Genetic variants among patients with motor neuron disease in Lithuania - a retrospective single-center study

Motor neuron disease (MND) comprises several clinical phenotypes, with amyotrophic lateral sclerosis (ALS) being the most common. Despite the identification of over 40 ALS-associated genes, the pathogenesis remains complex and polygenic. This study evaluated the clinical phenotypes and prevalence of genetic causes in MND patients in Lithuania. We conducted a retrospective single-center study at a tertiary care clinic on patients with MND. Clinical and molecular genetic data were analyzed. The study included 53 patients with a mean age at symptom onset of 55 years. Most patients (43/53; 77.4%) were diagnosed with ALS, and the most common onset was spinal (39/53; 73.6%). The frequency of pathogenic or likely pathogenic genetic variants was 15.7% (8/51). C9orf72 hexanucleotide repeat expansion was detected in 5.9% (3/51) of patients. Next-generation sequencing was performed in 49 patients, of whom 5 (10.2%) had pathogenic or likely pathogenic variants, including pathogenic variants in the SOD1 and NEK1 genes and likely pathogenic variants in the FUS. The most common finding was C9orf72 hexanucleotide repeat expansion, followed by variants in SOD1 and FUS genes. The genetic spectrum was broadly similar to internationally recognized MND-associated genes, though formal comparisons were not performed due to the absence of a control group. These results emphasize the importance of systematic genetic testing in clinical practice and contribute to the limited data on the genetic spectrum of MND in the Baltic region.