Summary
Chondrodysplasia punctata is a group of diseases in which the common characteristic is bone calcifications near articulations from birth, along with other associated disorders such as limbs with short segments, facial dysmorphism with a hypoplastic nasal root, skin lesions, and cataract. Nonrhizomelic chondrodysplasia punctata is not an entity in itself but covers several diseases with variable modes of transmission. The overall prevalence of these diseases as a group is unknown. X-linked dominant chondrodysplasia punctata (or Conradi-Hünermann-Happle syndrome; see this term) is characterized by the association of asymmetrical limbs, lamellar ichthyosiform erythroderma and cataract that may be unilateral. Intelligence is normal. The disease predominantly affects females and is severe or even lethal in males. It is transmitted as an X-linked dominant trait and is caused by mutations in the EBP gene encoding an enzyme involved in cholesterol metabolism. Brachytelephalangic chondrodysplasia (see this term) associates severe facial dysmorphism (Binder's maxillonasal dysostosis; see this term), calcifications predominantly found in the tarsus and lower limbs, and hypoplastic distal phalanges. Stature and intelligence are normal to near-normal. The disorder is inherited as an X-linked recessive trait and is caused by a mutation in the ARSE gene. Other forms of non-rhizomelic chondrodysplasia punctata include chondrodysplasia punctata tibial-metacarpal type, Toriello-Higgins-Miller syndrome and chondrodysplasia punctata, Sheffield type (see these terms). Maternal intake of anticoagulants during pregnancy, deficiency of vitamin K-dependent coagulation factors and maternal vitamin K deficiency (see these terms) can cause symptoms that are very similar to those of brachytelephalangic chondrodysplasia punctata. Calcifications around the epiphyses may also be caused by fetal alcohol syndrome (see this term) and may be seen in fetuses born to mothers with disseminated lupus erythematosus (see this term). Chondrodysplasia punctata may be detected by ultrasound follow up, most often in the later stages of pregnancy, but identification of the exact form requires biochemical investigations (screening for abnormal sterols and long chain fatty acid analysis) of amniotic fluid samples. Treatment should be adapted depending on the form of chondrodysplasia punctata present. Prognosis is very variable. *Author: Prof. M. Le Merrer (November 2008)*.
