Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes

Abstract

Background: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). Methods: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. Results: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. Conclusions: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research.

Clinical and genetic characteristic of patients with Pitt–Hopkins syndrome

“…Дифференциальный диагноз при СПХ следует проводить с синдромами Ангельмана (OMIM 105830), Мовата-Вильсона (OMIM 235730), Ретта (312750), Жубера и синдромом умственной отсталости -гипотоничного лица, Х-сцепленным (OMIM 309580) [2,10,11,14].…”

“…Кроме того для синдрома Ангельмана и СПХ характерны аномалии рефракции и атаксия. Но атаксия при синдроме Ангельмана является одним из ведущих симптомов, и для этого синдрома существуют специфические изменения электроэнцефалограммы [10,11]. При синдроме Мовата-Вильсона характерны специфические мочки ушей, а при СПХ -верхняя губа в виде «лука купидона».…”

“…У больных с СПХ грубые черты лица с выступающей нижней частью, крючковатый нос, диспластичные ушные раковины, верхняя губа в виде «лука купидона» [2,6,10,11]. Для больных с СПХ не характерны грубые пороки центральной нервной системы, описаны дисплазия мозолистого тела, уменьшение гиппокампа, гиперинтенсивность белого вещества височных долей, задержка миелинизации, гипоплазия червя мозжечка, атрофия мозжечка, вентрикуломегалия [6,10].…”

Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome

“…Disease-causing mutations are primarily de novo with rare instances of parental mosaicism (1,2) and result in TCF4 haploinsufficiency or dominant negative mechanisms (3)(4)(5)(6)(7). PTHS patients display features of ASD and are more generally characterized by intellectual disability, developmental delay, breathing abnormalities, absent or limited speech, motor delay, seizure, constipation, and facial features including wide mouth and a broad nasal base with high bridge (8)(9)(10)(11). Exactly how mutations in TCF4 lead to this disorder remains an open question.…”

Pitt-Hopkins syndrome

“…Diagnosis is made using genetic testing in combination with clinical diagnostic criteria based on physical, developmental and psychosocial phenotypical indicators. Caution is advised when diagnosing PTHS due to phenotypic overlap with neurological disorders such as Angelman Syndrome, Rett Syndrome and Cornelia de Lange Syndrome (Watkins et al 2019, Bonello et al 2017. Clinical Features PTHS can lead to a number of dysmorphic physical and skeletal features which include:…”