OMIM ID:
Rhizomelic Chondrodysplasia Punctata
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Congenital cataracts are the outstanding ocular feature of this syndrome and are present in over 70% of patients. They are usually bilateral and symmetrical and may not be present for several months after birth.
Systemic Features
The name of this disorder comes from the punctate calcification seen in cartilage. The vertebrae have coronal clefting. The cartilage abnormalities result in defective bone growth with severe growth retardation, short stature, and joint contractures. Many infants die during the neonatal period and few survive beyond the first decade of life. However, milder forms have been reported. The skin can be ichthyotic and severe mental retardation is often accompanied by seizures. Red cells are deficient in plasmalogens while phytanic acid and very long chain fatty acids accumulate in the plasma, a biochemical profile characteristic of RCDP1.
Other types of chondrodysplasia punctata also exist (RCDP2 and RCDP3). The X-linked recessive (CDPX1; 302950), autosomal dominant tibia-metacarpal (118651), and humero-metacarpal types are not associated with cataracts.
A phenocopy sometimes results from maternal ingestion of dicoumarol in early pregnancy.
Genetics
Inheritance
This rare autosomal recessive condition results from mutations in the PEX7 gene (6q22-q24) causing a peroxisomal biogenesis disorder. Some clinical features overlap with those of Zellweger syndrome (214100) and infantile Refsum disease (266510), also peroxisomal biogenesis disorders.
Mutations in the same gene are responsible for adult Refsum disease-2 (266500). The latter, however, has other neurological symptoms as well as clinical features of retinitis pigmentosa with night blindness and restricted visual fields.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.