National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Pallister-Hall syndrome

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Other Names:
PHS; Hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly; Pallister Hall syndrome
Categories:
Pallister-Hall syndrome (PHS) is a genetic disease that affects the development of many parts of the body. Common features include extra fingers and/or toes (polydactyly), extra skin between the fingers or toes (syndactyly), an abnormal growth in the brain called a hypothalamic hamartoma, and a malformation of the airway known as bifid epiglottis.[1] The bifid epiglottis in rare cases may lead to respiratory failure. While the hypothalamic hamartoma in most cases does not cause problems, in some cases it may cause neurological problems such as seizures, growth hormone deficiency, precocious puberty, or a deficiency of many hormones (panhypopituitarism) that can result in cortisol deficiency. Other symptoms of PHS may include imperforate anus, abnormalities in the kidneys, heart defects, small genitalia, lack of fingers, nail problems, cleft palate, bifid uvula, and development delay and behavioral problems.[1][2][3][4][5][6] 

Pallister-Hall syndrome is caused by mutations in the GLI3 gene. Inheritance is autosomal dominant, however, in about a quarter of cases Pallister-Hall syndrome results from a new (de novo) mutation.[1][5]

The diagnosis of Pallister-Hall syndrome can be made when there is a hypothalamic hamartoma and polydactyly. The genetic test that identifies a mutation in the GLI3 gene confirms the diagnosis. Treatment is based on the symptoms, and may include medication for the early treatment of cortisol deficiency and seizures, surgery for imperforate anus and/or polydactyly, and special education when developmental delays are present.[6] The prognosis depends on which symptoms are present and their severity.[1]
Last updated: 11/20/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Hypothalamic hamartoma 0002444
30%-79% of people have these symptoms
3-4 finger cutaneous syndactyly 0011939
Abnormal basal ganglia MRI signal intensity 0012751
Abnormal prolactin level 0040086
Accessory oral frenulum 0000191
Adrenocorticotropic hormone deficiency 0011748
Anal atresia
Absent anus
0002023
Anteverted nares
Upturned nasal tip
Nasal tip, upturned
Upturned nose
Upturned nostrils
[ more ] 		0000463
Atresia of the external auditory canal
Absent ear canal
0000413
Bifid uvula 0000193
Bilateral postaxial polydactyly 0006136
Brachydactyly
Short fingers or toes
0001156
Broad thumb
Broad thumbs
Wide/broad thumb
[ more ] 		0011304
Central adrenal insufficiency 0011734
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Gonadotropin deficiency 0008213
Hemivertebrae
Missing part of vertebrae
0002937
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ] 		0002827
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Laryngeal cleft 0008751
Low-set, posteriorly rotated ears 0000368
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Microphthalmia
Abnormally small eyeball
0000568
Microtia
Underdeveloped ears
Small ears
[ more ] 		0008551
Nail dysplasia
Atypical nail growth
0002164
Natal tooth
Born with teeth
Teeth present at birth
[ more ] 		0000695
Pituitary hypothyroidism
Low thyroid gland function due to abnormal pituitary gland
0008245
Polydactyly affecting the 3rd finger
Extra middle finger
0009958
Polydactyly affecting the 4th finger
Extra ring finger
0009971
Ptosis
Drooping upper eyelid
0000508
Radial bowing
Bowing of outer large bone of the forearm
0002986
Radial head subluxation 0003048
Recurrent upper and lower respiratory tract infections 0200117
Renal dysplasia 0000110
Rib fusion
Fused ribs
0000902
Secondary growth hormone deficiency 0008240
Short 4th metacarpal
Shortened 4th long bone of hand
0010044
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Skeletal dysplasia 0002652
Supernumerary metacarpal bones
Extra long bones of hand
0005917
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
5%-29% of people have these symptoms
Abnormal corpus callosum morphology 0001273
Abnormal lung lobation 0002101
Adrenal hypoplasia
Small adrenal glands
0000835
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Atrioventricular canal defect 0006695
Auricular tag 0030021
Bifid epiglottis 0010564
Broad toe
Wide toe
0001837
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum
[ more ] 		0001321
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity
[ more ] 		0000453
Cleft lip 0410030
Cleft upper lip
Harelip
0000204
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta
[ more ] 		0001680
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Decreased testicular size
Small testes
Small testis
[ more ] 		0008734
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Ectopic kidney
Abnormal kidney location
Displaced kidney
[ more ] 		0000086
Facial grimacing 0000273
Focal emotional seizure with laughing 0010821
Global developmental delay 0001263
Holoprosencephaly 0001360
Hypospadias 0000047
Inguinal hernia 0000023
Large for gestational age
Birth weight > 90th percentile
Birthweight > 90th percentile
[ more ] 		0001520
Microglossia
Underdevelopment of the tongue
Abnormally small tongue
[ more ] 		0000171
Micropenis
Short penis
Small penis
[ more ] 		0000054
Microretrognathia
Small retruded chin
0000308
Midline facial capillary hemangioma 0007601
Oligodactyly 0012165
Overlapping toe
Overlapping toes
Overriding toes
[ more ] 		0001845
Panhypopituitarism 0000871
Paroxysmal bursts of laughter 0000749
Patent ductus arteriosus 0001643
Precocious puberty
Early onset of puberty
Early puberty
[ more ] 		0000826
Primary adrenal insufficiency 0008207
Thyroid hypoplasia 0005990
Umbilical hernia 0001537
Unilateral renal agenesis
Absent kidney on one side
Missing one kidney
Single kidney
[ more ] 		0000122
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
1%-4% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia
[ more ] 		0000062
Aplasia/hypoplasia of the uterus
Absent/small uterus
Absent/underdeveloped uterus
[ more ] 		0008684
Aplasia/Hypoplasia of the vagina
Absent/small vagina
Absent/underdeveloped vagina
[ more ] 		0011026
Arrhinencephaly 0002139
Bilateral renal agenesis 0010958
Distal arthrogryposis 0005684
Hydrometrocolpos 0030010
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Mesomelia
Disproportionately short middle portion of limb
0003027
Oligohydramnios
Low levels of amniotic fluid
0001562
Osteochondroma 0030431
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Respiratory insufficiency
Respiratory impairment
0002093
Scaphocephaly 0030799
Scrotal hypoplasia
Smaller than typical growth of scrotum
0000046
Talipes 0001883
Trigonocephaly
Triangular skull shape
Wedge shaped skull
[ more ] 		0000243
Y-shaped metacarpals
Y-shaped long bone of hand
0006042
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Decreased circulating cortisol level
Low blood cortisol level
0008163
Distal shortening of limbs
Short outer part of limbs
0006402
Distal urethral duplication 0008706
Growth hormone deficiency 0000824
Hydronephrosis 0000126
Hydroureter 0000072
Hypoplasia of the epiglottis 0005349
Mesoaxial foot polydactyly
Central polydactyly of feet
0010112
Mesoaxial hand polydactyly 0006159
Neonatal death
Neonatal lethal
0003811
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger
[ more ] 		0001162
Preductal coarctation of the aorta 0005151
Renal cyst
Kidney cyst
0000107
Renal hypoplasia
Small kidneys
Underdeveloped kidneys
[ more ] 		0000089
Seizure 0001250
Thyroid dysgenesis 0008188
Variable expressivity 0003828
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include oral-facial-digital syndrome type 6, Holzgreve-Wagner-Rehder syndrome, McKusick-Kaufman syndrome, Holt-Oram syndrome, Bardet-Biedl syndrome, Smith-Lemli-Opitz syndrome, as well as craniopharyngioma, Greig cephalopolysyndactyly syndrome Ellis Van Creveld syndrome (see these terms) and congenital hypothalamic hamartoma syndrome.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Pallister-Hall syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Pallister-Hall syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Pallister-Hall syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Biesecker LG. Pallister-Hall Syndrome. Gene Review. 2017; http://www.ncbi.nlm.nih.gov/books/NBK1465/.
  2. Fundación Cavanna. Sindrome de Pallister-Hall. Educacion especial Espanola. http://www.webespecial.com/sindromes/h6.htm.
  3. Azzam A & cols. Psychiatric and neuropsychological characterization of Pallister-Hall syndrome. Clin Genet. 2005; 67(1):87-92.
  4. Johnston JJ & cols. 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; 76:609-22. http://www.ncbi.nlm.nih.gov/pubmed/15739154.
  5. Pallister-Hall syndrome. Genetics Home Reference. November, 2016; http://ghr.nlm.nih.gov/condition/pallister-hall-syndrome.
  6. Biesecker L. Pallister-Hall syndrome. Orphanet. May 2013; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=672.