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Genetics Home Reference: your guide to understanding genetic conditions
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Pallister-Hall syndrome

Reviewed March 2006

What is Pallister-Hall syndrome?

Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.

How common is Pallister-Hall syndrome?

This condition is very rare; its prevalence is unknown.

What genes are related to Pallister-Hall syndrome?

Mutations in the GLI3 gene cause Pallister-Hall syndrome.

The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.

Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It remains uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.

Related Gene(s)

Changes in this gene are associated with Pallister-Hall syndrome.

  • GLI3

How do people inherit Pallister-Hall 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 a mutation in the GLI3 gene 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 Pallister-Hall syndrome?

These resources address the diagnosis or management of Pallister-Hall syndrome and may include treatment providers.

  • Gene Review: Pallister-Hall Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1465/)
  • Genetic Testing Registry: Pallister-Hall syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265220)
  • MedlinePlus Encyclopedia: Epiglottis (Image) (http://www.nlm.nih.gov/medlineplus/ency/imagepages/19595.htm)
  • MedlinePlus Encyclopedia: Imperforate Anus (http://www.nlm.nih.gov/medlineplus/ency/article/001147.htm)
  • MedlinePlus Encyclopedia: Polydactyly (http://www.nlm.nih.gov/medlineplus/ency/article/003176.htm)

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

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

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

What other names do people use for Pallister-Hall syndrome?

  • CAVE complex
  • cerebroacrovisceral early lethality complex
  • Hall-Pallister syndrome
  • hypothalamic hamartoblastoma syndrome
  • PHS

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 Pallister-Hall syndrome?

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

What glossary definitions help with understanding Pallister-Hall syndrome?

anus ; autosomal ; autosomal dominant ; bifid ; cell ; cutaneous ; epiglottis ; gene ; gene expression ; hamartoma ; hormone ; imperforate anus ; inherited ; kidney ; malformation ; mutation ; obstruction ; polydactyly ; prevalence ; protein ; syndactyly ; syndrome

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

References

  • Azzam A, Lerner DM, Peters KF, Wiggs E, Rosenstein DL, Biesecker LG. Psychiatric and neuropsychological characterization of Pallister-Hall syndrome. Clin Genet. 2005 Jan;67(1):87-92. (http://www.ncbi.nlm.nih.gov/pubmed/15617553?dopt=Abstract)
  • Biesecker LG, Abbott M, Allen J, Clericuzio C, Feuillan P, Graham JM Jr, Hall J, Kang S, Olney AH, Lefton D, Neri G, Peters K, Verloes A. Report from the workshop on Pallister-Hall syndrome and related phenotypes. Am J Med Genet. 1996 Oct 2;65(1):76-81. (http://www.ncbi.nlm.nih.gov/pubmed/8914745?dopt=Abstract)
  • Boudreau EA, Liow K, Frattali CM, Wiggs E, Turner JT, Feuillan P, Sato S, Patsalides A, Patronas N, Biesecker LG, Theodore WH. Hypothalamic hamartomas and seizures: distinct natural history of isolated and Pallister-Hall syndrome cases. Epilepsia. 2005 Jan;46(1):42-7. (http://www.ncbi.nlm.nih.gov/pubmed/15660767?dopt=Abstract)
  • Gene Review: Pallister-Hall Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1465/)
  • Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet. 2005 Apr;76(4):609-22. Epub 2005 Feb 28. (http://www.ncbi.nlm.nih.gov/pubmed/15739154?dopt=Abstract)
  • Kang S, Graham JM Jr, Olney AH, Biesecker LG. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat Genet. 1997 Mar;15(3):266-8. (http://www.ncbi.nlm.nih.gov/pubmed/9054938?dopt=Abstract)
  • McCann E, Fryer AE, Craigie R, Baillie C, Ba'ath ME, Selby A, Biesecker LG. Genitourinary malformations as a feature of the Pallister-Hall syndrome. Clin Dysmorphol. 2006 Apr;15(2):75-9. (http://www.ncbi.nlm.nih.gov/pubmed/16531732?dopt=Abstract)
  • Ng D, Johnston JJ, Turner JT, Boudreau EA, Wiggs EA, Theodore WH, Biesecker LG. Gonadal mosaicism in severe Pallister-Hall syndrome. Am J Med Genet A. 2004 Jan 30;124A(3):296-302. Erratum in: Am J Med Genet A. 2005 Jul 15;136(2):225. (http://www.ncbi.nlm.nih.gov/pubmed/14708104?dopt=Abstract)
  • Ondrey F, Griffith A, Van Waes C, Rudy S, Peters K, McCullagh L, Biesecker LG. Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome. Am J Med Genet. 2000 Sep 4;94(1):64-7. (http://www.ncbi.nlm.nih.gov/pubmed/10982485?dopt=Abstract)
  • Roscioli T, Kennedy D, Cui J, Fonseca B, Watson GF, Pereira J, Xie YG, Mowat D. Pallister-Hall syndrome: unreported skeletal features of a GLI3 mutation. Am J Med Genet A. 2005 Aug 1;136A(4):390-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16007608?dopt=Abstract)
  • Stevens CA, Ledbetter JC. Significance of bifid epiglottis. Am J Med Genet A. 2005 May 1;134(4):447-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15782417?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: March 2006
Published: August 18, 2014