AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome is a rare disorder characterized by birth defects of several organ systems, including the skin, the viscera, and the musculoskeletal and central nervous systems. In 1948, Zellweger and Uelinger reported a patient with a "half-sided osteochondrodermatitis and nevus ichthyosiformis." Since then, other patients with a similar constellation of defects have been described under a number of designations, including unilateral ichthyosiform erythroderma, unilateral erythrokeratoderma, unilateral epidermal nevus, unilateral ectromelia, inflammatory variable epidermal nevus, and unilateral limb and skin deformities with congenital heart disease. In 1980, Happle et al proposed the acronym CHILD for congenital hemidysplasia, ichthyosiform erythroderma, and limb defects.

Pathophysiology

Patients with CHILD syndrome have been found to have a mutation in the NSDHL gene encoding for an enzyme in the cholesterol biosynthetic pathway. The gene has been localized to Xq28 and encodes for 3beta-hydroxy sterol dehydrogenase involved in the oxidative decarboxylation of sterol C-4 methyl groups. Both heterozygous nonsense and heterozygous missense mutations have been identified. How this mutation causes the clinical findings in CHILD syndrome has yet to be elucidated. Studies have shown abnormalities of number and activity of peroxisomes in fibroblasts limited to areas of cutaneous involvement. Further studies suggest abnormalities in peroxisome number and activity that may be a result of increased levels of prostaglandins. The relationship between these findings and the cholesterol biosynthetic pathway is still under investigation.

Frequency

United States

No precise data are available regarding the frequency of the disease; however, fewer than 50 cases have been reported.

Mortality/Morbidity

Early death in persons with CHILD syndrome is most commonly due to cardiovascular malformations. However, central nervous system, skeletal, kidney, lung, and other visceral defects can cause significant problems.

Sex

Greater than two thirds of cases reported occur in females. An X-linked dominant mode of inheritance that is lethal to males has been proposed. A normal karyotype was demonstrated in a male patient with CHILD syndrome, suggesting an early postzygotic event.

Age

CHILD syndrome is a congenital disorder. The dermatosis may be present at birth or may develop during the first few weeks of life.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

CHILD syndrome is a congenital disorder.

Physical

• CHILD syndrome is a disorder with ipsilateral involvement of the skin, the viscera, and the musculoskeletal and central nervous systems.
• Cutaneous manifestations include unilateral, waxy, scaling, (ichthyosiform) erythematous plaques with a sharp midline demarcation present at birth or shortly thereafter and persistent throughout life. The distinct unilateral pattern may be diffuse and/or linear, with streaks following the lines of Blaschko. The face is usually spared. Right-sided involvement occurs at least twice as often as left-sided involvement. Small patches of involved skin can occur on the other side, and bilateral, symmetric involvement has been described. Ptychotropism, or body fold involvement, of the dermatosis is common. The most frequently affected areas are the vulva, axillae, and gluteal folds.
• The nails are often affected, and alopecia can occur on the affected side.
• Musculoskeletal abnormalities include ipsilateral limb reduction defects ranging from hypoplasia of the phalanges to defects of the long bones, including agenesis of an extremity. Ipsilateral hypoplasia of the axial skeleton, including the calvaria, mandible, scapula, ribs, and vertebrae, which can lead to scoliosis, can also be present. Epiphyseal stippling can be noted on radiographs in infants.
• Multiple ipsilateral anomalies of the viscera and central nervous system are observed in individuals with CHILD syndrome. These anomalies include cardiac malformations and ipsilateral hypoplasia of the brain, the lungs, the thyroid, and the reproductive tract. The ipsilateral kidney may also be involved. Cardiovascular malformations are the most common causes of early death and are encountered most often in left-sided cases.

Causes

CHILD syndrome is caused by an X-linked dominant mutation in the NSDHL gene encoding for an enzyme in the cholesterol biosynthetic pathway. The pathogenesis by which this mutation causes the clinical findings in individuals with CHILD syndrome is still under investigation.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

X-linked dominant chondrodysplasia puncta
Inflammatory linear verrucous epidermal nevus
Sebaceous nevus syndrome
Phacomatosis pigmentokeratotica

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Imaging Studies

• Radiographic examination of the head, the trunk, and the extremities is essential in detecting any skeletal abnormalities.
• Computed tomography of the head and the trunk may reveal hypoplasia or aplasia of the brain and/or the viscera.

Other Tests

• Definitive diagnosis can be made with genetic testing for mutations in the NSDHL gene.

Procedures

• Obtaining skin biopsy samples from involved and uninvolved skin areas is necessary.

Histologic Findings

The epidermis from involved skin shows marked acanthosis with alternating orthokeratosis and parakeratosis. Patchy hypergranulosis is also observed. A distinctive phenomenon of verruciform xanthoma, which is characterized by enlarged papillae filled with foamy histiocytes, has been reported when biopsy samples are obtained from body folds. Under electron microscopy, the parakeratotic corneocytes and basal cells contain lipid vacuoles and numerous intercellular vesicular structures. Abnormal cementosomes with electron-dense bodies have also been reported. The papillary dermis is thickened and filled with histiocytes containing large lipid vacuoles. The fibroblasts are similarly filled with lamellated structures.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

• Skin disease can be treated with topical or systemic retinoids. Surgical excision can also be an option in certain cases.
• Orthopedic abnormalities can be treated with braces or corrective surgery.
• Other medical care is dictated by the organ system(s) involved.

Consultations

Treatment of a patient with CHILD syndrome is multidisciplinary and dictated by the organ(s) involved.

• Consult a dermatologist for management of the cutaneous findings.
• Consult a pediatric orthopedic surgeon for evaluation and treatment of the musculoskeletal deformities.
• Consult a geneticist for counseling and for genetic testing.
• Consultation with a neurologist, cardiologist, or nephrologist may be needed depending on the organ system(s) involved.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Cutaneous findings are treated with systemic or topical steroids. Keratolytics have also been advocated.

Drug Category: Keratolytics

These agents are used for symptomatic relief of dry, scaling skin. They also help exfoliate the skin.

Drug Category: Retinoids

Topical and systemic retinoids have been advocated to help normalize the keratinization of the epidermis.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Complications

• Noncutaneous anomalies contribute to the most serious complications. Congenital cardiac defects are the main cause of early death in children. Other significant problems can occur with involvement of the musculoskeletal, renal, pulmonary, or central nervous systems.

Prognosis

• Patients with left-sided involvement have a worse prognosis.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol. Oct 1971;104(4):385-9. [Medline].
• Barr RJ, Plank CJ. Verruciform xanthoma of the skin. J Cutan Pathol. Dec 1980;7(6):422-8. [Medline].
• Cullen SI, Harris DE, Carter CH, Reed WB. Congenital unilateral ichthyosiform erythroderma. Arch Dermatol. Jun 1969;99(6):724-9. [Medline].
• Dale BA, Kimball JR, Fleckman P, et al. CHILD syndrome: lack of expression of epidermal differentiation markers in lesional ichthyotic skin. J Invest Dermatol. Apr 1992;98(4):442-9. [Medline].
• Diczfalusy U, Alexson SE. Peroxisomal chain-shortening of prostaglandin F2 alpha. J Lipid Res. Dec 1988;29(12):1629-36. [Medline].
• Emami S, Rizzo WB, Hanley KP, et al. Peroxisomal abnormality in fibroblasts from involved skin of CHILDsyndrome. Case study and review of peroxisomal disorders in relation toskin disease. Arch Dermatol. Sep 1992;128(9):1213-22. [Medline].
• Enjolras O, Guerin D, Hewitt J. [Knowledge of Solomon''s epidermal nevus syndrome (author''s transl)]. Ann Dermatol Venereol. Sep 1979;106(8-9):673-80. [Medline].
• Fink-Puches R, Soyer HP, Pierer G, et al. Systematized inflammatory epidermal nevus with symmetrical involvement: an unusual case of CHILD syndrome?. J Am Acad Dermatol. May 1997;36(5 Pt 2):823-6. [Medline].
• Goldyne ME, Williams ML. CHILD syndrome. Phenotypic dichotomy in eicosanoid metabolism andproliferative rates among cultured dermal fibroblasts. J Clin Invest. Jul 1989;84(1):357-60. [Medline].
• Golitz LE, Weston WL. Inflammatory linear verrucous epidermal nevus. Association with epidermal nevus syndrome. Arch Dermatol. Oct 1979;115(10):1208-9. [Medline].
• Happle R. X-linked dominant chondrodysplasia punctata. Review of literature and report of a case. Hum Genet. 1979;53(1):65-73. [Medline].
• Happle R, Koch H, Lenz W. The CHILD syndrome. Congenital hemidysplasia with ichthyosiformerythroderma and limb defects. Eur J Pediatr. Jun 1980;134(1):27-33. [Medline].
• Happle R, Mittag H, Kuster W. The CHILD nevus: a distinct skin disorder. Dermatology. 1995;191(3):210-6. [Medline].
• Happle R. The lines of Blaschko: a developmental pattern visualizing functional X-chromosome mosaicism. Curr Probl Dermatol. 1987;17:5-18. [Medline].
• Happle R. Ptychotropism as a cutaneous feature of the CHILD syndrome. J Am Acad Dermatol. Oct 1990;23(4 Pt 1):763-6. [Medline].
• Happle R. Child naevus is not ILVEN. J Med Genet. Mar 1991;28(3):214. [Medline].
• Happle R, Effendy I, Megahed M, et al. CHILD syndrome in a boy. Am J Med Genet. Mar 15 1996;62(2):192-4. [Medline].
• Hebert AA, Esterly NB, Holbrook KA, Hall JC. The CHILD syndrome. Histologic and ultrastructural studies. Arch Dermatol. Apr 1987;123(4):503-9. [Medline].
• Hummel M, Cunningham D, Mullett CJ, et al. Left-sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene. Am J Med Genet A. Oct 15 2003;122(3):246-51. [Medline].
• König A, Happle R, Fink-Puches R, et al. A novel missense mutation of NSDHL in an unusual case of CHILD syndrome showingbilateral, almost symmetric involvement. J Am Acad Dermatol. Apr 2002;46(4):594-6. [Medline].
• Rossman RE, Shapiro EM, Freeman RG. Unilateral ichthyosiform erythroderma. Arch Dermatol. Nov 1963;88:567-71. [Medline].
• Solomon LM, Fretzin DF, Dewald RL. The epidermal nevus syndrome. Arch Dermatol. Mar 1968;97(3):273-85. [Medline].
• Tadini G, Restano L, Gonzales-Perez R, et al. Phacomatosis pigmentokeratotica: report of new cases and further delineation of the syndrome. Arch Dermatol. Mar 1998;134(3):333-7. [Medline].
• Zellweger H, Uehlinger E. Ein Fall von halbseitiger Knochenchondromatose (Ollier) mit Naevus ichthyosiformis. Helv Paediatr Acta. 1948;2:153-163.

Article Last Updated: Jan 23, 2007