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At a glance

An inherited syndrome characterized by a unilateral ichthyosiform erythroderma with strict midline demarcation sparing the face and ipsilateral defects involving all skeletal structures and internal organs. CHILD is an acronym that stands for Congenital Hemidysplasia with Ichthyosiform erythroderma, and Limb Defects.

Synonyms

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

History

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

Incidence

Approximately 60 cases have been reported.

Genetic inheritance

X-linked dominant trait with lethality in males. The responsible gene has been mapped to Xq28. CHILD Syndrome is caused by mutations in the NAD(P)H steroid dehydrogenase-like protein (NSDHL) gene that lead to inhibition of cholesterol synthesis and accumulation of toxic metabolic intermediates in affected tissues. This combination leads to defects in the lipid envelope of the stratum corneum of the skin and rendering it more permeable to water and ions, increasing its pH and activating proteases that degrade the integrity of the stratum corneum. More than 20 mutations causing CHILD Syndrome have been detected to date. Furthermore, skin fibroblasts from the affected areas 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). The 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.

Diagnosis

The hallmark of this syndrome is a unilateral, ichthyosiform erythroderma with sharp midline demarcation as a result of an inflammatory nevus. (Only a few cases with bilateral involvement have been described.) This nevus typically spares the face. Biochemically, the involved fibroblasts show peroxisomal deficiency. Molecular genetic testing will confirm the diagnosis.

Clinical aspects

The disorder usually is either congenital or has its onset with persisting ichthyosis within the first month of life clinically resembling psoriasiform epidermis. The histopathological examination of the involved epidermis is nonspecific and shows acanthosis, papillomatosis, and hyperkeratosis with parakeratosis. A particular skin lesion associated with CHILD Syndrome is the verruciform xanthoma that often presents as an exophytic, fleshy mass. Many paired organs are asymmetric due to the disease, with hypoplasia on the side of ichthyosis. The right side of the body is more often affected than the left side. Ipsilateral abnormalities on the side of ichthyosis are distinctive and affect the limbs (from hypoplasia of fingers to complete ...

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