Dados do Trabalho

Título

Expanding the phenotypic spectrum in of Hereditary Spastic Paraplegia type 6 (SPG6): a case report of spasticity, epilepsy, motor axonal neuropathy, and disatropophonia.

RESUMO

Case Report: A 70-years-old man presented with a long standing history of complex hereditary disorder characterized by spastic paraplegia, epilepsy and axonal motor peripheral neuropathy. In the last decade, he observed that his voice became laborious, leading to disartria and hypophonia. Otorhinolaryngological evaluation revealed vocal fold paresis, which was attributed to the neuromuscular disease after excluding acquired conditions. Brain and spinal cord MRI showed T2 hypersignal along the corticospinal tract. The SPG6 diagnosis was confirmed by an exome sequencing that identified a missense variant, (NM_144599.5:c.316G>A, p.Gly106Arg), within the microtubule binding site domain of the NIPA1 gene. This variant was classified as class 5 according to ACMG criteria, which implies it has known functional consequences. Sanger sequencing showed this variant was also present in his affected son.

Discussion: Mutations in the NIPA1 gene have been associated with autosomal dominant SPG6, which is a progressive neurodegenerative disorder. Although most cases present with a pure HSP phenotype, there has been some descriptions of complex cases, with variable clinical pictures. About 23% of all published cases report a complex phenotype, with epilepsy found in about 10% and a sensory and motor length-dependent peripheral neuropathy in only 5,5% of them. Disartria, hypophonia and a distal motor neuropathy have not been described, according to the best of our knowledge.

Final Comments: We presented an unusual case of SPG6 with a complex phenotype including epilepsy, axonal motor peripheral neuropathy, disartria and hypophonia in a patient harboring a pathogenic variant in NIPA1 gene, which expands the phenotypic spectrum of NIPA1-related disorders.