Hereditary Motor and Sensory Neuropathy Type, CMT2, Seipin - BSCL2 (exon 3)

Klinische Symptomatik

Mutations in the Seipin gene cause a broad spectrum of disease phenotypes of hereditary neuropathy. Depending on how pronounced the symptoms, CMT/HMSN neuropathies, distal motor neuropathies (dHMN-V, dSMA-V) or Silver Syndrome (hereditary spastic paraparesis, SPG17) are initial clinical classifications.
Many patients display an asymmteric weakness and atrophy of the small hand muscles. This may be accompanied by foot deformities and gait disturbances due to atrophic pareses and / or spasticity of the lower extremities. Pyramidal signs and mild sensory impairment are also sometimes present. Initial symptoms most frequently affect the upper extremities and begin in a patient‘s childhood or teenage years. However, onset may also occur later, even with 50+ years. Electrophysiologcally, an axonal neuropathy indicated by reduced amplitudes and a normal to mildly reduced motor nerve conduction velocity, sometimes partial conduction blocks, is observed. Disease progression is very slow, the intrafamiliar variability is high.

Genetik

Hereditary neuropathies caused by mutations of the BSCL2 gene follow an autosomal dominant pattern of inheritance with incomplete penetrance. More than 20% of mutation carriers are not or only subclinically affected. The BSCL2 gene is located on chromosome 11 (11q13), consists of 24 exons and encodes the protein Seipin. Only two heterozygous missense mutations in exon 3 have been described (N88S and S90L); both affect a glycosilation site of Seipin. In contrast, the autosomal recessively inherited, congenital Berardinelli-Seip lipodystrophy is caused by distinct homo- or compound heterozygous mutations of BSCL2 .

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Diagnostik