for mild, late-onset, or atypical phenotypes. CASE REPORT A 42-year-old man with well-controlled seropositive rheumatoid arthritis presented with progressive fatigue, fluctuating proximal weakness (Medical Research Council grade 4/5 with fatigability), bilateral ptosis, and intermittent diplopia. Nerve conduction studies, repetitive nerve stimulation, and electromyography were normal, and a comprehensive autoimmune and myositis antibody panel was negative, prompting genetic testing. Whole-exome and whole-genome sequencing identified a heterozygous pathogenic CHRND variant; additional variants of uncertain or unrelated significance were also detected. Because CHRND-related CMS is classically autosomal recessive and single-fiber electromyography was not performed, a single heterozygous variant cannot be regarded as confirmatory, and the diagnosis is considered suspected rather than definitive. Pyridostigmine produced clinically meaningful improvement-reduced ptosis, resolved diplopia, and improved endurance-that was sustained at the 6-week follow-up. CONCLUSIONS CMS should be considered in adults with fatigable weakness and atypical neuromuscular features once autoimmune causes are excluded; however, a single heterozygous variant without confirmatory electrophysiology limits diagnostic certainty. To our knowledge, this is the first report of a suspected CHRND-associated adult-onset CMS with seropositive rheumatoid arthritis. Broad genetic testing is valuable when phenotype and serology diverge, but results must be interpreted cautiously alongside electrophysiological confirmation before a definitive diagnosis.

PMID:42324739 | DOI:10.12659/AJCR.952887


Source: https://pubmed.ncbi.nlm.nih.gov/4232473 ... 3&v=2.20.0