HSAN2B is a neurodegenerative disorder of the peripheral nervous system. It is characterized by the impaired perception of pain, temperature and touch in the distal extremities, particularly in the lower limbs. Neuropathic skin causes hyperkeratosis and leads to ulcerations and infections. Patients suffer from osteomyelitis as well as acroosteolysis, and eventually the digits of the hands and feet undergo self-amputation. Autonomic disturbances include urinary incontinence, hyperhidrosis and tonic pupils.
The condition has an onset in the first or second decade of life, often before puberty. It is phenotypically variable, even between affected members of the same family. HSAN2B is a progressive disorder but there is limited information regarding its prognosis. Compared to other subsets of hereditary sensory and autonomic neuropathy 2, HSAN2B has been noted to have more severe autonomic dysfunction.
Diagnosis of the disorder is based on clinical findings, neurologic examinations, nerve conduction studies and genetic analysis of the FAM134B gene. There is currently no cure for the condition and treatment is focused on symptomatic care. Patients require a multi-disciplinary team of clinicians, surgeons and physical therapists to monitor their condition and prevent secondary complications.
The condition follows an autosomal recessive pattern of inheritance and is caused by mutations in the FAM134B gene. This gene encodes a receptor protein that is anchored to the endoplasmic reticulum. This receptor is responsible for autophagy of the endoplasmic reticulum by binding to the autophagy modifiers LC3 and GABARAP. It is believed that FAM134B may be required for the long-term survival of nociceptive and autonomic ganglion neurons. At least 5 different FAM134B gene mutations, including deletions and nonsense variants, have been implicated in Hereditary Sensory and Autonomic Neuropathy, type IIB.
Monies et al. (2017) analyzed the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 9-year-old male suffering from behavioral changes, muscle weakness, frequent falls and brisk reflexes was suspected to have hereditary spastic paraplegia. However, whole exome sequencing uncovered a homozygous mutation (c.694+2T>-) in exon 6 of the patient’s FAM134B gene, associated with Hereditary Sensory and Autonomic Neuropathy, Type 2B. Given the atypical presentation of the patient, this case helped in the phenotypic expansion of the disorder.
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