Abstract
Pitt–Hopkins syndrome is an emerging neurodevelopmental disorder caused by haploinsufficiency
of the TCF4 gene on chromosome 18q21. It is characterized by severe intellectual disability,
seizures, microcephaly, constipation and a distinctive facial gestalt. Although the
overlapping phenotype of microcephaly, epilepsy, absent speech and constipation represents
a challenge for the differential diagnosis with Angelman syndrome, Rett syndrome and
Mowat–Wilson syndrome, distinctive of Pitt–Hopkins syndrome are breathing abnormalities,
that can occur as either hyperventilation episodes or apnea crises, and a typical
facial dysmorphism, including bitemporal narrowing, squared forehead, deep-set eyes,
peculiar nose conformation, with broad nasal bridge, down-turned nasal tip and flaring
nostrils, typical shape of the mouth, with a tented and M shaped upper lip, and widely
spaced teeth. The occurrence of these signs in variable association of uncoordinated
movements, microcephaly of postnatal onset, eye abnormalities, constipation, epilepsy
and subtle brain abnormalities is highly predictive of a TCF4 mutation, making it possible to plan a genetic test of choice among severe encephalopathies.
Angelman syndrome represents the nosological condition closest to Pitt–Hopkins syndrome.
Keywords
Pitt-Hopkins syndrome -
TCF4
- differential diagnosis
