Familial Pallister-Hall in adulthood

Area of Science:

• Genetics
• Neurology
• Endocrinology

Background:

• Pallister Hall syndrome is a rare autosomal dominant disorder typically diagnosed in infants and children.
• Diagnostic criteria usually include hypothalamic hamartoma, postaxial polydactyly, and a positive family history, but manifestations are variable.

Observation:

• This report details Pallister Hall syndrome diagnosed in adult patients, a 59-year-old man and his 29-year-old daughter.
• Both patients presented with seizures and hypothalamic hamartoma, with a history of polydactyly.
• The man experienced visual changes and bitemporal hemianopsia after head trauma, with a large urine volume but no pituitary dysfunction.

Findings:

• Genetic testing revealed a novel heterozygous single base pair deletion in the GLI3 gene (frameshift mutation) in the daughter.
• Surgery to debulk the hypothalamic hamartoma improved visual field defects and resolved polydipsia in the father.
• Family history revealed multiple affected members across generations with polydactyly and/or seizures.

Implications:

• This case expands the known clinical spectrum of Pallister Hall syndrome to include adult diagnosis.
• The findings underscore the genetic basis of Pallister Hall syndrome, linked to GLI3 gene mutations.
• This report highlights the need for broader diagnostic considerations for Pallister Hall syndrome in adults presenting with neurological and developmental abnormalities.