Rhizomelic chondrodysplasia punctata

Rhizomelic chondrodysplasia punctata (RCDP) is a rare, severe peroxisomal disorder characterized by disproportionate shortening of the proximal limb bones (rhizomelia), stippled calcifications in cartilage (chondrodysplasia punctata) visible on X-rays, cataracts, and profound growth and intellectual disability. The condition primarily affects the skeletal system, eyes, and central nervous system. There are several genetic subtypes: RCDP type 1 (the most common form, caused by mutations in the PEX7 gene), RCDP type 2 (caused by mutations in GNPAT), RCDP type 3 (caused by mutations in AGPS), RCDP type 4 (caused by mutations in FAR1), and RCDP type 5 (caused by mutations in PEX5). All subtypes result in impaired plasmalogen biosynthesis, a class of ether phospholipids essential for normal cell membrane function, particularly in the brain and other tissues. Affected infants typically present at birth or shortly after with severe shortening of the upper arms and thighs (rhizomelic limb shortening), bilateral cataracts, a flat facial appearance, microcephaly, joint contractures, ichthyosis (dry, scaly skin), and severe psychomotor delay. Seizures may also occur. Radiographic findings include stippled epiphyses, coronal clefting of vertebral bodies, and metaphyseal abnormalities. The severity can vary, with classic severe forms often leading to death in the first decade of life due to respiratory complications, while milder or nonclassic forms may have longer survival with less severe intellectual disability. There is currently no cure for RCDP. Treatment is supportive and multidisciplinary, focusing on management of cataracts (surgical removal), physical therapy for joint contractures, nutritional support, seizure management, and respiratory care. Orthopedic interventions may be considered for skeletal complications. Research into plasmalogen replacement therapy is ongoing but remains investigational. Early intervention programs and developmental support are important components of care.

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