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Genetics Home Reference: your guide to understanding genetic conditions
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Hand-foot-genital syndrome

Reviewed April 2008

What is hand-foot-genital syndrome?

Hand-foot-genital syndrome is a rare condition that affects the development of the hands and feet, the urinary tract, and the reproductive system. People with this condition have abnormally short thumbs and first (big) toes, small fifth fingers that curve inward (clinodactyly), short feet, and fusion or delayed hardening of bones in the wrists and ankles. The other bones in the arms and legs are normal.

Abnormalities of the genitals and urinary tract can vary among affected individuals. Many people with hand-foot-genital syndrome have defects in the ureters, which are tubes that carry urine from each kidney to the bladder, or in the urethra, which carries urine from the bladder to the outside of the body. Recurrent urinary tract infections and an inability to control the flow of urine (urinary incontinence) have been reported. About half of males with this disorder have the urethra opening on the underside of the penis (hypospadias).

People with hand-foot-genital syndrome are usually able to have children (fertile). In some affected females, problems in the early development of the uterus can later increase the risk of pregnancy loss, premature labor, and stillbirth.

How common is hand-foot-genital syndrome?

Hand-foot-genital syndrome is very rare; only a few families with the condition have been reported worldwide.

What genes are related to hand-foot-genital syndrome?

Mutations in the HOXA13 gene cause hand-foot-genital syndrome. The HOXA13 gene provides instructions for producing a protein that plays an important role in development before birth. Specifically, this protein appears to be critical for the formation and development of the limbs (particularly the hands and feet), urinary tract, and reproductive system. Mutations in the HOXA13 gene cause the characteristic features of hand-foot-genital syndrome by disrupting the early development of these structures. Some mutations in the HOXA13 gene result in the production of a nonfunctional version of the HOXA13 protein. Other mutations alter the protein's structure and interfere with its normal function within cells. Mutations that result in an altered but functional HOXA13 protein may cause more severe signs and symptoms than mutations that lead to a nonfunctional HOXA13 protein.

Related Gene(s)

Changes in this gene are associated with hand-foot-genital syndrome.

  • HOXA13

How do people inherit hand-foot-genital syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of hand-foot-genital syndrome?

These resources address the diagnosis or management of hand-foot-genital syndrome and may include treatment providers.

  • Gene Review: Hand-Foot-Genital Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1423/)
  • Genetic Testing Registry: Hand foot uterus syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1841679)
  • MedlinePlus Encyclopedia: Hypospadias (http://www.nlm.nih.gov/medlineplus/ency/article/001286.htm)
  • MedlinePlus Encyclopedia: Urinary Tract Infection (http://www.nlm.nih.gov/medlineplus/ency/article/000521.htm)

You might also find information on the diagnosis or management of hand-foot-genital syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/hand-foot-genital-syndrome/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 hand-foot-genital syndrome?

You may find the following resources about hand-foot-genital syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Hypospadias (http://www.nlm.nih.gov/medlineplus/ency/article/001286.htm)
    • Encyclopedia: Urinary Tract Infection (http://www.nlm.nih.gov/medlineplus/ency/article/000521.htm)
    • Health Topic: Foot Injuries and Disorders (http://www.nlm.nih.gov/medlineplus/footinjuriesanddisorders.html)
    • Health Topic: Hand Injuries and Disorders (http://www.nlm.nih.gov/medlineplus/handinjuriesanddisorders.html)

  • Educational resources - Information pages

    • American Society for Surgery of the Hand: Congenital Hand Differences (http://www.assh.org/Public/HandConditions/Pages/CongenitalHandDifferences.aspx)
    • Cleveland Clinic: Congenital Hand Differences (http://my.clevelandclinic.org/orthopaedics-rheumatology/diseases-conditions/congenital-hand.aspx)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2438)

  • Patient support - For patients and families

    • Family Village: Limb Differences (http://www.familyvillage.wisc.edu/lib_ampu.htm)
    • March of Dimes: Genital and Urinary Tract Defects (http://www.marchofdimes.com/baby/birthdefects_genital.html)
    • 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/NBK1423/)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Hand foot uterus syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1841679)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((hand-foot-genital%20syndrome)%20OR%20(hand-foot-uterus%20syndrome))%20AND%20english%5Bla%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/140000)

What other names do people use for hand-foot-genital syndrome?

  • Hand-foot-uterus syndrome
  • HFGS
  • HFG syndrome
  • HFU syndrome

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 hand-foot-genital syndrome?

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

What glossary definitions help with understanding hand-foot-genital syndrome?

autosomal ; autosomal dominant ; cell ; clinodactyly ; duct ; gene ; genitals ; homeobox ; homeodomain ; hypospadias ; incontinence ; kidney ; mutation ; protein ; syndrome ; urinary incontinence

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

References

  • Gene Review: Hand-Foot-Genital Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1423/)
  • Goodman FR, Bacchelli C, Brady AF, Brueton LA, Fryns JP, Mortlock DP, Innis JW, Holmes LB, Donnenfeld AE, Feingold M, Beemer FA, Hennekam RC, Scambler PJ. Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Genet. 2000 Jul;67(1):197-202. Epub 2000 Jun 5. (http://www.ncbi.nlm.nih.gov/pubmed/10839976?dopt=Abstract)
  • Goodman FR, Scambler PJ. Human HOX gene mutations. Clin Genet. 2001 Jan;59(1):1-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11206481?dopt=Abstract)
  • Goodman FR. Limb malformations and the human HOX genes. Am J Med Genet. 2002 Oct 15;112(3):256-65. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12357469?dopt=Abstract)
  • Innis JW, Mortlock D, Chen Z, Ludwig M, Williams ME, Williams TM, Doyle CD, Shao Z, Glynn M, Mikulic D, Lehmann K, Mundlos S, Utsch B. Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model. Hum Mol Genet. 2004 Nov 15;13(22):2841-51. Epub 2004 Sep 22. (http://www.ncbi.nlm.nih.gov/pubmed/15385446?dopt=Abstract)
  • Mortlock DP, Innis JW. Mutation of HOXA13 in hand-foot-genital syndrome. Nat Genet. 1997 Feb;15(2):179-80. (http://www.ncbi.nlm.nih.gov/pubmed/9020844?dopt=Abstract)
  • Utsch B, McCabe CD, Galbraith K, Gonzalez R, Born M, Dötsch J, Ludwig M, Reutter H, Innis JW. Molecular characterization of HOXA13 polyalanine expansion proteins in hand-foot-genital syndrome. Am J Med Genet A. 2007 Dec 15;143A(24):3161-8. (http://www.ncbi.nlm.nih.gov/pubmed/17935235?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: April 2008
Published: May 20, 2013