Dyssegmental dysplasia, Silverman-Handmaker type

Dyssegmental dysplasia, Silverman-Handmaker type (DDSH) is a rare, severe, and typically lethal skeletal dysplasia characterized by profound abnormalities in skeletal development, particularly affecting the vertebral column and long bones. It is caused by homozygous or compound heterozygous mutations in the HSPG2 gene, which encodes perlecan, a major heparan sulfate proteoglycan of basement membranes and cartilage. The disorder is also known as dyssegmental dwarfism, Silverman-Handmaker type, or dyssegmental dysplasia with glaucoma. Clinical features are apparent at birth and include severe short-limbed dwarfism, marked micromelia, a narrow thorax, and distinctive vertebral anomalies with irregular and disorganized vertebral body ossification (anisospondyly). Affected infants typically have a flat face, micrognathia, cleft palate, and encephalocele or occipital skull defects. Additional findings may include congenital glaucoma, joint contractures, and reduced joint mobility. The long bones are short and broad with irregular metaphyses. Internal organ abnormalities may also be present. The prognosis for DDSH is very poor, with most affected individuals dying in the neonatal period or early infancy due to respiratory insufficiency related to the severely narrow thorax and pulmonary hypoplasia. There is no specific curative treatment; management is supportive and palliative. Genetic counseling is important for affected families, as the condition follows autosomal recessive inheritance. Prenatal diagnosis may be possible through molecular testing or ultrasonographic detection of skeletal abnormalities.

Common questions about Dyssegmental dysplasia, Silverman-Handmaker type