Pitt-Hopkins syndrome (PTHS).
Incidence
Overall prevalence of PTHS is unknown. PTHS occurs in both males and females and is not limited to any specific ethnic background. PTHS is caused by haploinsufficiency of TCF4 resulting from either a pathogenic variant in TCF4 or a deletion of the chromosome region in which TCF4 is located (18q21.2). Most affected individuals have been simplex cases (i.e., a single occurrence in a family) resulting from a de novo pathogenic variant or deletion. If deletions are found in approximately one third of individuals with PTHS, the frequency of the condition could be as high as 1:11,000.
Clinical Characteristics
Pitt-Hopkins syndrome (PTHS) is characterized by significant developmental delays with moderate-to-severe intellectual disability and behavioral differences, characteristic facial features, and episodic hyperventilation and/or breath-holding while awake. Speech is significantly delayed and most individuals are nonverbal with receptive language often stronger than expressive language. Other common findings are autism spectrum disorder symptoms, sleep disturbance, stereotypic hand movements, seizures, constipation, and severe myopia.
Precipitants
None. There are no attacks nor acute crisis on these patients.
Provocation Tests
None
Diagnostic Procedures
PTHS should be suspected in individuals with developmental delay, moderate-to-severe intellectual disability, behavioral differences, characteristic facial features, and episodic hyperventilation and/or breath-holding while awake. The diagnosis is confirmed by identification on molecular genetic testing of a heterozygous pathogenic variant in TCF4 or a deletion of the chromosome region in which TCF4 is located (18q21.2).