Rhizomelic chondrodysplasia punctata type 1 (RCDP1) classic type, a peroxisome biogenesis disorder (PBD), is characterized by proximal shortening of the humerus and to a lesser degree the femur (rhizomelia), punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata, or CDP), coronal clefts of the vertebral bodies, and cataracts that are usually present at birth or appear in the first few months of life. Birth weight, length, and head circumference are often at the lower range of normal; postnatal growth deficiency is profound. Intellectual disability is severe, and the majority of children develop seizures. Most affected children do not survive the first decade of life; a proportion die in the neonatal period. A milder phenotype in which all affected individuals have congenital cataracts and chondrodysplasia is now recognized; some do not have rhizomelia, and some have less severe intellectual disability and growth deficiency.

The diagnosis of RCDP1 is based on clinical findings and confirmed by biochemical or molecular genetic testing. Biochemical tests of peroxisome function include: red blood cell concentration of plasmalogens (deficient), plasma concentration of phytanic acid (elevated), and plasma concentration of very long chain fatty acids (VLCFA) (normal), which has consistently predicted the PEX7 receptor defect in RCDP1. PEX7, which encodes the receptor for a subset of peroxisomal matrix enzymes, is the only gene in which pathogenic variants are known to cause RCDP1.

Treatment of manifestations: Management is supportive and limited by the multiple handicaps present at birth and poor outcome. Cataract extraction may restore some vision. Physical therapy is recommended to improve contractures; orthopedic procedures may improve function in some individuals.

Prevention of primary manifestations: Dietary restriction of phytanic acid to avoid the consequences of phytanic acid accumulation over time may benefit individuals with milder forms of RCDP.

Prevention of secondary manifestations: Poor feeding and recurrent aspiration may necessitate placement of a gastrostomy tube; attention to respiratory function with administration of influenza vaccine and RSV monoclonal antibody; docosohexanoic acid (DHA) supplementation in those who are deficient.

Surveillance: Monitoring of growth and development and regular assessments for seizure control, vision, hearing, contractures, and orthopedic complications.

RCDP1 is inherited in an autosomal recessive manner. At conception, each sib of a proband has a 25% chance of inheriting both pathogenic alleles and being affected, a 50% chance of inheriting one pathogenic allele and being an unaffected carrier, and a 25% chance of inheriting both normal alleles. Once the pathogenic variants have been identified in an affected family member, molecular genetic testing for carrier testing of at-risk relatives and prenatal testing for pregnancies at increased risk are possible. Prenatal diagnosis by assay of plasmalogen biosynthesis is possible for pregnancies at 25% risk for RCDP1.