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Disease Profile

Pallister-Hall syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PHS; Hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly; Pallister Hall syndrome

Categories

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;

Summary

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]

Symptoms

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.

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
Teeth present at birth
Born with teeth

[ 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

Learn more

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.

References

  1. Biesecker LG. Pallister-Hall Syndrome. Gene Review. 2017; https://www.ncbi.nlm.nih.gov/books/NBK1465/.
  2. Fundación Cavanna. Sindrome de Pallister-Hall. Educacion especial Espanola. https://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. https://www.ncbi.nlm.nih.gov/pubmed/15739154.
  5. Pallister-Hall syndrome. Genetics Home Reference. November, 2016; https://ghr.nlm.nih.gov/condition/pallister-hall-syndrome.
  6. Biesecker L. Pallister-Hall syndrome. Orphanet. May 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=672.

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