Sections

CHILD Syndrome

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.

Plasma cholesterol is normal in patients with CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome.

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

Ultrasonography of the viscera, echocardiography, and full brain magnetic resonance imaging help identify internal anomalies associated with CHILD syndrome.^[34]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 and papillomatosis with alternating orthokeratosis and parakeratosis. Patchy hypergranulosis and a superficial perivascular infiltrate are also observed.^{[35, 36]}

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.^{[37, 38]}Under electron microscopy, the parakeratotic corneocytes and basal cells contain lipid vacuoles and numerous intercellular vesicular structures.^[39]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.^{[35, 40, 41]}

Treatment & Management

Bittar M, Happle R. CHILD syndrome avant la lettre. J Am Acad Dermatol. 2004 Feb. 50(2 Suppl):S34-7. [QxMD MEDLINE Link].
Zellweger H, Uehlinger E. Ein Fall von halbseitiger knochenchondromatose (Ollier) mit naevus ichthyosiformis. Helv Paediatr Acta. 1948 May. 3(2):153-63. [QxMD MEDLINE Link].
Happle R, Koch H, Lenz W. The CHILD syndrome. Congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Eur J Pediatr. 1980 Jun. 134(1):27-33. [QxMD MEDLINE Link].
Knape RM, Gandhi KB, Tuli SY, Khuddus N. Optic Nerve Findings in CHILD Syndrome. J Pediatr Ophthalmol Strabismus. 2010 Sep 22. 47 Online:e1-3. [QxMD MEDLINE Link].
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. 2003 Oct 15. 122A(3):246-51. [QxMD MEDLINE Link].
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. 2002 Apr. 46(4):594-6. [QxMD MEDLINE Link].
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. 2000 Feb 14. 90(4):339-46. [QxMD MEDLINE Link].
Mi XB, Luo MX, Guo LL, Zhang TD, Qiu XW. CHILD Syndrome: Case Report of a Chinese Patient and Literature Review of the NAD[P]H Steroid Dehydrogenase-Like Protein Gene Mutation. Pediatr Dermatol. 2015 Nov-Dec. 32 (6):e277-82. [QxMD MEDLINE Link].
Bergqvist C, Abdallah B, Hasbani DJ, Abbas O, Kibbi AG, Hamie L, et al. CHILD syndrome: A modified pathogenesis-targeted therapeutic approach. Am J Med Genet A. 2018 Mar. 176 (3):733-738. [QxMD MEDLINE Link].
Bornholdt D, Konig A, Happle R, et al. Mutational spectrum of NSDHL in CHILD syndrome. J Med Genet. 2005 Feb. 42(2):e17. [QxMD MEDLINE Link].
CHILD syndrome. National Institute of Health: Genetic and Rare Diseases Information Center. Available at https://rarediseases.info.nih.gov/diseases/6039/child-syndrome. April 19, 2019; Accessed: July 30, 2019.
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. 2000 Oct 2. 94(4):341-3. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Farese RV Jr, Herz J. Cholesterol metabolism and embryogenesis. Trends Genet. 1998 Mar. 14(3):115-20. [QxMD MEDLINE Link].
Johnson RL, Scott MP. New players and puzzles in the Hedgehog signaling pathway. Curr Opin Genet Dev. 1998 Aug. 8(4):450-6. [QxMD MEDLINE Link].
Porter FD, Herman GE. Malformation syndromes caused by disorders of cholesterol synthesis. J Lipid Res. 2011 Jan. 52(1):6-34. [QxMD MEDLINE Link]. [Full Text].
Seeger MA, Paller AS. The role of abnormalities in the distal pathway of cholesterol synthesis in the Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) syndrome. Biochim Biophys Acta. 2014 Mar. 1841(3):345-52. [QxMD MEDLINE Link].
Happle R, Effendy I, Megahed M, Orlow SJ, Küster W. CHILD syndrome in a boy. Am J Med Genet. 1996 Mar 15. 62(2):192-4. [QxMD MEDLINE Link].
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. 2007 May. 21(5):715-6. [QxMD MEDLINE Link].
Bittar M, Happle R, Grzeschik KH, et al. CHILD syndrome in 3 generations: the importance of mild or minimal skin lesions. Arch Dermatol. 2006 Mar. 142(3):348-51. [QxMD MEDLINE Link].
Happle R. The lines of Blaschko: a developmental pattern visualizing functional X-chromosome mosaicism. Curr Probl Dermatol. 1987. 17:5-18. [QxMD MEDLINE Link].
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. 1997 May. 36(5 Pt 2):823-6. [QxMD MEDLINE Link].
Happle R. Ptychotropism as a cutaneous feature of the CHILD syndrome. J Am Acad Dermatol. 1990 Oct. 23(4 Pt 1):763-6. [QxMD MEDLINE Link].
Stiff KM, Cohen PR. Vegas (Verruciform Genital-Associated) Xanthoma: A Comprehensive Literature Review. Dermatol Ther (Heidelb). 2017 Mar. 7 (1):65-79. [QxMD MEDLINE Link].
Blankenship DW, Zech L, Mirzabeigi M, Venna S. Verruciform xanthoma of the upper-extremity in the absence of chronic skin disease or syndrome: a case report and review of the literature. J Cutan Pathol. 2013 Aug. 40(8):745-52. [QxMD MEDLINE Link].
Avgerinou GP, Asvesti AP, Katsambas AD, et al. CHILD syndrome: the NSDHL gene and its role in CHILD syndrome, a rare hereditary disorder. J Eur Acad Dermatol Venereol. 2010 Jun. 24(6):733-6. [QxMD MEDLINE Link].
Chander R, Varghese B, Jabeen M, Garg T, Jain M. CHILD syndrome with thrombocytosis and congenital dislocation of hip: A case report from India. Dermatol Online J. 2010 Aug 15. 16(8):6. [QxMD MEDLINE Link].
Happle R. X-linked dominant chondrodysplasia punctata. Review of literature and report of a case. Hum Genet. 1979. 53(1):65-73. [QxMD MEDLINE Link].
Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol. 1971 Oct. 104(4):385-9. [QxMD MEDLINE Link].
Golitz LE, Weston WL. Inflammatory linear verrucous epidermal nevus. Association with epidermal nevus syndrome. Arch Dermatol. 1979 Oct. 115(10):1208-9. [QxMD MEDLINE Link].
Happle R. Child naevus is not ILVEN. J Med Genet. 1991 Mar. 28(3):214. [QxMD MEDLINE Link].
Tadini G, Restano L, Gonzales-Perez R, et al. Phacomatosis pigmentokeratotica: report of new cases and further delineation of the syndrome. Arch Dermatol. 1998 Mar. 134(3):333-7. [QxMD MEDLINE Link].
Asch S, Sugarman JL. Epidermal nevus syndromes: New insights into whorls and swirls. Pediatr Dermatol. 2018 Jan. 35 (1):21-29. [QxMD MEDLINE Link].
Souich C, Raymond FL, Grzeschik KH, Boerkoel CF. NSDHL-Related Disorders. Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews. Seattle, Wash: University of Washington; 1993-2019.
Hebert AA, Esterly NB, Holbrook KA, Hall JC. The CHILD syndrome. Histologic and ultrastructural studies. Arch Dermatol. 1987 Apr. 123(4):503-9. [QxMD MEDLINE Link].
Gantner S, Rütten A, Requena L, Gassenmaier G, Landthaler M, Hafner C. CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis. J Cutan Pathol. 2014 Oct. 41 (10):787-90. [QxMD MEDLINE Link].
Barr RJ, Plank CJ. Verruciform xanthoma of the skin. J Cutan Pathol. 1980 Dec. 7(6):422-8. [QxMD MEDLINE Link].
Kurban M, Abbas O, Ghosn S, Kibbi AG. Late evolution of giant verruciform xanthoma in the setting of CHILD syndrome. Pediatr Dermatol. 2010 Sep-Oct. 27(5):551-3. [QxMD MEDLINE Link].
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. 1992 Apr. 98(4):442-9. [QxMD MEDLINE Link].
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. 1992 Sep. 128(9):1213-22. [QxMD MEDLINE Link].
Goldyne ME, Williams ML. CHILD syndrome. Phenotypic dichotomy in eicosanoid metabolism and proliferative rates among cultured dermal fibroblasts. J Clin Invest. 1989 Jul. 84(1):357-60. [QxMD MEDLINE Link].
König A, Skrzypek J, Löffler H, Oeffner F, Grzeschik KH, Happle R. Donor dominance cures CHILD nevus. Dermatology. 2010. 220(4):340-5. [QxMD MEDLINE Link].
Alexopoulos A, Kakourou T. CHILD Syndrome: Successful Treatment of Skin Lesions with Topical Simvastatin/Cholesterol Ointment--A Case Report. Pediatr Dermatol. 2015 Jul-Aug. 32 (4):e145-7. [QxMD MEDLINE Link].
Happle R. Child Syndrome. Orphanet: The portal for rare diseases and orphan drugs. Available at https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=139. May 2013; Accessed: July 30, 2019.

Media Gallery

of 0

Author

Amanda T Moon, MD Clinical Assistant Professor of Dermatology, Children's Hospital of Philadelphia

Amanda T Moon, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Jaclyn Rosenthal Perelman School of Medicine at the University of Pennsylvania

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster 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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Abdul-Ghani Kibbi, MD, FACP Professor and Chair, Department of Dermatology, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

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, Medical Director, Health Cosmetic and Laser Center, University of South Florida College of Medicine

Disclosure: Received none from Abbvie for speaking and teaching; Received none from Valeant for speaking and teaching.

Garrett J Nelson, MD Resident Physician, Department of Dermatology, University of South Florida Morsani College of Medicine

Garrett J Nelson, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Acknowledgements

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.

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.

Babak Roshdieh, MD Consulting Staff, Department of Dermatology, Sierra View District Hospital

Disclosure: Nothing to disclose.

CHILD Syndrome Workup

Laboratory Studies

Imaging Studies

Other Tests

Procedures

Histologic Findings

References

Tables

Contributor Information and Disclosures

What would you like to print?