[SMC] Congenital Myasthenic Syndrome With Adult Onset Due to the Novel Heterozygous c.1399_1404del Variant in the Downst

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Cureus. 2025 Apr 4;17(4):e81690. doi: 10.7759/cureus.81690. eCollection 2025 Apr.

ABSTRACT

Although mutations in the downstream of tyrosine kinase-7 (DOK7) are one of the most common causes of congenital myasthenic syndrome (CMS) in children and adults, CMS in adults due to the heterozygous variant c.1399_1404del in DOK7 has not yet been reported. A 63-year-old woman had developed bilateral eyelid ptosis at the age of 50, followed by dysphagia shortly thereafter. At the age of 60, in addition to dysphagia, she developed dysarthria and decreased cough. Her sister had a history of right eyelid ptosis. Myasthenia gravis and myasthenic syndrome, motor neuron disease, and myopathy were ruled out in the index patient. Pyridostigmine, steroids, azathioprine, methotrexate, mycophenolate mofetil, and immunoglobulins were either ineffective or complicated by side effects. Genetic testing at the age of 61 years revealed the variants c.1399_1404del and c.54+32_54+33del in DOK7. Late-onset CMS was diagnosed, and salbutamol and later 3,4-diaminopyridine (3,4-DAP) were started, both of which showed a positive effect. This case shows that the DOK7 variant c.1399_1404del is probably pathogenic and responsible for late-onset CMS, either alone or together with the previously reported benign variant c.54+32_54+33del. Salbutamol in combination with 3,4-DAP could be beneficial in patients carrying the c.1399_1404del mutation in DOK7.

PMID:40330390 | PMC:PMC12050350 | DOI:10.7759/cureus.81690


Source: https://pubmed.ncbi.nlm.nih.gov/4033039 ... t9+e462414