Pallister–Hall syndrome
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Pallister–Hall syndrome (abbreviated PHS) is a disorder that affects the development of many parts of the body. It is named for Judith Hall and
Philip Pallister Philip, also Phillip, is a male given name, derived from the Greek language, Greek (''Philippos'', lit. "horse-loving" or "fond of horses"), from a compound of (''philos'', "dear", "loved", "loving") and (''hippos'', "horse"). Prominent Philip ...
.


Presentation

Most people with this condition have extra fingers and/or toes (
polydactyly Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans ...
), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
called a
hypothalamic hamartoma Tuber cinereum hamartoma is a benign tumor in which a disorganized collection of neurons and glia accumulate at the tuber cinereum of the hypothalamus on the floor of the third ventricle. It is a congenital malformation, included on the spectru ...
is characteristic of this disorder. In many cases, these growths do not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister–Hall syndrome include a malformation of the airway called a bifid epiglottis,
laryngeal cleft A laryngeal cleft or laryngotracheoesophageal cleft is a rare congenital abnormality in the posterior laryngo-tracheal wall. It occurs in approximately 1 in 10,000 to 20,000 births. It means there is a communication between the oesophagus and the ...
, an obstruction of the anal opening (
imperforate anus An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unkno ...
), and
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.


Seizures

As noted above, the hypothalamic hamartoma can cause seizures. The most common types of seizures that occur are known as gelastic epilepsy. The term ''gelastic'' originates from the Greek word "''gelos'' which means "laughter". Seizures may begin at any age but usually before three or four years of age. The seizures usually start with laughter and the laughter is often described as being "hollow" or "empty" and not very pleasant. The laughter occurs suddenly, comes on for no obvious reason and is usually completely out of place. The most common areas of the brain which give rise to gelastic seizures are the
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
(a small but extremely important structure deep in the centre of the brain), the
temporal lobe The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe ...
s and the
frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betwe ...
s. If the child has gelastic seizures and
precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...
, then it is likely that the child will be found to have a hypothalamic hamartoma (a hamartoma in the hypothalamus part of the brain).


Genetics

This condition is very rare; its prevalence is unknown. Mutations in the GLI3 gene cause Pallister–Hall syndrome. The ''
GLI3 Zinc finger protein GLI3 is a protein that in humans is encoded by the ''GLI3'' gene. This gene encodes a protein that belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription f ...
'' gene provides instructions for making a protein that controls
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth. Defects in the same gene also cause
Greig cephalopolysyndactyly syndrome Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more ...
. Mutations that cause Pallister–Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It remains uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister–Hall syndrome. This condition is inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the ''GLI3'' gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.


Diagnosis


Treatment


Notable Cases

*
George William Helon George Helon (born 1965), also known under the pen names George Wieslaw Helon and Jerzy Wieslaw Helon, is an Australian author, businessman, and historian of Polish descent. Helon is on the board of directors of the Polish Nobility Associatio ...
(Australian author and businessman) is a Pallister-Hall Syndrome (PHS) patient, mentor, counsellor and advocate. * Raul Rosas Jr. (UFC fighter) Suffers from Pallister-Hall Syndrome (PHS) https://georgehelon.com/wp-content/uploads/2018/08/George-Helon-Genetic-Support-Network.jpg


References

*


External links


GeneReviews/NCBI/NIH/UW entry on Pallister–Hall Syndrome

Genetics Home Reference
{{DEFAULTSORT:Pallister-Hall Syndrome Rare syndromes Autosomal dominant disorders Transcription factor deficiencies