Phenotypic and molecular characterization of a novel case of dyssegmental dysplasia, Silverman-Handmaker type.
Dyssegmental dysplasia, Silverman-Handmaker type (DDSH; #MIM 224410) is an autosomal recessive form of lethal dwarfism characterized by a defect in segmentation and fusion of vertebral bodies components ("anisospondyly") and by severe limb shortening. It is caused by mutations in the perlecan gene (HSPG2), but so far, only three molecularly confirmed cases have been reported. We report a novel case of DDSH in a fetus that presented at 15 weeks gestation with encephalocele, severe micromelic dwarfism and narrow thorax. After termination of pregnancy, radiographs showed short ribs, short and bent long bones and anisospondyly of two vertebral bodies. The fetus was homozygous for a previously undescribed null mutation in HSPG2.
Rieubland
Claudine
C
Division of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Claudine.Rieubland@insel.ch
Jacquemont
Sebastien
S
Mittaz
Laureane
L
Osterheld
Maria-Chiara
MC
Vial
Yvan
Y
Superti-Furga
Andrea
A
Unger
Sheila
S
Bonafé
Luisa
L
D000015:Abnormalities, Multiple / Q000235:genetics; D004392:Dwarfism / Q000235:genetics; D004677:Encephalocele / Q000235:genetics; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D006801:Humans; D008588:Meningocele / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics; D017354:Point Mutation; D011247:Pregnancy
D019812:Heparan Sulfate Proteoglycans; C071927:perlecan