Sections

CHILD Syndrome

Presentation

History

CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome is a congenital disorder, often with a constellation of striking physical anomalies that assist the clinician in making the diagnosis.^[19]Nevertheless, taking a careful history and review of systems, in addition to performing a physical examination and further testing, is important in order to determine the extent of involvement in the individual patient. In addition, the family history should also be explored. Although the majority of CHILD syndrome cases are sporadic, there is a known X-linked dominant inheritance pattern. Reports have described families in which there is extreme X-inactivation resulting in milder and limited clinical features of the disease. Therefore, a thorough history may reveal an X-linked dominant pattern.^[20]

Physical Examination

CHILD syndrome is a disorder with ipsilateral involvement of the skin, the viscera, and the musculoskeletal and central nervous systems.

Skin and nails

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.^[21]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 contralateral side, and bilateral, symmetric involvement has been described.^{[6, 22]}Skin lesions seen in CHILD syndrome typically involve the neck, body, extremities, and perineum.^[8]Unilateral ptychotropism, or affinity for body folds, is common.^[23]The most frequently affected skinfolds are the vulva, axillae, and gluteal folds.

Verruciform xanthomas (VXs) have also been associated with CHILD syndrome; VXs are rare benign tumors usually found on the oral mucosa or in the anogenital region, but the VXs found in CHILD syndrome are usually nonoral and nongenital.^[24]VXs are also associated with chronic inflammation, graft versus host disease, and lymphedema.^[25]

The nails are also commonly affected in CHILD syndrome. According to the Human Phenotype Ontology database, 30-79% of people have nail abnormalities and hyperkeratosis.^[11]Additionally, a scarring alopecia can occur, most often on the affected side.^{[16, 26]}

Musculoskeletal

Musculoskeletal abnormalities include ipsilateral limb reduction defects ranging from hypoplasia of the phalanges to 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.^[27]Unilateral epiphyseal stippling of the pelvis, ribs, vertebrae, and extremities can be noted on radiographs in infants.^[3]Of individuals with CHILD syndrome, 80-99% have aplasia/hypoplasia of the extremities and epiphyseal stippling.^[11]

Viscera

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, lungs, thyroid, and reproductive tract. The ipsilateral kidney also may be involved. Cardiovascular malformations are the most common causes of early death and are encountered most often in left-sided cases.

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.

Differential Diagnoses

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 Clinical Presentation

History

Physical Examination

Skin and nails

Musculoskeletal

Viscera

Complications

References

Tables

Contributor Information and Disclosures

What would you like to print?