Distal Hereditary Motor Neuropathies, dHMN - HSPB8, HSBP3, GARS, DCTN1, SETX, BSCL2 (exon 3)

Clinical Features

Distal Hereditary Motor Neuropathies (dHMN) with degeneration of the second motor neuron are grouped with neuropathies. Due to the localization of the process, they are also referred to as the spinal form of Charcot-Marie-Tooth Syndrome. Congruent with the isolated affliction of the second motor neuron, affected patients normally show only distally localized motor loss.
dHMN Type 2 begins with paresis in the 20th to 40th year of life; type 5 manifests itself predominantly in the upper extremities.
ALS associated forms have also been described; dHMN caused by mutations in the SETX (Senataxin) gene are also referred to as ALS4 or juvenile ALS.
dHMN7B is caused by mutations in the DCTN1 gene (Dynactin 1); the symptoms are similar to ALS1. This HMN is often accompanied by vocal cord paresis.

Genetic Information

Distal hereditary motor neuropathies follow an autosomal dominant pattern of inheritance. The cause of the disease has been attributed to mutations in the HSPB8 (12q24), GARS (7p15), DCTN1 (2p13), SETX (9q34) and BSCL2 (Seipin, 11q13) genes. A spinocerebellar ataxia caused by mutations in the SETX gene (SCAR1; Ataxia Oculomotor Apraxie 2, AOA2) is an autosomal recessive inheritance; juvenile ALS4, however, is autosomal dominant.