X-Linked dominant disorders of cholesterol biosynthesis in man and mouse

Malformation syndromes caused by disorders of cholesterol synthesis

“…302960) is a rare, X-linked, often male-lethal disorder associated with skin, skeletal, and ophthalmologic anomalies [for a recent review, see ( 18 )]. Asymmetry in the skeletal fi ndings and patterned skin lesions result from random X-inactivation in affected tissues in heterozygous females.…”

“…There is a characteristic craniofacial appearance with frontal bossing, midface hypoplasia, and a fl at nasal bridge. Postaxial polydactyly occurs in about 10% of reported cases and appears to be most common in this form of inherited CDP ( 18,233,234 ). Adult height is often reduced, averaging 60-63 inches in mildly affected females ( 235 ).…”

“…Unilateral, sharply demarcated, erythematous, ichthyosiform nevus, and ipsilateral limb reduction are characteristic fi ndings in CHILD Syndrome (E and F). The photographs in this fi gure were originally published in reference ( 18 ) and reproduced with permission from Elsevier Ltd.…”

Changes in gene expression associated with loss of function of the NSDHL sterol dehydrogenase in mouse embryonic fibroblasts

“…The gene was first identified by positional cloning in the mouse. Subsequently, mutations in human NSDHL were discovered in patients with congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome, an extremely rare X-linked, male-lethal malformation syndrome associated with unilateral ichthyosiform skin lesions and limb reduction defects (10,11).…”

Current Issues Regarding Prenatal Diagnosis of Inborn Errors of Cholesterol Biosynthesis

“…In both diseases affected females usually present at birth with skeletal and skin abnormalities [Herman et al, 2000]. In CDPX2 these include epiphyseal stippling and asymmetric rhizomelic shortening of the limbs, follicular atrophoderma, ichthyosiform erythroderma (following the Blaschko's lines), asymmetrical cataracts and accumulation in plasma and body tissues of cholesterol precursors: 8-dehydrocholesterol and cholest-8(9)-en-3-ol.…”