Heterozygous variants in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene are a common cause of distal hereditary motor neuropathy (dHMN) with frequent intrinsic hand muscle-predominant involvement (dHMN-V). In several cases, spasticity may be associated to this dHMN, known as the Silver syndrome or Spastic Paraplegia type 17 (SPG17). Nerve conduction studies frequently show a predominant axonal motor neuronopathy and the disease is usually slowly progressive.
BSCL2-related HMN are inherited in an autosomal dominant manner and the diagnosis can be stablished in a patient with a characteristic clinical and electrophysiologic phenotype in whom a heterozygous BSCL2 pathogenic variant is identified on molecular genetic testing. The p.Asn88Ser and p.Ser90Leu mutations account for the majority of BSCL2 patients, whilst the p.Ser90Trp and p.Arg96His mutations have been less frequently documented.
Biallelic variants in this same gene cause an autosomal recessive congenital generalized lipodystrophy (type 2) in children.
BSCL2