Hereditary sensory neuropathies (mentions CMT types) Austrian Research

[Guest guest]

Research Abstract from Drugs Today (Barc). 2004 May;40(5):385-94.

Hereditary sensory neuropathies.

Auer Grumbach M.

Institute of Medical Biology and Human Genetics, Medical University

Graz, Graz, Austria.

Hereditary sensory neuropathies (HSNs) are a group of genetically

determined peripheral neuropathies with prominent disturbance of the

peripheral sensory neurons. They are characterized by sensory loss,

insensitivity to pain, a variable degree of muscle weakness and wasting,

as well as autonomic features. Frequent complications are foot

ulcerations and infections that may lead to osteomyelitis, followed by

necrosis and amputations. Consequently, the hereditary sensory

neuropathies have also been termed ulceromutilating neuropathies. On the

other hand, in the presence of additional motor weakness, they have been

subclassified among the group of Charcot-Marie-Tooth (CMT) disorders.

Sporadic and familial cases with different modes of inheritance are

known to affect both children and adults. The most prevalent forms of

the autosomal dominantly inherited hereditary sensory neuropathies are

HSN I and CMT 2b. HSN I is associated with mutations in the SPTLC1 gene,

whereas mutations in the RAB7 gene have been identified in CMT 2b.

However, at least one more hitherto unknown gene responsible for

autosomal-dominant hereditary sensory neuropathies must exist.

Autosomal-recessive hereditary sensory neuropathies types III and IV,

and probably also type V, result from mutations in the IKBKAP and NTRK1

genes. Very recently, the gene in HSN II (HSN2) has been identified. A

spontaneous autosomal-recessive mutation in the Cct4 gene has been

reported in the Sprague-Dawley rat strain with early onset sensory

neuropathy. Although no curative treatment is available so far, and

current therapy is limited to symptom relief, these molecular genetic

advances in knowledge about the hereditary sensory neuropathies can be

translated into clinical practice by improving diagnosis and genetic

counseling. They will also be the basis for functional studies in the

future.