Development, cognition, and behaviour in Pitt-Hopkins syndrome

AIM The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt–Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD). METHOD The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature. RESULTS All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD. INTERPRETATION Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families. Pitt–Hopkins syndrome (PTHS) is characterized by intellectual disability, distinctive facial characteristics, breathing abnormalities, and repetitive behaviours. It is caused by genetic deletions ⁄ mutations resulting in TCF4 haploinsufficiency. To date, some 66 patients with confirmed TCF4 changes have been studied worldwide, mainly investigating somatic and genetic aspects. Early descriptions of PTHS in individuals with intellectual disability emphasized an abnormal breathing pattern, distinctive facial features, and postnatal microcephaly. Further definition of the PTHS phenotype in later publications included severe developmental delays in motor and speech ⁄ language