Exploration of ASD Symptoms Among Individuals with Pitt-Hopkins Syndrome

Background:  Pitt-Hopkins Syndrome (PTHS) is caused by disruption (mutation or deletion) of transcription factor 4 (TFC4, located on chromosome 18). Haploinsufficiency, or inheriting only one working copy of TCF4, causes PTHS. Approximately, 200-300 documented cases of PTHS exist worldwide. Available clinical studies describe individuals with PTHS as exhibiting some of the core symptoms of Autism Spectrum Disorder (ASD), including difficulties in verbal and nonverbal communication, sensory sensitivity, and social interaction difficulties. Significant developmental delays, including motor delays, and intellectual disability are also reported in individuals with PTHS. 

Objectives:  The current study focused on obtaining specific caregiver-reported descriptions of individuals with PTHS to clarify and characterize the presence of ASD symptoms in this population, with particular emphasis on the social, communication, adaptive, developmental, and repetitive behaviors of individuals with PTHS.

Methods:  Parent/caregiver participants were recruited through the Pitt Hopkins Research Foundation and completed questionnaires over the telephone and by mail, including a detailed demographic and background questionnaire, the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R), Communication and Symbolic Behavior Scales-Infant Toddler Checklist, Repetitive Behavior Questionnaire, Short Sensory Profile-2, and Vineland Adaptive Behavior Scales- II. Additional measures of ASD symptomatology and behavioral difficulties were also obtained. 

Results:  Data are currently available for 18 individuals with confirmed PTHS, including 11 males. The mean age of the individuals with PTHS at the time of the caregiver interview was 7.67 years (range of 2 to 17 years), and adaptive skills were well below average (mean Vineland-II Adaptive Behavior Composite standard score = 47.9, SD = 10.35), indicating developmental delays across skill areas. On rating scales, individuals with PTHS were described as exhibiting delays in early emerging social-communication skills on the CSBS-ITC (mean total raw score = 21.63, consistent with a range of concern for a child at a 10-month level) and the presence of significant ASD “red flags” on a brief screening tool developed for very young children (mean “failed” M-CHAT-R items = 9.73, considered “high risk”). On the RBQ, a tool that has demonstrated good validity in measuring repetitive behaviors in several genetic syndromes as well as ASD, individuals with PTHS received elevated scores for overall repetitive behaviors and in particular, the presence of clinically significant stereotyped behaviors in 83% of the sample (mean SB score = 9.17, SD = 4.33). A range of sensory differences were also endorsed by caregivers on the SSP-2 for their children. Data collection and analyses are ongoing and will provide additional information about relations between variables and will seek to clarify whether level of functioning and/or level of social-communication impairments better predict the ASD symptom profiles of individuals with PTHS. 

Conclusions:  Information regarding ASD symptoms and patterns of behavior within genetic syndromes such as PTHS may be helpful in characterizing a broader ASD phenotype. Further, a better understanding of social communication and behavioral difficulties in individuals with known genetic differences and developmental delays may help guide more informed recommendations for intervention.