Expanded HSAN4 phenotype associated with two novel mutations in NTRK1

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Hereditary sensory and autonomic neuropathy type IV (HSAN4) is a severe autosomal recessive disorder.
• It is caused by mutations in the NTRK1 gene, encoding tyrosine kinase receptor A.
• Typical HSAN4 involves childhood onset of sensory/autonomic dysfunction, hyperthermia, infections, and cognitive impairment.

Observation:

• A rare, mild phenotype of HSAN4 is presented.
• This case involves a Swedish patient with adult-onset symptoms.
• The patient exhibits painful Charcot arthropathy, delayed wound healing, and mild polyneuropathy.

Findings:

• Two novel mutations in the NTRK1 gene were identified in the patient.
• The patient displays hypohidrosis but lacks significant autonomic dysfunction or cognitive impairment.
• This contrasts with the severe, childhood-onset phenotype typically associated with HSAN4.

Implications:

• These findings expand the known phenotypic spectrum of HSAN4.
• Novel NTRK1 mutations can result in milder, adult-onset disease.
• Understanding genotype-phenotype correlations in HSAN4 is crucial for diagnosis and management.