Congenital Myasthenic Syndrome With Adult Onset Due to the Novel Heterozygous c.1399_1404del Variant in the Downstream of Tyrosine Kinase-7 (DOK7): A Case Report

TL;DR

A 63-year-old woman with a novel DOK7 gene variant was diagnosed with late-onset congenital myasthenic syndrome, and treatment with salbutamol and 3,4-DAP showed improvement.

Contribution

The paper reports the first case of adult-onset CMS caused by the novel DOK7 variant c.1399_1404del and suggests effective treatment options.

Findings

The DOK7 variant c.1399_1404del is likely pathogenic for late-onset CMS.

Salbutamol and 3,4-DAP treatment improved symptoms in the patient with the DOK7 mutation.

The c.54+32_54+33del variant may contribute to CMS when combined with c.1399_1404del.

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.

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