Pallister-Hall Syndrome

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Pallister-Hall syndrome


Pallister-Hall syndrome is an extremely rare developmental disorder marked by a spectrum of features ranging from mild (extra fingers or toes or a non-cancerous malformation in the hypothalamus region of the brain) to severe (laryngotracheal cleft, an opening between the windpipe and voicebox that can cause death in newborns).


First reported in 1980 by American geneticist Judith G. Hall and American medical doctor Philip D. Pallister, Pallister-Hall syndrome is often diagnosed at birth. Some symptoms are immediately noticeable, including short limbs, extra digits, unusual facial features, or blockage of the anal opening. Some signs, such as mental retardation and abnormalities of the heart, lung, or kidneys, must be diagnosed by a physician.

Newborn infants with Pallister-Hall syndrome must be carefully watched for signs of hypopituitarism (insufficient production of growth hormones by the pituitary gland), which can cause fatal complications if not promptly treated. Similarly, inadequate activity of the adrenal gland can be lethal in newborns. If not immediately recognized, an imperfectly formed anus can also develop serious complications in a newborn. Because of its sometimes-serious consequences, Pallister-Hall syndrome is considered part of the CAVE (cerebro-acro-visceral early lethality) group of disorders.

This syndrome is also known by a variety of alternative names, including congenital hypothalamic hamartoblastoma, hamartopolydactyly syndrome, hypothalamic hamartoblastoma syndrome, Hall syndrome 2, hypothalamic hamartoblastoma-hyperphalangeal hypoendocrinehypoplastic anus (4H) syndrome, hypothalamic hamartoblastoma-hypopituitarism-imperforate anus-postaxial polydactyly syndrome, microphallus-imperforate anus-syndactyly-hamartoblastoma-abnormal lung lobulationpolydactyly (MISHAP) syndrome, and renal-anal-lungpolydactyly-hamartoblastoma (RALPH) syndrome).

Genetic profile

Pallister-Hall syndrome is believed to have autosomal dominant inheritance , meaning that it can occur in either sex, and is passed from generation to generation when an abnormal gene is received from one parent and a normal gene is received from the other. Affected patients have a 50% chance of passing the disorder to each offspring. In most such cases, signs and symptoms in affected offspring are similar to those of the parents. However, Pallister-Hall syndrome is more commonly found in isolated cases involving individuals with no family history of the disorder. These cases are thought to result from new, random, genetic mutations with no known cause. The gene responsible is GL13 (chromosomal locus 7p13). Because of the rarity of this disorder and the subtlety of its identifying characteristics, the ratio of these random mutation cases to inherited cases is not known.


As of early 2001, only about 100 cases of this very rare genetic disorder were known. Males are believed affected by Pallister-Hall syndrome about twice as often as females. The disorder is not limited to particular ethnic groups. Some researchers have proposed that many patients with Pallister-Hall signs and symptoms have been misdiagnosed as having a related genetic disorder, isolated post-axial polydactyly type A (PAP A). It should be noted that Pallister-Hall has only been known since 1980, and that the syndrome's full spectrum is still being investigated. As this spectrum expands, greater numbers of milder cases are being uncovered.

Signs and symptoms

This disorder is noted for a wide range of signs and symptoms, including the following:

  • Abnormalities of the head, neck, and facial areas including short neck, short midface, flat nasal bridge, small tongue, noticeable underdevelopment of one jaw compared to the other, asymmetric skull, cleft palate and other irregularities of the palate, cleft larynx or epiglottis, cysts on the gums, and ears that are small, low-set, and abnormally rotated toward the back of the head.
  • Hypothalamic hamartoblastoma, a non-cancerous tumor in the hypothalamus. It grows at the same rate as nearby brain tissue, up to 4 cm across, taking the place of the hypothalamus. Most hypothalamic hamartomas have no symptoms, but in some cases they can cause neurological problems including gelastic epilepsy , which causes chest and diaphragm movements similar to those that occur during laughter.
  • Inhibited flow of cerebrospinal fluid in the brain.
  • Limb abnormalities including short limbs, extra fingers or toes (central or postaxial polydactyly), webbing of fingers or toes (syndactyly), abnormally small fingernails or toenails, or absent nails.
  • Respiratory abnormalities including underdeveloped or abnormally developed lungs.
  • Anus lacking the usual opening.
  • Congenital heart defects.
  • Kidneys with abnormal development or placement.
  • Underdeveloped or abnormally developed adrenal, pituitary, or thyroid glands. This can lead to decreased activity of these glands. Some Pallister-Hall newborns cannot survive due to insufficient activity of the adrenal gland. An underdeveloped pituitary gland can also have lethal consequences. Symptoms of hypopituitarism may include hypoglycemia, jaundice, or unusual drowsiness.
  • In males, unusually small penis, underdeveloped testicles, or failure of one or both testes to descend normally.
  • Retarded growth in most patients.
  • Mild mental retardation.
  • Spinal abnormalities.
  • Dislocated hips.
  • Signs of puberty may appear unusually early.


Both clinical examination and family history are used to diagnose Pallister-Hall syndrome.

The hallmark clinical findings are hypothalamic hamartoma (a non-cancerous tumor in the hypothalamus), as well as extra fingers or toes. Another sign useful for diagnostic purposes is bifid epiglottis, a cleft in the thin flap of cartilage behind the base of the tongue. This particular malformation is almost never seen except in cases of Pallister-Hall syndrome. It rarely causes problems.

Prenatal testing may be conducted by ultrasound, however its effectiveness in detecting Pallister-Hall syndrome is not conclusive.

A molecular genetic test exists to scan the coding regions of the GL13 gene for mutations, but as of early 2001 such testing was available only for scientific research purposes.

Treatment and management

Management will depend on the specific signs and symptoms present.

Unless there are unusual complications, hamartoblastomas are usually left in place. However, it is sometimes necessary to surgically remove a hamartoblastoma when it causes undue pressure on the brain (hydrocephalus ). Hamartoblastomas are usually monitored throughout the life of the patient. Typically, magnetic resonance imaging (MRI) is used, because hypothalamic hamartomas are sometimes not visible on computerized tomography (CT) scans or cranial ultrasound examinations.

Because of the dangers posed by adrenal insufficiency, Pallister-Hall patients will often be assessed for cortisol deficiency. Cortisol (hydrocortisone) is an important steroid hormone released by the adrenal glands. Patients are also likely to see an endocrinologist to evaluate their growth hormone, luteinizing hormone, follicle-stimulating hormone, and thyroid hormone levels. X rays may be taken of limbs, and the kidneys may be examined by ultrasound. The epiglottis may be examined by laryngoscope, an instrument used to view the larynx through the mouth.

If patients show evidence of aspiration (when breathing forces foreign matter into the lungs) they should be seen immediately by an ear, nose, and throat specialist to determine whether laryngotracheal cleft is present.

Newborns with hypopituitarism should immediately be given hormonal replacement therapy and watched closely for life-threatening complications.

A surgical procedure known as a colostomy may be needed to correct an imperforate anus.

Similarly, extra toes or fingers can be surgically corrected on an elective basis.

Seizures, such as those caused by gelastic epilepsy, may also require symptomatic treatment.

Whenever a new case of Pallister-Hall syndrome is uncovered, it is advisable to also examine the parents and any offspring for the disorder. Evaluation for a parent is likely to include a cranial MRI, x rays of hands and feet, and laryngoscopy.

At the time of writing in early 2001, the U.S. National Human Genome Research Institute was seeking to recruit between 50 and 100 Pallister-Hall patients for a comprehensive study of the severity, natural history, origins, and other aspects of the syndrome. Researchers there intend to investigate the relationship between Pallister-Hall and some disorders with similar characteristics, including Greig cephalopolysyndactyly syndrome (GCPS), McKusick-Kaufman syndrome (MKS), Bardet-Biedl syndrome (BBS), and oro-facial-digital syndromes (OFDs). No special drugs or other treatments were to be used in this study.


Because of the broad range and severity of Pallister-Hall signs and symptoms, the prognosis varies widely from case to case.

In families in which multiple cases of Pallister-Hall syndrome exist, the prognosis for any new case is likely to be similar to the existing cases. Mild forms of the syndrome have been identified in a number of large, healthy families believed to have a normal life expectancy.

In cases that occur in isolated individuals, the prognosis is based on the specific malformations present. Reviews of these malformations as reported in scientific literature have limited usefulness because published cases tend to be more severe than those normally encountered. Unless there are life-threatening malformations such as hypopituitarism, the prognosis for these random cases is considered excellent.

There is a 50% chance that any child of a Pallister-Hall patient will be affected.



Pallister-Hall Foundation. RFD Box 3000, Fairground Rd., Bradford, VT 05033.

Patient Recruitment and Public Liaison Office. Building 61, 10 Cloister Court, Bethesda, Maryland 20892-4754. (800) 411-1222.


Biesecker, Leslie G., MD. "Pallister-Hall Syndrome." [May 24, 2000]. GeneClinics. University of Washington, Seattle. <>.

"Pallister-Hall syndrome." NORD—National Organization for Rare Disorders.

"Pallister-Hall syndrome." United States National Library of Medicine. <>.

David L. Helwig