HSPG2 related disorders
Schwartz-Jampel syndrome, type 1 (SJS1; MIM 255800) and dyssegmental dysplasia, Silverman-Handmaker type (DDSH; MIM 224410) are autosomal recessive disorders caused by mutations in the HSPG2 gene. This gene codes for perlecan, a basement membrane heparan sulfate proteoglycan.
Schwartz-Jampel syndrome, type 1 (SJS1) is a chondrodysplasia with associated myotonia. The disorder is characterized by postnatal short stature and dysmorphic fixed facies with pursed lips, bowed long bones, low set ears, blepharophimosis and spinal abnormalities that may include platyspondyly, coronal cleft vertebrae, kyphoscoliosis and lumbar lordosis. The metaphyses of long bones may be widened. The myotonia is progressive and it may be accompanied by muscular hypertrophy or weakness. Contractures of the hips, shoulders, wrists, fingers and toes may occur.
Dyssegmental dysplasia, Silverman-Handmaker type (DDSH) is a neonatal lethal skeletal dysplasia. Clinical findings include short, bowed long bones, small chest, anisospondyly, dyssegmental dysplasia, flat face with posteriorly rotated ears, micrognathia, cleft palate and reduced joint mobility. Patients may also have encephalocele, pulmonary hypoplasia and talipes equinovarus.
SJS1 and DDSH are allelic disorders. The differences in the severity of these two disorders are thought to be due to the complete lack of secreted functional perlecan in DDSH and secretion of some functional protein in SJS1.