Chondrodysplasia Punctata

Definition

The term chondrodysplasia punctata describes a group of osteochondrodysplasias characterized by punctate calcifications in cartilage, depending on the type and genetic alterations, and other organ system abnormalities.

Prevalence and Epidemiology

The heterogeneous bone dysplasias comprising chondrodysplasia punctata occur with an incidence of approximately 1 : 100,000 live births. The exact incidence for the specific types is unknown.

Etiology, Pathophysiology, and Embryology

There are six main types of chondrodysplasia punctata:

• rhizomelic form types 1, 2, and 3 (autosomal recessive)

• Conradi-Hünermann syndrome 2 (X-linked dominant) (CDPX2)

• brachytelephalangic (X-linked recessive) (CDXP1)

• autosomal dominant type (autosomal dominant)

Rhizomelic chondrodysplasia punctata, usually lethal by 2 years of age, is a rare autosomal recessive disorder of peroxisome metabolism. It is characterized by rhizomelic shortening of the long bones (humeri and femora) and punctate calcifications of the cartilaginous portions of skeleton, particularly the proximal humeri and femora. Rhizomelic chondrodysplasia punctata can be subclassified into three types based on locus heterogeneity, although all are recessively inherited and result from homozygous or compound heterozygous mutations. Type 1 results from mutations in the PEX7 gene that encodes peroxin 7. Type 2 results from mutations in the acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) gene, and type 3 results from mutations in the alkyl-dihydroxyacetonephosphate synthase (ADAPS) gene.

Conradi-Hünermann syndrome is an X-linked dominant form that is due to a deficiency of delta(8)-delta(7) sterol isomerase emopamil-binding protein. This form is probably lethal in the hemizygous state in affected males. Affected females have elevated serum levels of 8(9)-cholesterol and 8-dehydrocholesterol. The brachytelephalangic type of chondrodysplasia punctata (CDXP1) results from mutations in the gene that encodes arylsulfatase E. In the autosomal dominant type of chondrodysplasia punctata and the very similar tibia-metacarpal type, the molecular defect has not yet been defined.