Executive functions (EF) have been conceptualized as a collection of higher-order interrelated, but independent, cognitive abilities involved in controlling, regulating, and planning goal-directed behaviors when faced with novel tasks and situations in a dynamically changing environment (Friedman and Miyake, 2017; Miyake et al., 2000; Miyake and Friedman, 2012). EFs, such as working memory, mental flexibility, response initiation, inhibition, set-shifting, impulse control, and action monitoring, play a decisive role in the top-down regulation of thoughts, emotions, and behaviors of daily living and disrupted executive functioning might result not only in cognitive difficulties but also in impairments in social, emotional and moral development (Benavides-Nieto et al., 2017; Martins et al., 2016; Riggs et al., 2006; Vera-Estay et al., 2015). Not surprisingly, meta-analytic evidence indicates that EF deficits are pervasive across a wide range of mental disorders (Abramovitch et al., 2021; Snyder et al., 2015) and associated with what is shared across forms of psychopathology, namely p factor, leading to proposals that EF deficits might act as transdiagnostic risk factors for both internalizing and externalizing symptoms (Nelson et al., 2018; Snyder et al., 2019; Sulik and Obradović, 2017). The term p factor was coined by Caspi and colleagues (2014) to refer to a general dimension of psychopathology that represents the top of a hierarchical structure which is characterized by several distinct diagnosis at the lower level, aggregating into two overreaching externalizing and internalizing domains at the medium level, which finally aggregate into one normally distributed dimension of psychopathology: p.

A growing body of research identifies impairments of EFs as relevant for explaining behavioral differences in individuals affected by genetic and neurodevelopmental conditions, elucidating possible pathways from genetic disorder to behavioral phenotypes via atypical brain development and interaction with the environment (Nelson et al., 2017; Perry et al., 2022; Tsermentseli et al., 2018; Waite et al., 2015; Woodcock, Oliver & Humphreys, 2009).

EF difficulties have long been considered a core feature of the neuropsychological profile of autism spectrum disorder (ASD), accounting for a significant portion of the social-communicative and behavioral outcomes (Damasio and Maurer, 1978; Geurts et al., 2014; Kenworthy et al., 2008; Rumsey, 1985). Further support to this statement was given by the “executive control dysfunction” theory (Ozonoff, 1995; Pennington and Ozonoff, 1996) which points out that deficits in the executive control system generate a set of problems in individuals with ASD, including poor flexibility in behavior, perseveration with maladaptive strategies, inability to learn from mistakes turning into repetitiveness of wrong responses, as well as stimulus overselectivity described by the tendency to respond to only a subset of environmental cues during learning situations that might impair the construction of social cognition (Corbett et al., 2009; Ozonoff et al., 1991; Russell, 1997; Turner, 1997). Moreover, the overselectivity on details is also explained by the “weak central coherence” theory (Frith and Happé, 1994) and by neuronal evidence of intra-cerebral areas overconnectivity and inter-cerebral areas ipoconnectivity (Geschwind and Levitt, 2007). The study by Tsermentseli and colleagues (2018) highlighted a global executive dysfunction profile in patients with ASD and intellectual disability (ID), with the most prominent deficits occurring in set-shifting that predict social impairments and low adaptive skills. Similarly, the same outcomes have been found to be associated with compromised flexibility and planning abilities (Gilotty et al., 2012; Panerai et al., 2014; Wallace et al., 2016); whereas repetitive and stereotyped behaviors, as well as restricted interests, seem to be better justified by deficits in shifting, working memory and response inhibition that gives reason to the “stuck-in-set” perseveration attitude of these individuals (Roelofs et al., 2015; Sayers et al., 2011; South et al., 2007).

Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome (RSTS) are two rare and pluri-malformation genetic syndromes characterized by variable degrees of ID and idiosyncratic manifestations of autistic traits which lend support to the controversial debate about the dissociation of the triad of impairments in ASD proposed by Happe and Ronald in 2008, as CdLS is characterized by greater impairments in socio-communicative skills (Moss et al., 2012; Srivastava et al., 2014), whereas RSTS by the presence of major atypia on the motor level with stereotypies, mannerisms, repetitive and unusual behavioral patterns (Galéra et al., 2009).

Studies addressing individuals affected by CdLS have shown that deficits in the executive functions of planning, working memory, rule switch, and inhibition are responsible for a lower verbal production capacity in conditions that require initiative to start a conversation, with consequent significant impairments in the ability to establish effective interpersonal dynamics (Nelson et al., 2017; Reid et al., 2017). In RSTS, instead, working memory deficits, difficulties in set-shifting, inhibition, as well as lack of mental flexibility, have been linked to behavioral and speech repetitiveness (Perry et al., 2022; Waite et al., 2015, 2023).

There is also mounting evidence that executive dysfunction may underpin behavioral, emotional, and cognitive patterns in a wide range of psychiatric conditions, either characterized by internalizing symptoms, such as obsessive-compulsive disorder (Lawrence et al., 2006; Lopez et al., 2005; Lysaker et al., 2009), anxiety and depressive disorders (Han et al., 2015; Nelson et al., 2018), or by externalizing symptoms like conduct disorder, Attention Deficit and Hyperactivity Disorder (ADHD), and oppositional and defiant disorder (Oosterlaan et al., 2005; Sulik and Obradović, 2017).

Both genetic syndromes involved in this study (CdLS and RSTS) are characterized by developmental trajectories of behavioral phenotype that encounter internalizing and externalizing symptoms, expected to arise and worsen with growth (Ajmone et al., 2022; Cochran et al., 2019; Kline et al., 2018; Yagihashi et al., 2012). However, there is a paucity of research examining how deficits in executive functioning might contribute to the onset of such impairments.

Therefore, this study aims to investigate the role of executive functions in the onset of internalizing and externalizing symptoms, as well as autism-related traits, in children with CdLS and RSTS.

The achievement of these goals will contribute to helping clinicians to draw up proper standards of assessment turning into target age-related interventions aimed at providing personalized healthcare and improving the quality of life of those children. Moreover, it will contribute to a better understanding of potential precursors of later impairments which might pave the way for the onset of psychiatric comorbidities in these syndromes.