FaCD Online Syndrome Fact Sheet

Last updated: 12 May 2009

Name: Pallister-Hall syndrome

Mode of Inheritance: AD

OMIM number: 146510  


GLI3, mapped to 7p13

Tumor features

hypothalamic hamartoma / hamartoblastoma

Non-tumor features

ears, malformed
epiglottis, bifid
imperforate anus
nails, small, dysplastic
syndactyly of fingers
syndactyly of toes


Hallmarks of this syndrome are hypothalamic hamartoma, panhypopituitarism, bifid epiglottis, polydactyly, dysplastic nails and imperforate anus[1]. The hamartomas are usually benign, but may be associated with severe headaches[1].
There is clinical overlap with a number of disorders, including McKusick-Kaufmann, Smith-Lemli-Opitz type II, orofaciodigital syndrome type VI and Congenital Hypothalamic Hamartoma syndrome. Depending on the type of mutations in the GLI3 zinc finger transcription gene, Pallister-Hall syndrome or Greig cephalopolysyndactyly syndrome develops[2].

A. For an index case: both of the following must be present in at least 1 person in a family (index case):

  • 1) hypothalamic hamartoma, confirmed by histology or presenting on MRI (as non-enhancing midline hypothalamic mass that is isodense to gray matter on all pulse sequences)
  • 2) central polydactyly (most commonly including skeletal polydactyly of 3d or 4th digit)

B. For first degree relatives of an index case: both of the following must be present in those relatives:
  • 1) either finding A1 or A2 features (however, postaxial polydactyly may be substituted for central polydactyly).
  • 2) inheritance of A1 or A2 in an autosomal dominant pattern or in a manner consistent with gonadal mosaicism.


Pallister-Hall information on Genetics Home Reference 24 1 08


[1] Biesecker LG, Graham JM. Pallister-Hall syndrome. J Med Genet 33[7], 585-589. 1996.
[2] 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. American journal of human genetics 2005; 76(4):609-22.
[3] Biesecker LG, Abbott M, Allen J, Clericuzio C, Feuillan P, Graham JM, Hall T, 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 65[1], 76-81. 1996.