Genotypic And Phenotypic Features of Patients with GJB1 Mutations: Single Center Experience (P11-8.003)

Abstract

<h3>Objective:</h3> To describe the clinical and genetic characteristics of patients with <i>GJB1</i> mutations in Turkey. <h3>Background:</h3> <i>GJB1</i> mutations are the most common cause of X-linked Charcot-Marie-Tooth (CMT) disease. Typical manifestation includes distal muscle weakness and atrophy in the lower limbs. On the other hand, additional clinical features, such as stroke-like episodes, vocal cord paralysis, and hearing loss, can be observed. <h3>Design/Methods:</h3> Herein, we evaluated the clinical and genetic features of 29 patients from 23 unrelated families with <i>GJB1</i> mutation at the Neuromuscular Unit of the Istanbul Faculty of Medicine, Istanbul University. <h3>Results:</h3> Eight patients were female. The mean age of onset was 19.0 ± 12.0 (between 3 and 53 years). Females (27.3 ± 13.2) had later disease onset than males (15.4 ± 11.4). The most common presenting symptom was distal muscle weakness and foot deformities (21 patients), followed by foot pain (4 patients) and hand tremor (3 patients). Family history was absent in six patients. Two patients had immunosuppressive treatment for a misdiagnosis of inflammatory neuropathy. In neurological examination, all but two female patients had distal weakness in the lower extremities, and 24 had upper extremity weakness. The most frequent skeletal deformity was pes cavus (25 patients), followed by hammer toes (16 patients). Nine patients had hand tremor, and one had vocal cord paralysis. One patient had a history of stroke-like episodes, and one had multiple-sclerosis like cranial and spinal cord MRI lesions. In a mean disease duration of 22.5 ± 14.6 years all patients were ambulatory. The mean median motor nerve conduction velocity was 36.5 ± 8.2, consistent with intermediate-type CMT disease. Eighteen different mutations were identified in the <i>GJB1</i> gene. <h3>Conclusions:</h3> Our patients exhibited diverse phenotypic features regarding the disease onset and additional symptoms. Moreover, genotypic features were also heterogeneous, considering the identified mutations were scattered throughout the gene. <b>Disclosure:</b> Dr. Parman has nothing to disclose. Arman Cakar has nothing to disclose. Ayse Candayan has nothing to disclose. Dr. Durmus has nothing to disclose. Esra Battaloglu has nothing to disclose.