[Hereditary sensory and autonomic neuropathy type IV]

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a very rare autosomal recessive neurological disorder caused by pathogenic variants in the NTRK1 gene. It is clinically characterized by insensitivity to pain, anhidrosis with recurrent febrile episodes, orthopedic complications secondary to repeated trauma, and, in some cases, intellectual disability. We report the case of a 43-year-old female patient with insensitivity to pain since the neonatal period, mild developmental delay, lingual self-mutilation, recurrent fever without infectious focus, Charcot-like joint deformities, and severe orthostatic hypotension. Neurological examination revealed generalized hypoalgesia and distal weakness in the lower limbs, corroborated by electrophysiological studies. Lumbar spine magnetic resonance demonstrated severe structural involvement, and Ewing's test documented both sympathetic and parasympathetic autonomic dysfunction. Genetic analysis identified the pathogenic NTRK1 variant (NM_002529.4): c.2311C>T; p.(Arg771Cys) in homozygosity, previously reported in individuals with CIPA. This finding was confirmed by intrafamilial segregation analysis, which demonstrated the homozygous status of the patient and heterozygous carrier status in her siblings. We present this case because of its rarity, its molecular confirmation, and its remarkable clinical manifestations, highlighting the importance of genetic diagnosis in rare neurological diseases.