The phenotype of motor neuropathies associated with BSCL2 mutations is broader than Silver syndrome and distal HMN type V.
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.
Irobi
Joy
J
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
Van den Bergh
Peter
P
Merlini
Luciano
L
Verellen
Christine
C
Van Maldergem
Lionel
L
Dierick
Ines
I
Verpoorten
Nathalie
N
Jordanova
Albena
A
Windpassinger
Christian
C
De Vriendt
Els
E
Van Gerwen
Veerle
V
Auer-Grumbach
Michaela
M
Wagner
Klaus
K
Timmerman
Vincent
V
De Jonghe
Peter
P
D000293:Adolescent; D000328:Adult; D002648:Child; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D018740:Genetic Heterogeneity; D006225:Hand; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D007866:Leg; D008875:Middle Aged; D009128:Muscle Spasticity / Q000235:genetics; D018908:Muscle Weakness / Q000235:genetics; D009133:Muscular Atrophy / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics; D013577:Syndrome
C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits