Hereditary sensory neuropathy type I (HSN I) is a slowly progressive
neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal
muscle weakness and wasting, and chronic
skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are
spontaneous fractures,
osteomyelitis and
necrosis, as well as neuropathic
arthropathy which may even necessitate
amputations. Some patients suffer from severe
pain attacks. Hypacusis or
deafness, or
cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone
infections or
necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other
hereditary sensory and autonomic neuropathies (
HSAN), especially
HSAN II, as well as
diabetic foot syndrome,
alcoholic neuropathy, neuropathies caused by other
neurotoxins/drugs, immune mediated neuropathy,
amyloidosis,
spinal cord diseases,
tabes dorsalis, lepra neuropathy, or decaying skin tumours like
amelanotic melanoma. Management of HSN I follows the guidelines given for
diabetic foot care (removal of pressure to the
ulcer and eradication of
infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease.