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.
Unilateral inflammatory nevus with hemidysplasia of the leg in a newborn
with CHILD Syndrome.
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
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 ...