Molecular Genetics of Hereditary Sensory Neuropathies

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Neuromolecular Med. 2006 Mar;8(1-2):147-158. Related Articles, Links

Molecular Genetics of Hereditary Sensory Neuropathies.

Auer-Grumbach M, Mauko B, Auer-Grumbach P, Pieber TR.

Department of Internal Medicine, Medical Research Center, Medical

University of Graz, Stiftingtalstrabetae 24, A-8010 Graz, Austria.

Hereditary sensory neuropathies (HSN), also known as hereditary

sensory and autonomic neuropathies (HSAN), are a clinically and

genetically heterogeneous group of disorders. They are caused by

neuronal atrophy and degeneration, predominantly affecting peripheral

sensory and autonomic neurons. Both congenital and juvenile to

adulthood onset is possible.

Currently, the classification of the HSN depends on the mode of

inheritance, age at onset, and clinical presentation. Hallmark

features are progressive sensory loss, chronic skin ulcers, and other

skin abnormalities. Spontaneous fractures and neuropathic arthropathy

are frequent complications and often necessitate amputations.

Autonomic features vary between different subgroups.

Distal muscle weakness and wasting may be present and is sometimes so

prominent that it becomes difficult to distinguish HSN from Charcot-

Marie-Tooth syndrome.

Recent major advances in molecular genetics have led to the

identification of seven gene loci and six-disease causing genes for

autosomal-dominant and autosomal-recessive HSN. These genes have been

shown to play roles in lipid metabolism and the regulation of

intracellular vesicular transport, but also a presumptive

transcriptional regulator, a nerve growth factor receptor, and a

nerve growth factor have been described among the causative genes in

HSN.

Nevertheless, it remains unclear how mutations in the known genes

lead to the phenotype of HSN. In this review, we summarize the recent

progress of the molecular genetics of the HSN and the implicated

genes.