Pitt-Hopkins syndrome is a rare neurodevelopmental disorder caused by loss of function of one allele of the TCF4 gene. Most cases result from a de novo mutation that leads to a functional loss of one copy of the TCF4 gene. Other cases result from a deletion of the chromosome region in which the TCF4 gene is located (18q21.2).
Pitt-Hopkins syndrome is characterized by distinctive facial features (e.g., deep-set eyes, prominent nose, wide mouth with widely spaced teeth), global developmental delay, and moderate-severe intellectual disability. Breathing problems and epilepsy often occur.
Once Pitt-Hopkins syndrome has been suspected clinically, the diagnosis is confirmed by molecular genetic testing of the TCF4 gene.