Chondrodysplasia punctata represents clinically and genetically a heterogeneous group of disorders characterized by the presence of multiple congenital anomalies and
stippled epiphyses. We present
clinical course of the disease and the results of metabolic, X-ray and molecular analyses in 19-months old girl with
X-linked dominant chondrodysplasia punctata with
intrauterine growth retardation, craniofacial dysmorphy,
cataracts, cutaneous anomalies including
ichthyosis, asymmetric rhizomesomelic shortness of the limbs,
deformity of the spine, club foot,
polydactyly,
syndactyly, epiphyseal stippling and low
cholesterol (2.29 mmol/l). Spectrophotometric analysis revealed the presence of abnormal pattern of
cholesterol precursors in blood. The increased level of
8-dehydrocholesterol (42.2 micromol/l, controls < 1) and
7-dehydrocholesterol (25.5 micromol/l, controls < 1) recognised with GC/MS suggested an endogenous defect of
cholesterol biosynthesis. The diagnosis of
X-linked dominant chondrodysplasia punctata (CDPX2) was confirmed by the molecular analysis. Sequencing of the EBP gene encoding for 3beta-hydroxysteroid-delta8,delta7-isomerase revealed the presence of "de novo" heterozygous mutation c.327C>T (p.Arg110Stop). High
cholesterol diet normalized
cholesterol level (3.28 mmol/l) but it had no influence on the unfavourable prognosis of the disease. Low level of
cholesterol with abnormal
sterol profile in a child with congenital development anomalies represent an important
laboratory marker suggesting an inherited defect of
cholesterol biosynthesis.