RCDP1

RCDP1, or rhizomelic chondrodysplasia punctata type 1, is a rare autosomal recessive peroxisomal biogenesis disorder caused by pathogenic variants in PEX7, which encodes the peroxisomal targeting signal type 2 receptor. Defective PEX7 disrupts import of PTS2-containing enzymes into peroxisomes, leading to deficient plasmalogen synthesis and impaired peroxisomal lipid metabolism.

Clinical features typically appear in infancy and include rhizomelic shortening of the proximal limbs, characteristic facial features, cataracts, and growth and developmental delay. Skeletal abnormalities are prominent, with punctate epiphyseal calcifications visible on radiographs. Other manifestations may include hypotonia, feeding difficulties, seizures, hearing or vision impairment, and skeletal dysplasia.

Diagnosis is based on clinical and radiologic findings and is supported by biochemical tests showing reduced plasmalogens in erythrocyte membranes and elevated levels of certain branched-chain fatty acids such as phytanic and pristanic acids. Peroxisomal function tests and targeted sequencing of PEX7 confirm the diagnosis.

Differential diagnosis includes other types of rhizomelic chondrodysplasia punctata (RCDP2–6) caused by mutations in different genes, as well as Zellweger spectrum disorders. Management is multidisciplinary and supportive, addressing orthopedic, neurologic, ophthalmologic, and nutritional needs; there is no disease-specific cure. Genetic counseling is essential due to autosomal recessive inheritance, and prenatal testing is possible for at-risk families.

Prognosis varies, but is generally poor, with severe disease often presenting in infancy and substantial neurodevelopmental impairment; some individuals survive into childhood or beyond with varying levels of function.