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Pallister-Hall Syndrome
Sunday, 18 January 2004
Sunday, 18 January 2004
CAVE complex, congenital hypothalamic hamartoblastoma syndrome


Pallister-Hall syndrome is a very rare genetic disorder characterized by multiple congenital anomalies, which means there are many defects present at birth. Pallister-Hall syndrome is best known by the presence of abnormal fingers and toes, malformations in various parts of the breathing system and a tumor in the hypothalamus (a part of the brain). There is a very wide range of severity of signs and symptoms in children affected with Pallister-Hall syndrome. Some children may be only mildly affected while others may have many symptoms, physical anomalies and malformations. In the most severe form of this syndrome, most babies do not survive beyond the first month of life.


: Pallister-Hall syndrome occurs in all ethnic groups, and males seem to be more affected than females. There are only 100 known cases worldwide, however the variability and severity of symptoms and physical findings can often lead to individuals being misdiagnosed. Until a more definitive database is established, this disorder is still considered to be very rare.

Signs and Symptoms

There are multiple signs and symptoms associated with Pallister-Hall syndrome which can range from very mild to life threateningly severe. The presence of a non-cancerous growth of the hypothalamus (hypothalamic hamartoma) is the most significant abnormality, which affects brain functioning and the hormonal system. Extra fingers and toes which can be webbed are very common. Some of the more severe symptoms noted in the newborn period are abnormally formed lungs, a split in the epiglottis (flap of skin covering the windpipe), a cleft in the larynx (windpipe), abnormal electrolyte levels, low blood sugars, and abnormal or absent kidneys. Children with Pallister-Hall may have none, some or all of these other following symptoms: • Polydactyly (extra fingers or toes) including an extra finger bone between the 3rd and 4th fingers resulting in a “Y” shape • Syndactyly (fused or webbed fingers and/or toes) • Skull or facial abnormalities (flat nasal bridge, short upturned nose, rotated ears, small tongue, dental abnormalities) • Decreased pituitary function (associated with short stature, abnormal testes, electrolyte imbalance, early onset of puberty) • Hydrocephalus (increased fluid in the skull) • Gelastic seizures (involuntary brief outburst of laughter, cough, crying) • Imperforate anus (thin membrane of tissue over rectum) or anal stenosis (absence of anal canal), both causing blockage of stool • Hearing and vision loss

Possible Causes

Pallister-Hall syndrome is a genetic disorder that is caused by an alteration in a gene named GLI3 which is on the short arm of chromosome 7. Since only one abnormal copy of the gene is needed to cause the disease, it is inherited in an autosomal dominant fashion. This means that an affected parent has a 50% chance of passing on the altered gene to a child who will also have the disorder. However, most children with Pallister-Hall syndrome did not inherit the altered gene from one parent. In fact, most cases of Pallister-Hall syndrome are sporadic, which means that it is caused by a new genetic change that occurred randomly, and the parents have no control over this happening.


The diagnosis of Pallister-Hall syndrome is based on the medical history of past symptoms, a family history of parents with Pallister-Hall disorder and suggestive signs listed above on physical examination. A magnetic resonance imaging (MRI) study of the brain will reveal the hypothalamic hamartoma. DNA testing can be performed to look for the altered GLI3 gene, which confirms the diagnosis of Pallister-Hall syndrome. The major difficulty in diagnosing the disease without the genetic test is the wide range and variable severity of symptoms that an individual with Pallister-Hall may manifest.


While there is no cure for Pallister-Hall syndrome, recent advances in medicine have made vast improvements in treating children with the disease. It is important to monitor the size, shape, and location of the hypothalamic hamartoma to know if tumor growth will cause undue problems. If necessary, a surgical procedure can be done to remove it. A shunt can also be placed in the brain to drain the cerebrospinal fluid thus relieving the hydrocephalus. Hormone replacement therapy can treat the pituitary dysfunction. Orthopedic surgery can be done to correct skeletal finger and toe abnormalities. Affected parents or those with a child born with Pallister-Hall syndrome may want genetic testing prior to future pregnancies or an amniocentesis with a current pregnancy.


The prognosis for people with Pallister-Hall syndrome depends on the severity of the disease. The infants succumbing to an early death are most likely due to severe abnormalities of the respiratory system, large hypothalamic hamartomas, and complex, difficult to correct abnormalities of the pituitary system. In the absence of life-threatening malformations and early treatment for medical symptoms, the prognosis for a healthy normal life is quite excellent.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.


Pallister-Hall Foundation (Australia)
Very good website with extensive information including a dictionary of important terms. Also has multiple links to sites and information about current research.

University of California, San Francisco, Neuroradiology
Various radiological images of the brain, hands, feet associated with Pallister-Hall

National Human Genome Research Institute
Nice government website with information on diagnosis, medical evaluation, symptoms

Genetic Disorders
Informative website on genetic disorders.

United States National Library of Medicine
Lists the major characteristics of the disease, but doesn’t provide other information.

Google Search for Pallister-Hall Syndrome

References and Sources

Nussbaum R, McInnes R, &Willard H (2001). Thompson & Thompson Genetics in Medicine, 6th ed. W.B. Saunders Company. p. 243-244. Pallister-Hall Foundation (Australia) Online Mendelian Inheritance of Man