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Pallister-Hall Syndrome (PHS)

Last updated Dec. 15, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Pallister-Hall Syndrome (PHS) is an infrequent, autosomal dominant, genetic developmental disorder that affects multiple parts of the body.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Cerebroacrovisceral Early Lethality (CAVE) Complex
  • Hypothalamic Hamartoblastoma Syndrome
  • Isochromosome 12p Syndrome

What is Pallister-Hall Syndrome? (Definition/Background Information)

  • Pallister-Hall Syndrome (PHS) is an infrequent, autosomal dominant, genetic developmental disorder that affects multiple parts of the body
  • The growth of a tumor at the hypothalamus region of the brain (called hypothalamic hamartoma) is a distinct feature of this syndrome. It may cause serious medical complications in a few individuals
  • Individuals with PHS have additional digits on the hands and feet. The webbing between some fingers or toes may also be joined together
  • Treatment of the condition is based on the severity and type of symptoms presented
  • Prognosis is dependent on many factors, including the signs and symptoms and access to early treatment. The prognosis is generally guarded

Who gets Pallister-Hall Syndrome? (Age and Sex Distribution)

  • Pallister-Hall Syndrome is an extremely rare condition that manifests itself at birth
  • No particular gender, racial, or ethnic preference has been noted

What are the Risk Factors for Pallister-Hall Syndrome? (Predisposing Factors)

Potential risk factor for Pallister-Hall Syndrome is:

  • The condition is transmitted genetically from the parents to their offspring. Hence, those with a positive family history of PHS, have a high risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pallister-Hall Syndrome? (Etiology)

  • Pallister-Hall Syndrome is inherited as an autosomal dominant condition
  • An error in gene (GLI3 gene) mutation, leading to the defective production of a protein by the body causes PHS. This protein is responsible for regulating the shape and form of certain organs and tissues, during the fetal development stage
  • The exact mechanism of how the defective gene causes adverse multiple developmental abnormalities, is yet to be fully understood
  • These defective genes may be inherited from any one of the parent to cause PHS, since the disorder is autosomal dominant. However, these genes are sometimes, also known to mutate spontaneously in the prenatal stage; even though there is no family history of the condition

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children who do not inherit the abnormal gene will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Pallister-Hall Syndrome?

The signs and symptoms of Pallister-Hall Syndrome depend on the severity of the condition. Individuals with a mild variety have fewer signs and symptoms, as compared to those with the severe type. These include:

  • Abnormal tumor-like growth in the hypothalamus (located within the brain). This may cause sudden epileptic ‘hollow-laughter’ type seizures, starting from a young age (3-4 years)
  • Extra fingers and toes, fused skin between fingers or toes may be seen. Additional fingers and toes is called polydactyly; fusing of the skin between the fingers and toes is called syndactyly
  • Bifid epiglottis - a condition where the airways are improperly formed. This may cause speech difficulties
  • Laryngeal cleft - existence of a gap between the food pipe and windpipe (bronchus), causing food or fluid to pass into the windpipe. Such aspiration of food frequently into the lungs, results in aspiration pneumonia
  • Anal atresia - anal opening may remain obstructed, for which an emergency surgical procedure to remove the obstruction will have to be performed at birth
  • Kidney function may be affected resulting in signs and symptoms, due to kidney failure

How is Pallister-Hall Syndrome Diagnosed?

Diagnosis steps include a primary physical examination of the individual and gathering information related to family history of Pallister-Hall Syndrome. The characteristic body features and clinical findings may help a physician suspect the disorder.

Some of the diagnostic tests performed include:

  • Molecular genetic analysis
  • Prenatal diagnosis (during pregnancy)
  • MRI scan of brain, to determine the presence of brain tumors
  • X-rays, to screen for bone defects

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pallister-Hall Syndrome?

Complications due to mild Pallister-Hall Syndrome are generally uncommon. But, if PHS is severe, then the condition could be serious and the complications might include:

  • The unborn infant may suffer from pituitary insufficiency, leading to reduced adrenalin production, which could be fatal for the fetus. Diagnosis and treatment of this condition is very difficult in an unborn developing baby
  • Treatment of hypothalamus insufficiency (poorly functioning hypothalamus) may result in many complications necessitating lifelong support and medications
  • The individual may suffer from ADD (attention deficit disorder)
  • Frequent convulsions may result in injury to the tongue, or to the body due to a fall, during convulsion episodes
  • Precocious puberty (onset of puberty before age 7-8 years in children) may occur due to hormonal imbalance in the sex hormones

How is Pallister-Hall Syndrome Treated?

Treatment and management of Pallister-Hall Syndrome is based on the severity of the condition and signs and symptoms presented. The treatment measures include:

  • Surgical procedures to treat the hypothalamus tumor are recommended, if the tumor causes significant signs and symptoms and related medical complications. If the hypothalamus tumor is small and does not cause significant signs and symptoms, the healthcare provider may then choose to avoid any surgical procedures to remove the tumor. Surgical removal of the hypothalamus tumor is generally made on a case-by-case basis
  • Correctional surgery is performed to rectify hand and feet abnormalities (such as additional fingers or toes, fused skin between the fingers and toes)
  • If endocrine abnormalities are observed, then these require urgent treatment. It is especially important to address hormonal deficiencies and correct any imbalances
  • The airways and epiglottis are treated based on the extent of the food pipe or windpipe defects
  • Surgery is performed if anal atresia (anal blockage) is present
  • Epileptic seizures are managed symptomatically with suitable medications
  • If there are developmental delays, then supportive care and therapies are administered
  • Young children should undergo regular (annual) medical examination/screening, in order for the healthcare provider to assess their growth, and to also check for any indications of precocious puberty

How can Pallister-Hall Syndrome be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Pallister-Hall Syndrome genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Pallister-Hall Syndrome? (Outcomes/Resolutions)

  • Pallister-Hall Syndrome is a very rare developmental disorder, which may be fatal during the fetal development stage. In such cases, death may occur from hormonal abnormalities or pituitary insufficiency
  • The prognoses depend on the severity of the signs and symptoms. Individuals with milder PHS have much better prognosis than individuals with severe conditions
  • Both mild and severe forms of the condition are treated symptomatically. In some cases, lifelong medications and supportive care is necessary

Additional and Relevant Useful Information for Pallister-Hall Syndrome:

Pallister-Hall Syndrome is also known as Cerebroacrovisceral Early Lethality Complex (or CAVE Complex).

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Dec. 29, 2013
Last updated: Dec. 15, 2018