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Genetics Home Reference: your guide to understanding genetic conditions
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Congenital hemidysplasia with ichthyosiform erythroderma and limb defects

(often shortened to CHILD syndrome)
Reviewed July 2008

What is CHILD syndrome?

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects, more commonly known by the acronym CHILD syndrome, is a condition that affects the development of several parts of the body. The signs and symptoms of this disorder are typically limited to either the right side or the left side of the body. ("Hemi-" means "half," and "dysplasia" refers to abnormal growth.) The right side is affected about twice as often as the left side.

People with CHILD syndrome have a skin condition characterized by large patches of skin that are red and inflamed (erythroderma) and covered with flaky scales (ichthyosis). This condition is most likely to occur in skin folds and creases and usually does not affect the face. The skin abnormalities are present at birth and persist throughout life.

CHILD syndrome also disrupts the formation of the arms and legs during early development. Children with this disorder may be born with one or more limbs that are shortened or missing. The limb abnormalities occur on the same side of the body as the skin abnormalities.

Additionally, CHILD syndrome may affect the development of the brain, heart, lungs, and kidneys.

How common is CHILD syndrome?

CHILD syndrome is a rare disorder; it has been reported in about 60 people worldwide. This condition occurs almost exclusively in females.

What genes are related to CHILD syndrome?

Mutations in the NSDHL gene cause CHILD syndrome. This gene provides instructions for making an enzyme that is involved in the production of cholesterol. Cholesterol is a type of fat that is produced in the body and obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally both before and after birth. Cholesterol is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.

The mutations that underlie CHILD syndrome eliminate the activity of the NSDHL enzyme, which disrupts the normal production of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol production to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupt the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol production leads to the specific features of CHILD syndrome.

Related Gene(s)

Changes in this gene are associated with congenital hemidysplasia with ichthyosiform erythroderma and limb defects.

  • NSDHL

How do people inherit CHILD syndrome?

This condition has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.

Most cases of CHILD syndrome occur sporadically, which means only one member of a family is affected. Rarely, the condition can run in families and is passed from mother to daughter. Researchers believe that CHILD syndrome occurs almost exclusively in females because affected males die before birth. Only one male with CHILD syndrome has been reported.

Where can I find information about diagnosis or management of CHILD syndrome?

These resources address the diagnosis or management of CHILD syndrome and may include treatment providers.

  • Gene Review: NSDHL-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK51754/)
  • Genetic Testing Registry: Child syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265267)

You might also find information on the diagnosis or management of CHILD syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/congenital-hemidysplasia-with-ichthyosiform-erythroderma-and-limb-defects/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about CHILD syndrome?

You may find the following resources about CHILD syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    Health Topic: Skin Conditions (http://www.nlm.nih.gov/medlineplus/skinconditions.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6039/resources/resources/1)

  • Educational resources - Information pages

    • Children's Hospital Boston: Congenital Limb Defects (http://www.childrenshospital.org/az/Site1157/mainpageS1157P0.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=139)

  • Patient support - For patients and families

    • Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T.) (http://www.firstskinfoundation.org/)
    • National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/549/viewAbstract)
    • Resource list from the University of Kansas Medical Center: Limb Anomalies (http://www.kumc.edu/gec/support/limb.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK51754/)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Child syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265267)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22congenital%20hemidysplasia%20with%20ichthyosiform%20erythroderma%20and%20limb%20defects%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((congenital%20hemidysplasia%20AND%20ichthyosiform%20erythroderma%5BTIAB%5D)%20OR%20(child%20syndrome%20AND%20NSDHL%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/308050)

What other names do people use for CHILD syndrome?

  • Ichthyosiform erythroderma, unilateral, with ipsilateral malformations, especially absence deformity of limbs

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about CHILD syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding CHILD syndrome?

acids ; cell ; cholesterol ; chromosome ; congenital ; digestive ; dysplasia ; egg ; enzyme ; erythroderma ; gene ; ichthyosiform ; ichthyosis ; inheritance ; pattern of inheritance ; sex chromosomes ; syndrome ; toxic ; unilateral ; X-linked dominant

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bittar M, Happle R, Grzeschik KH, Leveleki L, Hertl M, Bornholdt D, König A. CHILD syndrome in 3 generations: the importance of mild or minimal skin lesions. Arch Dermatol. 2006 Mar;142(3):348-51. (http://www.ncbi.nlm.nih.gov/pubmed/16549711?dopt=Abstract)
  • Herman GE. Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R75-88. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12668600?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12966526?dopt=Abstract)
  • Kaminska-Winciorek G, Brzezinska-Wcisło 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. (http://www.ncbi.nlm.nih.gov/pubmed/17448011?dopt=Abstract)
  • Kim CA, Konig A, Bertola DR, Albano LM, Gattás GJ, Bornholdt D, Leveleki L, Happle R, Grzeschik KH. CHILD syndrome caused by a deletion of exons 6-8 of the NSDHL gene. Dermatology. 2005;211(2):155-8. (http://www.ncbi.nlm.nih.gov/pubmed/16088165?dopt=Abstract)
  • König 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10710235?dopt=Abstract)
  • König A, Happle R, Fink-Puches R, Soyer HP, Bornholdt D, Engel H, Grzeschik KH. 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. (http://www.ncbi.nlm.nih.gov/pubmed/11907515?dopt=Abstract)
  • Porter FD. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr. 2003 Dec;15(6):607-13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14631207?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2008
Published: May 20, 2013