Clinical characteristics: Pallister-Hall syndrome (referred to as PHS in this entry) is characterized by a spectrum of anomalies ranging from polydactyly, asymptomatic bifid epiglottis, and hypothalamic hamartoma at the mild end to laryngotracheal cleft with neonatal lethality at the severe end. Individuals with mild PHS may be incorrectly diagnosed as having isolated postaxial polydactyly type A. Individuals with PHS can have pituitary insufficiency and may die as neonates from undiagnosed and untreated adrenal insufficiency.
Diagnosis/testing: The diagnosis of Pallister-Hall syndrome can be established in a proband with both hypothalamic hamartoma and mesoaxial polydactyly. Identification of a heterozygous pathogenic variant in GLI3 confirms the diagnosis.
Management: Treatment of manifestations: Urgent treatment for endocrine abnormalities, especially cortisol deficiency; management of epiglottic abnormalities depending on the abnormality and the extent of respiratory compromise. Bifid epiglottis, the most common abnormality, typically does not need treatment. Standard treatment of anal atresia or stenosis; symptomatic treatment of seizures; elective repair of polydactyly; developmental intervention or special education for developmental delays.
Prevention of secondary complications: Biopsy or resection of hypothalamic hamartoma may result in complications and lifelong need for hormone replacement; seizures may begin or worsen with use of stimulants for attention deficit disorder.
Surveillance: During childhood, annual developmental assessment and annual medical evaluation to assess growth and monitor for signs of precocious puberty.
Genetic counseling: Pallister-Hall syndrome is inherited in an autosomal dominant manner. Individuals with PHS may have an affected parent or may have the disorder as the result of a de novo pathogenic variant. About 25% of individuals have a de novo pathogenic variant. Persons with a de novo pathogenic variant are generally more severely affected than those with a family history of PHS. The risk to offspring of an affected individual is 50%. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known. The reliability of ultrasound examination for prenatal diagnosis is unknown.
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