Pallister-Hall syndrome (PHS) is a rare genetic disorder that can affect many organ systems of the body. It is exceptionally rare and the frequency with which it affects populations is currently unknown. It appears to affect all ethnicities equally. Although the physical features usually are apparent at birth, not all cases will exhibit the same abnormalities and the extent of any internal organ involvement can vary considerably.
Definition & Facts
Since it is a genetic disorder, there are certain physical signs that are characteristics of Pallister-Hall syndrome. The more common of these physical signs can include the following:
- Extra fingers and/or toes (polydactyly)
- Fusion of the skin between at least some fingers and/or toes (syndactyly or webbing)
- Improper or incomplete development of the fingernails and toenails
- A thin membrane that blocks the opening of the anus (imperforate anus).
Other developmental defects that may be present, but not readily obvious except by X-ray studies include an abnormality or brain development known as a hypothalamic hamartoma, facial abnormalities that may involve the upper airway, and abnormally-shaped kidneys.
Symptoms & Complaints
The presence of a hypothalamic hamartoma can result in abnormal or arrested growth, abnormal function of glands such as the thyroid and pancreas that depend on the pituitary gland, and problems with fluid and electrolyte balance. In these cases it may be necessary to administer supplemental doses of hormones such as human growth hormone, insulin, or cortisol in infancy.
Hypothalamic hamartoma has been associated with seizure disorders that can range in severity from easy to control with medication to a life-threatening condition known as status epilepticus. It is also also associated with an equally rare condition known as gelastic seizures, gelastic epilepsy, or “laughing seizures.” In this condition a seizure is immediately preceded by a sudden burst of unexpected activity, usually laughing.
Pallister-Hall syndrome is an autosomal dominant genetic condition, meaning that it can be inherited even if only one parent carries the defective gene.
Specifically, a genetic mutation on the GLI3 gene which is located on chromosome 7 has been identified as the cause of this condition. Sometimes, the genetic mutation responsible for Pallister-Hall syndrome is assumed to be spontaneous in which there is no family history of the disorder. Since Pallister-Hall syndrome is caused by a genetic abnormality, there is no known therapeutic intervention that can prevent the condition.
Diagnosis & Tests
A patient's family history, medical history, and presentation of symptoms will be established as part of the diagnostic process. Regarding symptoms, there are several features of this condition that doctors will assess in order to establish a diagnosis. They include: hypothalamic hamartoma, bifid epiglottis, and polydactyly among others. Magnetic resonance imaging (MRI) is the preferred imaging study to detect hypothalamic hamartoma. Ultrasounds may be conducted to assess any abnormalities of the kidneys. X-rays may be conducted to assess other skeletal abnormalities. Laryngoscopy may be conducted to assess any abnormalities of the epiglottis.
Molecular genetic testing can help establish the presence of genetic mutations. Blood tests may be conducted to establish the presence of a cortisol deficiency as well as growth hormone levels and follicle-stimulating hormone (FSH). Prenatal diagnostic processes can involve genetic testing the fetus and prenatal ultrasound to detect polydactyly.
Treatment & Therapy
Treatment in Pallister-Hall syndrome will be determined by the extent of the anatomic abnormalities and their relationship to physiologic changes that they might be expected to cause. Many deformities are asymptomatic. Some structural abnormalities such as extra digits or “webbing” can simply be ignored or repaired using plastic surgery at a later date though occupational therapy may prove to be helpful in assisting patients with how to perform tasks given the presence of hand deformities. Special education may be helpful for patients who struggle with learning disabilities.
Many hypothalamic hamartomas do not grow and may even decrease size as childhood progresses. Only under the rarest of circumstances would surgery be necessary to remove a hypothalamic hamartoma due to how the risk of complications from brain surgery greatly outweighs the therapeutic benefits.
Cortisol deficiency will be treated with replacement therapy. If a seizure disorder develops, it will be managed with conventional anti-seizure medications until an effective drug regimen can be established. Surgery may be performed to address structural problems with the anus. This could include procedures to connect the anus and intestines, a colostomy in which the intestines are routed to a bag outside of the body that is used to collect waste, and an anoplasty which surgically moves the anus.
Prevention & Prophylaxis