CHILD Syndrome

An inherited syndrome characterized by unilateral inflammatory nevus with strict midline demarcation sparing the face and ipsilateral defects involving all skeletal structures and internal organs. CHILD is an acronym for congenital hemidysplasia with ichthyosiform erythroderma and limb defects.

(Figure)

Unilateral Erythrokeratoderma; Unilateral Ectromelia; Unilateral Ichthyosiform Erythroderma; Unilateral Ichthyosiform Erythroderma with Ipsilateral Malformations.

Although Otto Sachs was the first to describe this disorder in an 8-year-old girl in 1903, R. Happle and colleagues were the first to use the acronymic designation “CHILD syndrome” in 1980.

Approximately 30 cases have been reported.

X-linked dominant trait with lethality in males. The responsible gene has been mapped to Xq28.

In view of the pattern of lateralization of the lesions, a postzygotic mutation appears to be more likely than a gametic half-chromatid mutation. It probably is caused by mutations in the NAD(P)H steroid dehydrogenase-like protein gene (NSDHL) and in the emopamil-binding protein gene (EBP), which is needed for cholesterol synthesis. Furthermore, skin fibroblasts from the affected area not only show a slower growth rate, but also a numerical and functional decrease in peroxisomes. This peroxisomal defect is limited to affected skin areas (peroxisomes in fibroblasts from unaffected skin are normal in number and function). This difference in growth rate seems to be associated with increased prostaglandin E2 levels in affected skin areas because peroxisomes are involved in the metabolism of prostaglandins and fibroblast growth can be accelerated in vitro with prostaglandin synthesis inhibitors.

The hallmark of this syndrome is a sharp midline demarcation of a unilateral, ichthyosiform erythroderma as a result of an inflammatory nevus. (Only one case with bilateral involvement has been described.) This nevus spares the face. Many organs are asymmetrical, with hypoplasia on the side of ichthyosis. The right side of the body is more often affected than the left side. Histopathology of the involved epidermis is nonspecific and shows acanthosis, papillomatosis, and hyperkeratosis with parakeratosis. Biochemically, the involved fibroblasts show peroxisomal deficiency.

The disorder usually is either congenital or has its onset with persisting ichthyosis within the first month of life. Ipsilateral abnormalities on the side of ichthyosis are distinctive and affect the limbs (from hypoplasia of fingers to complete agenesis of the entire limb, onychodysplasia, webbing of elbows and knees), the bones (hypoplasia of skull, mandible, vertebrae, clavicles, ribs, scapulae), the central nervous system (mild mental retardation, ipsilateral brain hypoplasia, including brainstem, and cranial nerve anomalies), the heart (atrial and ventricular septal defects, single ventricle, single coronary ostium), the lungs (lung hypoplasia), and the kidneys (unilateral renal agenesis). Thyroid, adrenal, and genitourinary abnormalities and myelomeningocele have been described. Death most often results from cardiac lesions. ...