Pallister-Hall syndrome is a genetic disorder that affects the development of many parts of the body.
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 of many organs and tissues before birth.
This condition is very rare; its prevalence is unknown. It 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.
Most people with this condition have:
- Extra fingers and/or toes (polydactyly)
- The skin between some fingers or toes may be fused (cutaneous syndactyly)
- An abnormal growth in the brain called a hypothalamic hamartoma
- A malformation of the airway called a bifid epiglottis
- An obstruction of the anal opening (imperforate anus)
- 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.
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. The most common types of seizures that occur are known as Gelastic Epilepsy. Seizures may begin at any age but usually before three or four years of age. The seizures usually start with laughter that 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.
Treatment of individuals with Pallister-Hall syndrome depends on their individual manifestations. Management of epiglottic abnormalities depends on the type of abnormality and extent of respiratory compromise. Treatment for endocrine abnormalities, especially for cortisol deficiency, is urgent. Repair of polydactyly can be undertaken on an elective basis and anal atresia or stenosis treated in the standard manner. Hypothalamic hamartomas should not be removed or biopsied because of the risk of surgical complications and need for hormone supplements during the individual’s remaining life. Gelastic seizures are not responsive to therapy so they are treated symptomatically.