Clinical characteristics: Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease.
Diagnosis/testing: The diagnosis of HSAN2 is established in a proband with suggestive clinical and electrophysiologic findings and biallelic pathogenic variants in one of four genes: KIF1A, RETREG1 (FAM134B), SCN9A, or WNK1.
Management: Treatment of manifestations: Treatment is symptomatic and often involves a team including neurologists, orthopedic surgeons, and physiotherapists. Training in the care of the sensory-impaired limb, often in a diabetic foot care clinic, is important and includes self-examination – especially of the feet – for any signs of trauma. To prevent osteomyelitis, and hence the need for amputation, wounds require cleaning and protection along with antiseptic treatment. To prevent callous formation, the skin of neuropathic limbs requires hydration and lipid-based unguents. Appropriate shoes and socks are recommended.
Surveillance: The feet should be inspected daily for injuries or sources of wear. Annual follow up in centers with comprehensive care of diabetics and/or persons with Charcot-Marie-Tooth neuropathy is recommended.
Agents/circumstances to avoid: Ill-fitting shoes or other sources of trauma to the feet or hands (e.g., use protective gloves when handling hot items when cooking.)
Genetic counseling: HSAN2 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an HSAN2-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the HSAN2-causing pathogenic variants in the family are known, carrier testing of at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.
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