Rhizomelic Chondrodysplasia Punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, congenital contractures, characteristic ocular involvement, severe intellectual disability and spasticity. Characteristic facial features include broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears and micrognathia. RCDP presents in the neonatal period and most affected individuals die in the first decade of life, although milder forms of RCDP can present with variable growth and developmental delays and survival into adulthood.
Mutations in PEX7 [OMIM#601757] account for more than 90% of patients with RCDP1 [OMIM#215100].. The finding of a deficiency of plasmalogens in red blood cells, increased plasma concentration of phytanic acid, and normal plasma concentration of very long chain fatty acids is consistently identified in individuals with PEX7 mutations (1). PEX7 is one of sixteen PEX genes that are involved in mammalian peroxisome assembly.
Mutations in GNPAT [OMIM#222765] and AGPS [MIM#600121] account of less than 10% of patients with RCDP2 [OMIM#222765] and RCDP3 [OMIM#60012] respectively (2). PEX7 transports AGPS into the peroxisome, where AGPS and GNPAT partner on the luminal membrane surface.