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. No effective treatment for the dermatosis is known. Orthopedic (scoliosis), plastic, or prosthetic surgery may be required for specific anomalies. The prognosis depends on the presence and severity of internal and skeletal defects.

A detailed review of all body systems is necessary because the disease is multisystemic. In particular, a systematic review of associated cardiovascular, respiratory, and neurologic disease is mandatory. Examination of the cardiovascular system for the presence, type, and severity of cardiac malformations may require electrocardiography, echocardiography, and cardiac catheterization. If scoliosis or unilateral lung hypoplasia is present, a detailed respiratory evaluation is necessary (i.e., chest radiograph, arterial blood gas analysis, pulmonary function tests). If mandibular hypoplasia is present, the airway should be assessed for potential difficulties with tracheal intubation. Laboratory investigations should include a complete blood count and serum concentrations of electrolytes, urea, creatinine, and thyroid hormones.

Anesthesia in these patients has not been reported. A regional anesthesia technique is recommended whenever possible. However, the performance of a central neuraxial block may be technically challenging in view of the abnormal vertebrae. Severe scoliosis can hinder proper positioning, and careful padding is necessary. Induction and maintenance of general anesthesia will be dictated by the presence, type, and severity of cardiac defects and the degree of pulmonary hypoplasia. Postoperative ventilation may be necessary if a high-dose narcotic technique was used for induction and maintenance of anesthesia (secondary to cardiac defects) or when significant respiratory impairment is present. Positive ventilation with the lowest peak airway pressure should be used in the presence of pulmonary hypoplasia to prevent barotrauma to the lungs. Both peripheral and central venous access can be difficult because of limb and/or clavicular anomalies.

Subacute bacterial endocarditis prophylaxis may be required. If tracheal intubation is anticipated to be difficult in the presence of a hypoplastic mandible, muscle relaxants should not be used until the airway has been secured. Anesthetic drugs and perioperative fluid regimen should be adapted to renal function. Avoid heavy sedative premedication in the presence of significant respiratory impairment.