Tackling defective Prefrontal development in Mendelian Syndromes: a compelling (pre-) clinical integrative approach

Rare Genetic Neurodevelopmental Syndromes (RGNS) are frequently accompanied by
developmental and behavioural problems and have a negative effect on the
quality of life in the patients and their caregivers. Syndrome management
currently mainly focuses on somatic characteristics. However, diagnosis and
intervention targeting abnormal behaviour, neurocognitive dysfunctioning and
psychopathology may very well improve quality of life and long term outcome. In
this study, we will focus on five RGNS, namely Witteveen-Kolk Syndrome
(WitKoS), Coffin-Siris Syndrome (CSS), KBG syndrome, FOXP1 syndrome (FOXP1S),
Brunner syndrome and Wiedemann*Steiner Syndrome (WSS), because of preliminary
evidence for abnormal behaviour, neurocognitive dysfunction and associated
psychopathology.

First, to define individual as well as group based neurocognitive,
psychopathological and behavioural profiles for the RGNS of interest. Second,
to develop and evaluate tailor-made interventions that target behavioural
problems, psychopathology and quality of life in these RGNS. Third, to create
an overview of the applicability of a set of validated, neurocognitive and
behavioural tests adapted to RGNS. Fourth, to identify factors that predict
effect of the intervention.

This study is primarily an observational cross-sectional study and uses
secondary between-subject design to define group based characteristics as well
as a within-subject design to evaluate tailor-made interventions.

The tailor-made, non-medical intervention is designed by an experienced
multidisciplinary intradisciplinary team, constitutes the regular course of
action after diagnoses, also known as standard practice and is targeted at the
patient and/or caregivers. It consists of the formulation of treatment goals,
psycho-education based on the strength-weakness profile and specific
interventions targeting the treatment goals. These interventions are derived
from behavioral therapy, cognitive behavioral therapy, acceptance and
commitment therapy, Eye Movement Desensitization and Reprocessing and systemic
therapy. Treatment will span 7 to 11 sessions of 45 minutes, with a maximum of
one session per week and is completed after evaluation at N=1-level.
After completion of personalised patient-focused treatment, a parent-focused
treatment will be offered to parents of participants <18
years old with RGNS. The treatment will be offered when parents still report a
high lever of behavioural problems after the individualised treatment of the
child or when they report high levels of parental stress. This treatment
consists of 5 to 11 group sessions of 90 minutes.

This study can only be executed in this patient population, by its nature
consisting of children and incapacitated adults. All tests and methods used are
non-invasive, and all procedures that subjects need to undergo are classified
as *procedures with minimal risk and burden* according to the guideline
*Toetsing van onderzoek met Minderjarige proefpersonen*.