Objective:

To describe the clinical and genetic characteristics of patients with distal hereditary motor neuropathy in Turkey.

Background:

Distal hereditary motor neuropathies (dHMN) are rare genetic disorders characterized by degeneration of the peripheral motor nerves. Around 30 causative genes have been identified to cause dHMN. However, only about 30% of patients receive a genetic diagnosis despite the advances in molecular genetics. Understanding the genetic distribution in underrepresented populations is essential to closing the gap in genetic diagnosis rate.

Design/Methods:

Herein, we evaluated the clinical and genetic features of the 30 patients from 26 families with dHMN followed at the Neuromuscular Unit of Istanbul Faculty of Medicine, Istanbul University.

Results:

Nine patients were female. The mean age of onset was 14.33 ± 9.75 (between 2 and 47 years). Lower limb or foot deformities were the presenting symptom in all patients, except for two with cramps and one with hand weakness. Twenty-one patients were born to consanguineous marriages, and family history was positive in 9 probands. The mean age at the last examination was 26.57 ± 10.31 (between 15 and 57 years). In 28 patients, neurological examination showed various degrees of symmetric distal lower extremity weakness. In contrast, isolated distal upper extremity weakness was found in 2 patients harbouring SORD or GARS variants. Pathogenic variants were distributed to 14 genes, including ultra-rare causes of dHMN such as NRCAM and HADHB. The most frequently mutated gene was SORD (8 families), followed by HINT1 (5 families) and DNAJB2 (3 families). Interestingly, the disease is caused by biallelic variants in 23 families and monoallelic in 3.

Conclusions:

Our study showed that the genetic distribution of dHMN in our cohort is heterogeneous. Unlike similar studies performed in European countries, biallelic variants predominated our cohort. Phenotypical features were quite uniform compared to genetic heterogeneity.