A Novel Homozygous Pathogenic Variant in SCN9A Gene Causing Hereditary Sensory and Autonomic Neuropathy Type ID: A Case Report

Abstract Hereditary Sensory and Autonomic Neuropathy type ID (HSAN ID), caused by mutations in the SCN9A gene, is an exceptionally rare inherited disorder characterized by a profound absence of pain perception and varying degrees of autonomic dysfunction. We present the case of a female patient, currently in her early school-age years, born to consanguineous parents, who exhibited congenital insensitivity to pain and severe anhidrosis since infancy. Clinical presentation included recurrent unexplained injuries, oral self-mutilation, and frequent, unnoticed infections, leading to severe complications like left lung empyema requiring Video-Assisted Thoracoscopic Surgery (VATS) Decortication. Genetic testing via Whole Exome Sequencing identified a novel homozygous nonsense variant (c.901A > T, p.K301*) in the SCN9A gene, confirming the diagnosis and classifying it as pathogenic according to ACMG guidelines. This variant leads to a truncated, non-functional Nav1.7 channel protein, explaining the sensory deficits. This case highlights the challenges in diagnosing and managing such rare conditions, emphasizing the critical role of early genetic identification and a proactive multidisciplinary approach to prevent severe morbidity and improve long-term outcomes. Furthermore, the severe anhidrosis observed in this SCN9A-related case suggests a potentially broader involvement of Nav1.7 in autonomic functions than traditionally recognized.