Greenberg dysplasia

Greenberg dysplasia, also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia, is an extremely rare and lethal autosomal recessive skeletal disorder. It is caused by mutations in the LBR (lamin B receptor) gene, which encodes an enzyme involved in cholesterol biosynthesis (sterol-14-reductase). The disease is characterized by severe fetal hydrops (abnormal fluid accumulation in multiple body compartments), markedly disorganized skeletal development, and a distinctive "moth-eaten" radiographic appearance of the long bones due to ectopic calcification within cartilage. Other key features include severe shortening of the limbs (micromelia), platyspondyly (flattened vertebral bodies), and disorganized chondro-osseous development. Greenberg dysplasia presents prenatally and is invariably lethal, with affected fetuses typically dying in the second or third trimester of pregnancy or at birth. The condition affects the skeletal system profoundly, with abnormal endochondral ossification and widespread ectopic calcifications throughout the skeleton. Severe non-immune hydrops fetalis is a hallmark finding. The radiographic moth-eaten pattern of bones is a distinctive diagnostic feature that helps differentiate this condition from other lethal skeletal dysplasias. There is no treatment or cure for Greenberg dysplasia due to its uniformly lethal nature. Management is limited to supportive care and genetic counseling for affected families. Prenatal diagnosis may be possible through ultrasound findings of hydrops and skeletal abnormalities, and can be confirmed by molecular genetic testing of the LBR gene. Carrier testing and prenatal molecular diagnosis are available for families with a known pathogenic variant. Fewer than 30 cases have been reported in the medical literature.

Common questions about Greenberg dysplasia