Homozygosity of a Founder Variant c.1508dupC in DOK7 Causes Congenital Myasthenia With Variable Severity

Abstract

Background and Objectives Description of 15 patients with the same variant in DOK7 causing congenital myasthenic syndrome (CMS).MethodsNine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations. Results All patients were identified with the c.1508dupC variant in DOK7, of whom 13 were homozygous and 2 patients compound heterozygous. Only 2 patients had limb girdle phenotype, while all adult patients also had ptosis, ophthalmoplegia, facial weakness, as well as inspiratory stridor. Pediatric patients had severe respiratory insufficiency and feeding difficulties at birth. Discussion The disease severity in our patients varied extensively from ventilator or wheelchair dependence to mild facial weakness, ptosis, and ophthalmoparesis. Most of the patients had normal transmission in conventional 3 Hz stimulation electrophysiologic studies, making the diagnosis of CMS challenging. Our cohort of adult and pediatric patients expands the phenotype of DOK7 CMS and shows the importance of correct and early diagnosis.