Pallister–Hall syndrome

Pallister–Hall syndrome (abbreviated PHS)[1] is a disorder that affects the development of many parts of the body.

Pallister–Hall syndrome (PHS)
Pallister–Hall syndrome is inherited in an autosomal dominant pattern.
SpecialtyMedical genetics 

It is named for Judith Hall and Philip Pallister.[2][3]

Presentation

Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma 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, an obstruction of the anal opening (imperforate anus), and kidney 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 (a small but extremely important structure deep in the centre of the brain), the temporal lobes and the frontal lobes. If the child has gelastic seizures and precocious puberty, 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 gene provides instructions for making a protein that controls gene expression, 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.

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 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.

Notable Cases

References
  1. https://rarediseases.info.nih.gov/diseases/7305/pallister-hall-syndrome
  2. synd/506 at Who Named It?
  3. Hall JG, Pallister PD, Clarren SK, et al. (1980). "Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly--a new syndrome? Part I: clinical, causal, and pathogenetic considerations". Am. J. Med. Genet. 7 (1): 47–74. doi:10.1002/ajmg.1320070110. PMID 7211952.
  4. https://www.qt.com.au/news/man-life-threatening-disorder-needs-nbn-its-joke/3204152/
  5. https://www.youtube.com/watch?v=AZGwNBguEl0&t=51s
  6. https://drive.google.com/file/d/1OmvV07NoZo-oygxIjqMwncKfc6DL4htW/view
Classification
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.