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Pallister-Hall syndrome

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Description

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 health 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.

Frequency

This condition is very rare; its prevalence is unknown.

Causes

Mutations in the GLI3 gene cause Pallister-Hall syndrome. This 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 is uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.

Inheritance

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.

Other Names for This Condition

  • Hall-Pallister syndrome
  • PHS

Additional Information & Resources

Genetic and Rare Diseases Information Center

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • 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. Citation on PubMed
  • Biesecker LG. Pallister-Hall Syndrome. 2000 May 25 [updated 2017 May 18]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews┬« [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1465/ Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • Johnston JJ, Sapp JC, Turner JT, Amor D, Aftimos S, Aleck KA, Bocian M, Bodurtha JN, Cox GF, Curry CJ, Day R, Donnai D, Field M, Fujiwara I, Gabbett M, Gal M, Graham JM, Hedera P, Hennekam RC, Hersh JH, Hopkin RJ, Kayserili H, Kidd AM, Kimonis V, Lin AE, Lynch SA, Maisenbacher M, Mansour S, McGaughran J, Mehta L, Murphy H, Raygada M, Robin NH, Rope AF, Rosenbaum KN, Schaefer GB, Shealy A, Smith W, Soller M, Sommer A, Stalker HJ, Steiner B, Stephan MJ, Tilstra D, Tomkins S, Trapane P, Tsai AC, Van Allen MI, Vasudevan PC, Zabel B, Zunich J, Black GC, Biesecker LG. Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. Hum Mutat. 2010 Oct;31(10):1142-54. doi: 10.1002/humu.21328. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • 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. Citation on PubMed
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