title: The phenotype of motor neuropathies associated with BSCL2 mutations is broader than Silver syndrome and distal HMN type V.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
authors.forename: Joy
authors.initials: J
authors.lastname: Irobi
authors.forename: Peter
authors.initials: P
authors.lastname: Van den Bergh
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen
authors.forename: Lionel
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: Ines
authors.initials: I
authors.lastname: Dierick
authors.forename: Nathalie
authors.initials: N
authors.lastname: Verpoorten
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
authors.forename: Els
authors.initials: E
authors.lastname: De Vriendt
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Gerwen
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
mesh_terms: 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
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits