Hereditary sensory and autonomic neuropathy type 1B

Hereditary sensory and autonomic neuropathy type 1B (HSAN1B) is an extremely rare autosomal dominant neurological disorder characterized by progressive degeneration of sensory and, to a lesser extent, autonomic neurons. It is caused by mutations in the DNMT1 gene (DNA methyltransferase 1), which plays a critical role in DNA methylation and gene regulation. HSAN1B is sometimes referred to as HSAN1 with dementia and hearing loss, reflecting its distinctive clinical features that distinguish it from other HSAN type 1 subtypes. The disease primarily affects the peripheral nervous system, leading to progressive sensory loss, particularly in the distal extremities (feet and hands). Loss of pain and temperature sensation can result in painless injuries, foot ulcers, and secondary infections that may lead to osteomyelitis and, in severe cases, amputations. A distinguishing feature of HSAN1B compared to other HSAN1 subtypes is the association with sensorineural hearing loss and progressive dementia, indicating central nervous system involvement. Autonomic dysfunction may also be present but is typically less prominent. Onset is generally in adulthood, typically in the second to fourth decades of life. The disease follows a progressive course. There is currently no cure or disease-modifying treatment for HSAN1B. Management is supportive and focuses on careful foot care and wound prevention, treatment of infections, hearing aids or cochlear implants for hearing loss, and neuropsychological support for cognitive decline. Genetic counseling is recommended for affected families given the autosomal dominant inheritance pattern.

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