What is HSN1?

The hereditary sensory neuropathies are a group of disorders caused by altered function in one or more elements of the peripheral nervous system. Hereditary sensory neuropathy type 1 (HSN1) is one particular subset that targets sensory nerve fibers and, to a lesser extent, some motor nerve fibers.

HSN1 typically begins in teenages or young adults, starting with subtle loss of sensation of pain and temperature in the feet. If sensory loss is severe, there may be recurrent infections, skin ulcers and bone infections, leading to amputation of the tips of some fingers and toes. Some individuals with HSN1 develop intense, lancinating pains. HSN1 progresses and is eventually associated with weakness. It runs in families, inherited as an autosomal dominant trait.

HSN1 was described for the first time in 1948. Because of its unique features the disorder was called "la maladie singuliere des os des pieds" or the singular disease of the bones of the feet. The disease was initially attributed to various causes including defects in the spinal cord. In 1951 it was concluded that the primary defect responsible of HSN1 resides in the sensory neurons and in the dorsal root ganglia.

Cases have been reported in different geographical populations and different ethnic groups. Sporadic cases of HSN1 have been also reported. There is no treatment for HSN1. However, the availability of accurate molecular diagnoses should improve the quality of life of HSN1 patients. Knowledge that an individual is at risk of developing HSN1 will allow use of protective measures to prevent injuries arising from early loss of pain and temperature sensation.

HSN1 Research Programs at the MGH

Dr. Brown and his staff have been investigating the genetic location of the HSN1 mutation for several years, pursuing an interest prompted by the privilege of meeting a family with HSN1 in the late 1970's.

He has been joined in the Day Laboratory's effort for the last several years by Dr. Khemissa Bejaoui. In two HSN1 families, the defective gene was linked to chromosome 9q22, confirming a linkage previously reported in Australian families of English descent. Recently Dr. Bejaoui identified, with collaborators, reported that HSN1 is caused by mutations in a gene called serine palmitoyl transferase that is important in the synthesis of some brain lipids.

Identification of the genetic defect allowed the postulation of hypotheses of the biochemical and pathological mechanisms that cause HSN-1.