Spectrum of Hereditary Neuropathies in Adult Patients From Serbia

Hereditary neuropathies are a group of genetically and phenotypically heterogeneous neuropathies. These are classified into: hereditary sensory motor neuropathy (HSMN) aka Charcot-Marie-Tooth disease (CMT), distal motor neuropathy (dMN), hereditary sensory autonomic neuropathy (HSAN), episodic neuropathies and polyneuropathy as part of a complex clinical presentation. The aim of this study was to determine final diagnoses in patients referred from the tertiary center in Serbia under suspicion of hereditary neuropathy.

This research included 340 patients directed for genetic testing from the Neurology Clinic, University Clinical Center of Serbia during the period from 2009 to 2023, who underwent complete genetic analyses available.

The most prominent demyelinating neuropathy was group consisted of patients with CMT1A (93 (27.3%)), followed by CMT1B (10 (2.9%)). In the group of patients with axonal form of the disease, the most prevalent was the one with pathogenic variant in HINT1 (18 (5.3%)). Nineteen (5.6%) patients have had variants in GJB1 gene. DMN group was composed of seven (2%) patients. HSAN was final diagnosis in 2 (0.6%) patients. Group of 16 (4.7%) patients have had neuropathy as part of a complex clinical presentation. In 70 (20.6%) patients no significant genetic variant was found, even though clinical presentation was highly suggestive of hereditary neuropathy.

In line with other populations, CMT1A was the most common cause of hereditary neuropathy in Serbia. The axonal cohort predominantly included patients with variants in the HINT1 gene, which represents a population-specific characteristic. These findings highlight the importance of targeted genetic analysis in diagnosing hereditary neuropathies in certain populations.