eMedicine Specialties > Dermatology > Pediatric Diseases

CHILD Syndrome: Differential Diagnoses & Workup

Author: Neil Alan Fenske, MD, Chairman, Department of Dermatology and Cutaneous Surgery, Professor, Department of Dermatology and Cutaneous Surgery, Department of Pathology and Cell Biology, Department of Oncologic Sciences, University of South Florida College of Medicine
Coauthor(s): Elizabeth Arrington, MD, Resident Physician, Department of Dermatology, University of South Florida; Babak Roshdieh, MD, Consulting Staff, Department of Dermatology, Sierra View District Hospital; Richard (Rick) L Moore, MD, Staff Physician, Department of Dermatology and Cutaneous Surgery, University of South Florida
Contributor Information and Disclosures

Updated: Mar 10, 2009

Differential Diagnoses

Epidermal Nevus Syndrome

Other Problems to Be Considered

X-linked dominant chondrodysplasia puncta16
Inflammatory linear verrucous epidermal nevus17,18,19
Sebaceous nevus syndrome
Phacomatosis pigmentokeratotica20

Workup

Laboratory Studies

Laboratory testing involves sterol analysis of plasma, tissues, or cultured cells by gas chromatography–mass spectometry, which shows elevated levels of C4-methylated and C4-carboxy sterol intermediates.

Imaging Studies

Radiographic examination of the head, trunk, and extremities is essential for detecting any skeletal abnormalities. Additionally, computed tomography scanning 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 by DNA sequence analysis.

Procedures

A skin biopsy may be performed. Obtaining samples from both involved skin and uninvolved skin 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.21 Under electron microscopy, the parakeratotic corneocytes and basal cells contain lipid vacuoles and numerous intercellular vesicular structures.22 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.23,24,25

More on CHILD Syndrome

Overview: CHILD Syndrome
Differential Diagnoses & Workup: CHILD Syndrome
Treatment & Medication: CHILD Syndrome
Follow-up: CHILD Syndrome
References
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References

  1. Bittar M, Happle R. CHILD syndrome avant la lettre. J Am Acad Dermatol. Feb 2004;50(2 Suppl):S34-7. [Medline].

  2. Zellweger H, Uehlinger E. Ein Fall von halbseitiger knochenchondromatose (Ollier) mit naevus ichthyosiformis. Helv Paediatr Acta. May 1948;3(2):153-63. [Medline].

  3. Happle R, Koch H, Lenz W. The CHILD syndrome. Congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Eur J Pediatr. Jun 1980;134(1):27-33. [Medline].

  4. Hummel M, Cunningham D, Mullett CJ, Kelley RI, Herman GE. Left-sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene. Am J Med Genet A. Oct 15 2003;122A(3):246-51. [Medline].

  5. Konig A, Happle R, Fink-Puches R, Soyer HP, Bornholdt D, Engel H, et al. A novel missense mutation of NSDHL in an unusual case of CHILD syndrome showing bilateral, almost symmetric involvement. J Am Acad Dermatol. Apr 2002;46(4):594-6. [Medline].

  6. Konig A, Happle R, Bornholdt D, Engel H, Grzeschik KH. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet. Feb 14 2000;90(4):339-46. [Medline].

  7. Bornholdt D, Konig A, Happle R, et al. Mutational spectrum of NSDHL in CHILD syndrome. J Med Genet. Feb 2005;42(2):e17. [Medline].

  8. Happle R, Konig A, Grzeschik KH. Behold the CHILD, it's only one: CHILD syndrome is not caused by deficiency of 3 beta-hydroxysteroid-Delta 8, Delta 7-isomerase. Am J Med Genet. Oct 2 2000;94(4):341-3. [Medline].

  9. Kim CA, Konig A, Bertola DR, et al. CHILD syndrome caused by a deletion of exons 6-8 of the NSDHL gene. Dermatology. 2005;211(2):155-8. [Medline].

  10. Happle R, Effendy I, Megahed M, Orlow SJ, Küster W. CHILD syndrome in a boy. Am J Med Genet. Mar 15 1996;62(2):192-4. [Medline].

  11. Kaminska-Winciorek G, Brzezinska-Wcislo L, Jezela-Stanek A, Krajewska-Walasek M, Cunningham D, Herman GE. CHILD syndrome: clinical picture and diagnostic procedures. J Eur Acad Dermatol Venereol. May 2007;21(5):715-6. [Medline].

  12. Bittar M, Happle R, Grzeschik KH, et al. CHILD syndrome in 3 generations: the importance of mild or minimal skin lesions. Arch Dermatol. Mar 2006;142(3):348-51. [Medline].

  13. Happle R. The lines of Blaschko: a developmental pattern visualizing functional X-chromosome mosaicism. Curr Probl Dermatol. 1987;17:5-18. [Medline].

  14. Fink-Puches R, Soyer HP, Pierer G, Kerl H, Happle R. 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].

  15. Happle R. Ptychotropism as a cutaneous feature of the CHILD syndrome. J Am Acad Dermatol. Oct 1990;23(4 Pt 1):763-6. [Medline].

  16. Happle R. X-linked dominant chondrodysplasia punctata. Review of literature and report of a case. Hum Genet. 1979;53(1):65-73. [Medline].

  17. Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol. Oct 1971;104(4):385-9. [Medline].

  18. Golitz LE, Weston WL. Inflammatory linear verrucous epidermal nevus. Association with epidermal nevus syndrome. Arch Dermatol. Oct 1979;115(10):1208-9. [Medline].

  19. Happle R. Child naevus is not ILVEN. J Med Genet. Mar 1991;28(3):214. [Medline].

  20. 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].

  21. Barr RJ, Plank CJ. Verruciform xanthoma of the skin. J Cutan Pathol. Dec 1980;7(6):422-8. [Medline].

  22. Dale BA, Kimball JR, Fleckman P, Herbert AA, Holbrook KA. CHILD syndrome: lack of expression of epidermal differentiation markers in lesional ichthyotic skin. J Invest Dermatol. Apr 1992;98(4):442-9. [Medline].

  23. Emami S, Rizzo WB, Hanley KP, Taylor JM, Goldyne ME, Williams ML. Peroxisomal abnormality in fibroblasts from involved skin of CHILD syndrome. Case study and review of peroxisomal disorders in relation to skin disease. Arch Dermatol. Sep 1992;128(9):1213-22. [Medline].

  24. Goldyne ME, Williams ML. CHILD syndrome. Phenotypic dichotomy in eicosanoid metabolism and proliferative rates among cultured dermal fibroblasts. J Clin Invest. Jul 1989;84(1):357-60. [Medline].

  25. Hebert AA, Esterly NB, Holbrook KA, Hall JC. The CHILD syndrome. Histologic and ultrastructural studies. Arch Dermatol. Apr 1987;123(4):503-9. [Medline].

  26. Cullen SI, Harris DE, Carter CH, Reed WB. Congenital unilateral ichthyosiform erythroderma. Arch Dermatol. Jun 1969;99(6):724-9. [Medline].

  27. Diczfalusy U, Alexson SE. Peroxisomal chain-shortening of prostaglandin F2 alpha. J Lipid Res. Dec 1988;29(12):1629-36. [Medline].

  28. 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].

  29. Happle R, Mittag H, Küster W. The CHILD nevus: a distinct skin disorder. Dermatology. 1995;191(3):210-6. [Medline].

  30. Rossman RE, Shapiro EM, Freeman RG. Unilateral ichthyosiform erythroderma. Arch Dermatol. Nov 1963;88:567-71. [Medline].

  31. Solomon LM, Fretzin DF, Dewald RL. The epidermal nevus syndrome. Arch Dermatol. Mar 1968;97(3):273-85. [Medline].

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Further Reading

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Keywords

CHILD syndrome, congenital hemidysplasia, ichthyosiform nevus, limb defects, unilateral ichthyosiform erythroderma, unilateral erythrokeratoderma, unilateral epidermal nevus, unilateral ectromelia, inflammatory variable epidermal nevus, unilateral limb and skin deformities with congenital heart disease, CHILD nevus, congenital hemidysplasia with ichthyosiform erythroderma and limb defects

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Contributor Information and Disclosures

Author

Neil Alan Fenske, MD, Chairman, Department of Dermatology and Cutaneous Surgery, Professor, Department of Dermatology and Cutaneous Surgery, Department of Pathology and Cell Biology, Department of Oncologic Sciences, University of South Florida College of Medicine
Disclosure: Dermik Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; Graceway Pharmaceuticals Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Warner Chilcott Honoraria Speaking and teaching

Coauthor(s)

Elizabeth Arrington, MD, Resident Physician, Department of Dermatology, University of South Florida
Elizabeth Arrington, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.

Babak Roshdieh, MD, Consulting Staff, Department of Dermatology, Sierra View District Hospital
Disclosure: Nothing to disclose.

Richard (Rick) L Moore, MD, Staff Physician, Department of Dermatology and Cutaneous Surgery, University of South Florida
Richard (Rick) L Moore, MD is a member of the following medical societies: American Academy of Dermatology and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Abdul-Ghani Kibbi, MD, Chairman and Professor, Department of Dermatology, American University of Beirut Medical Center, Lebanon
Disclosure: none None None

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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