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Beradinelli-Seip-Congenital-Lipodystrophia - BSCL2

Clinical Features

Mutations in the BSCL2 gene can cause a wide variety of different forms of hereditary neuropathy. Depending on the prevailing symptoms, these could be CMT neuropathies, distal hereditary motor neuropathies (dHMN-V; dSMA-V), or Silver Syndrome (hereditary spastic paraparesis, SPG17).
Many patients exhibit asymmetrical weakness and atrophy of the small hand muscles, possibly accompanied by foot deformities and locomotive problems caused by distal atrophic paresis and/or a moderate spastic of the lower extremities. Pyramidal signs may be manifest; sensory impairment is, however, minor. The first symptoms-often occurring in the upper extremities-arise for the most part in a patient's 20s or 30s, but can also manifest much later, in some cases after age 50.

Electrophysical signs of axonal neuropathy are low amplitude, normal to slightly delayed motor nerve conduction velocity, and partial conduction block. The progression of the disease is usually slow; the intrafamilial variation as regards age of onset and clinical features is high. Since mutations are located in the BSCL2 gene, hereditary neuropathies are an autosomal dominant inheritance; because more than 20% of mutation carriers are unaffected or only subclinically affected, the mutations are considered to have reduced penetrance.

Genetic Information

The gene BSCL2 codes for the Seipin protein located on chromosome 11 (11q13) and consists of 24 exons. For patients with the symptoms described above, two heterozygote missense mutations in exon 2 of the BSCL2 gene have been described (N88S and S90L). Both mutations affect a glycolisation site in the Seipin protein. Other homo- or compound heterozygote BSCL2 mutations are associated with autosomal recessive congenital Berardinelli-Seip Lipodystrophy, which presents clinical features unrelated to hereditary neuropathy.

Diagnostic