What Is HSAN-4?
HSAN-4 is a type of CMT caused by autosomal recessive mutations in the NTRK1 gene. This gene provides instructions for making the high-affinity nerve growth factor receptor TrkA, which is essential for the development and survival of pain- and temperature-sensing nerve cells. Mutations in the NTRK1 gene disrupt this function, leading to impaired nerve signal transmission.
HSAN-4 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
Symptoms of HSAN-4 are present from birth and center on a congenital inability to sense pain together with an inability to sweat. This subtype affects the small sensory and autonomic nerve fibers. Nerve conduction of the large fibers may be relatively preserved, reflecting the axonal and small-fiber nature of the disease.
HSAN-4 symptoms may include:
- Congenital insensitivity to pain
- Inability to sweat (anhidrosis)
- Recurrent episodes of unexplained fever
- Reduced temperature sensation
- Repeated injuries that go unnoticed due to absent pain
- Cognitive impairment in some individuals
- Foot drop
- Additional symptoms not listed here
Disease Course
HSAN-4 is present from birth and carries serious risks, particularly in early childhood. Recurrent episodes of high fever from the inability to sweat can be life-threatening in infancy, and the absence of pain sensation leads to repeated unrecognized injuries. With careful management of temperature regulation and injury prevention, individuals can survive into adulthood, though the disease course remains variable.
