Pallister-Hall syndrome (PHS) is a rare genetic disorder that affects many parts of the body, including the hands and feet, brain, airway, kidneys, and anus. Most people with this condition have polydactyly (extra fingers and toes), and the skin between some fingers or toes may be fused (called cutaneous syndactyly). Hypothalamic hamartoma, an abnormal growth in the brain, is characteristic of this disorder. In many cases, these growths do not cause any medical problems. However, some hypothalamic hamartomas lead to seizures or hormonal abnormalities that can be life threatening in infancy. Other features of PHS include bifid epiglottis (a malformation of the airway), imperforate anus (an obstruction of the anal opening), and kidney abnormalities. Although the signs and symptoms of this disorder range from mild to severe, only a small percentage of affected people have serious complications.
PHS is caused by mutations or defects in the GLI3 gene. This gene provides instructions for making the GLI3 protein (also known as zinc finger protein GLI3), which plays a role in limb and brain development.
PHS is inherited or passed down among family members as an autosomal dominant trait. Individuals inherit two copies of most genes, one from the mother and one from the father. To inherit an autosomal dominant trait, only one defective copy of the causative gene must be inherited. Occasionally, PHS occurs in individuals with no family history of the disorder. This is the result of a spontaneous genetic mutation in the egg, sperm cell, or developing embryo. Individuals who acquire PHS as the result of a spontaneous mutation may pass on the mutation to their children. The proportions of those who inherit PHS and those who acquire the syndrome as the result of a spontaneous mutation are not known.
PHS is extremely rare, with about 100 known cases worldwide. The exact prevalence of the syndrome is unknown. PHS does not appear to affect any one gender or ethnicity more than any other.
There is no cure for PHS. Instead, treatment aims to reduce symptoms and prevent complications. Although it has been suggested that some cases of PHS are severe and cause early death, other research suggests that most individuals with the condition have a mild form, with manageable symptoms and a normal life span. If undiagnosed or misdiagnosed, individuals with a severe form of PHS may die soon after birth, because of abnormal activity of the adrenal glands, which sit on top of the kidneys and are responsible for regulating the stress response through the release of hormones.
CAVE complex, cerebro-acro-visceral early lethality syndrome, cerebroacrovisceral early lethality complex, congenital hypothalamic hamartoblastoma syndrome, GLI3 gene, Hall-Pallister syndrome, hypothalamic hamartoblastoma-hypopituitarism-imperforate anus and postaxial polydactyly, hypothalamic hamartoblastoma syndrome, PHS, zinc finger protein GLI3.