CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM NEVUS AND LIMB DEFECTS (CHILD) SYNDROME

NSDHL GENE ANALYSIS IN CHILD SYNDROME

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is an X linked dominant disorder with male lethality. The disorder is characterised by an inflammatory epidermal nevus with yellow scales showing a unique lateralisation pattern and strict midline demarcation. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life. Patients also have ipsilateral hypoplasia of the limbs ranging from metacarpal and phalanges shortening only to absence of an entire limb. Other features include unilateral hypoplasia or underdevelopment of the brain, heart defects (septal defects, unilateral ventricle), lung hypoplasia and kidneys defects (unilateral hydronephrosis, renal agenesis). Intellect is usually normal.

CHILD syndrome is caused by loss of function variants in the NSDHL gene. The NSDHL gene encodes a 3β-hydroxysteroid dehydrogenase which is involved in the cholesterol biosynthesis pathway (Konig et al. 2000 AJMG 90:339-346). Approximately 90% of NSDHL variants will be detected by sequence analysis and whole or partial gene deletions account for the remaining 10% (Bornholdt et al. 2005 J Med Genet 42,2:e17).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.