Pallister–Hall syndrome (PHS) is a rare genetic disorder that affects various body systems. The main features are a non-cancerous mass on the hypothalamus ( hypothalamic hamartoma) and extra digits ( polydactylism). The prevalence of Pallister-Hall Syndrome is unknown; about 100 cases have been reported in publication.

History

The syndrome was originally described by American and Canadian geneticist
Philip Pallister
and Judith Hall in their research of newborn deaths due to pituitary failure. Subsequent discovery of living children and adults expanded the understanding of the syndrome and established the transmission pattern within families.

Presentation

The main characteristics of the syndrome are extra fingers and/or toes (

polydactyly Polydactyly is a birth defect that results in extra fingers or toes. The hands are more commonly involved than the feet. Extra fingers may be painful, affect self-esteem, or result in clumsiness. It is associated with at least 39 genetic mut ...

), with the skin between some fingers or toes potentially fused or "webbed" (cutaneous syndactyly), and a benign mass or lesion in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

called a hypothalamic hamartoma. This benign tumor may not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities. Other features of Pallister–Hall syndrome include a split opening of the airway called bifid epiglottis, laryngeal cleft, blockage 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 unknow ...

), and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

abnormalities. Signs and symptoms of this disorder vary from mild to severe.

Seizures

The most common type of seizure from this disorder of that occur is known as gelastic epilepsy or "laughing" seizures. Seizures may begin at any age but usually before three or four years of age. The seizures usually start with laughter described as being "hollow" or "empty" and unpleasant. The laughter occurs suddenly for no obvious reason and is often out of place. Other traditional seizure types such as tonic-clonic and

absence seizure Absence seizures are one of several kinds of generalized seizures. Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). Absence ...

s may also develop due to

temporal lobe epilepsy In the field of neurology, temporal lobe epilepsy is an enduring brain disorder that causes unprovoked seizures from the temporal lobe. Temporal lobe epilepsy is the most common type of focal onset epilepsy among adults. Seizure symptoms and b ...

. People with Pallister-Hall may experience less severe seizures than people with a hypothalamic hamartoma only.

Transmission

Pallister-Hall Syndrome occurs due to a mutation in the '' GLI3'' gene that overrides normal genetic development. Before birth the '' GLI3'' gene delivers directions for protein creation that turns on or off development of cells that produce organs and tissues. The abnormal GLI3 gene is shortened and can only turn off targeted genes. Pallister-Hall Syndrome is transmitted in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

pattern. One copy of the altered gene in each cell is sufficient to cause the disorder. Thus, the child of one parent with PHS would have a 50% chance of inheriting the gene that causes the syndrome. Some cases can still result from new mutations in the gene and occur in people with no history of the disorder in their family.

Diagnosis

Central characteristics of the disorder include polydactyly (extra digits on limbs) with possible cutaneous syndactyly (fusion or webbed skin between some fingers or toes) and a hypothalamic hamartoma, a rare brain lesion on the hypothalamus that is present at birth. While the mass may occur unrelatedly, the presence of polysyndactyly warrants investigation for PHS. Currently, clinical diagnosis is through a brain MRI and genetic sequencing for GLI 13 gene, which is known to cause Pallister-Hall Syndrome, as well as Greig cephalopolysyndactyly syndrome. Genetic testing can find and identify the corresponding disorder.

Treatment

Treatment is limited to physical signs and symptoms of the hypothalamic hamartoma. Surgery may be required at birth to fix imperforate anus and address endocrine abnormalities. Selective removal of extra digits may occur in early childhood. Parents and medical practitioners should monitor for signs of endocrine disruption in sleep, eating, or hormonal issues, such as precocious puberty caused by the hypothalamic hamartoma. Seizures may be treated with anticonvulsants. However, gelastic seizures are often intractable and may not benefit from such therapy. Resection of the hypothalamic hamartoma has improved seizure control and hypothalamic function in some patients.

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 Diseases named after discoverers