Silver syndrome is a rare autosomal dominant neurodegenerative disorder 
characterized by marked amyotrophy and weakness of small hand muscles and 
spasticity in the lower limbs. The locus for Silver syndrome (SPG17) was 
assigned to a 13 cM region on chromosome 11q12-q14 in a single large pedigree. 
We recently found heterozygous mutations in the Berardinelli-Seip congenital 
lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor 
neuropathy type V (distal HMN V). Here we report the clinical features of two 
families with heterozygous BSCL2 mutations. Interestingly, both families show a 
clinical phenotype different from classical Silver syndrome, and in some 
patients the phenotype is also different from distal HMN V. Patients in the 
first family had marked spasticity in the lower limbs and very striking distal 
amyotrophy that always started in the legs. Patients in the second family had 
distal amyotrophy sometimes starting and predominating in the legs, but no 
pyramidal tract signs. These observations broaden the clinical phenotype of 
disorders associated with BSCL2 mutations, having consequences for molecular 
genetic testing.