Understanding Behavior in Phelan-McDermid Syndrome

Abstract

Background: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare genetic disorder characterized by developmental delay, hypotonia and severely delayed speech. Behavioral difficulties are often reported in PMS, although knowledge of behavioral profiles and the interpretation of reported behavior remains limited. Understanding the meaning of behavior requires considering the context as well as other domains of functioning, for example the individual's level of cognitive, social and emotional development. Combining structured direct in-person neurodevelopmental assessments with contextual assessments to enable meaningful interpretations of reported behavior on functional dimensions across multiple units of analysis, as proposed by the RDoc framework, is essential.

Methods: In this article we present a structured multidisciplinary method of assessment through direct in-person neurodevelopmental assessments and assessment of contextual factors. Our study sample includes data of 33 children with an average age of 6.2 years (range 1.1 to 15.7) with PMS, obtained through individual in-person assessments in combination with parent informed questionnaires. We assessed developmental age using the Bayley-III, adaptive behavior was assessed with the Vineland screener, social-emotional development with the ESSEON-R and behavior by using the CBCL.

Results: Our results show a great deal of variability in phenotypic presentation with regard to behavior, symptom expression and symptom severity in individuals with PMS. The data on behavior is interpreted in the context of the individual's level of cognitive, adaptive development and the (genetic) context. Behavioral data showed high levels of withdrawn behavior and attention problems. More than half of the children showed borderline or clinical symptoms related to Autism Spectrum Disorder (ASD).

Conclusions: The interpretation of the meaning of certain behavior in PMS is often based on questionnaires and descriptions without taking the specific context of development into account. Combining questionnaires with direct in-person assessments measuring different domains of functioning should be considered a more accurate method to interpret the meaning of findings in order to understand behavior in rare genetic disorders associated with developmental delay such as PMS. Direct in-person assessment provides valuable and specific information relevant to understanding individual behavior and inform treatment as well as increase knowledge of the neurodevelopmental phenotype in individuals with PMS. More specific application of the proposed frameworks on behavior in PMS is desirable in making useful interpretations.

Keywords: 22q13 deletion syndrome; Phelan-McDermid syndrome; behavioral difficulties; contextual assessments; intellectual disability; neurodevelopmental phenotype.

Figure 1

Average (bold line) and individual behavior profiles on the Vineland for (A) the whole sample and for subgroups based on (B) calendar age (CA), (C) developmental age equivalent based on cognition scale in the Bayley-III (DAE) and (D) deletion size. COM, communication; SOC, social behavior; DAY, daily skills; MOT, motor skills; ABT, adaptive behavior total score. Please take into account: the average calendar age was 74 months (6.2 years).

Figure 2

Average (bold line) and individual behavior profiles on the CBCL subscales for (A) the whole sample and for subgroups based on (B) calendar age (CA), (C) developmental age equivalent (DAE) in months based on cognition scale Bayley-III and (D) deletion size. Anx, anxiety/depression; Som, somatic; Withdr, withdrawn; Att, attention problems; Agg, aggression.

Figure 3

Average (bold line) and individual behavior profiles on the CBCL DSM problem areas for (A) the whole sample and for subgroups based on (B) calendar age (CA), (C) developmental age equivalent (DAE) in months based on cognition scale Bayley-III and (D) deletion size. Aff, affective problems; Anx, Anxiety; PDD, pervasive developmental disorder; ADHD, attention deficit hyperactivity disorder; ODD, oppositional deviant disorder.

Figure 4

Average (bold line) and individual behavior profiles on the ESSEON-R for (A) the whole sample and for subgroups based on (B) calendar age (CA), (C) developmental age equivalent (DAE) in months based on the Bayley-III cognition scale and (D) deletion size. SOC, social development; EMO, emotional development.

Figure 5

Average (bold line) and individual behavior profiles on the Vineland for children with and without CBCL-scores in the clinical range for pervasive developmental disorder (PDD). COM, communication; SOC, social behavior; DAY, daily skills; MOT, motor skills; ABT, adaptive behavior total score; DAE, developmental age equivalent in months based on Bayley-III cognition scale. Please take into account: the average calendar age was 74 months (6.2 years).