Developmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children.
BACKGROUND
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. Knowledge about developmental and behavioural characteristics of this rare chromosomal disorder is still limited despite a rapid growing number of diagnoses. Our aim was to study a new and relatively large cohort to further characterize the developmental phenotype of children with PMS.


METHODS
We performed a descriptive study of children with a 22q13.3 deletion including SHANK3, aged 8 to 178 months, who were systematically (n = 34) and longitudinally (n = 29) assessed with standardized instruments: Bayley Scales of Infant and Toddler Development, third edition; Wechsler Preschool and Primary Scale of Intelligence, third edition; and Vineland Screener for Social and Adaptive Behavior.


RESULTS
Maximal developmental functioning ranged from 34 to 52 months depending on the developmental domain. In general, children performed poorest in the domain of language and best on the domain of motor (young children) or cognitive development (older children). At the individual level, 25 % scored better for receptive and 18 % for expressive language, whereas 22 % scored better for fine and 33 % for gross motor function. Developmental quotients were higher in younger children and decreased with age for all developmental domains, with 38 % of the children showing no improvement of cognitive developmental functioning. Almost all children (33/34) had significant deficits in adaptive behaviour. Children with very small deletions, covering only the SHANK3, ACR, and RABL2B genes, had a more favourable developmental phenotype.


CONCLUSIONS
Cognitive, motor, and especially language development were significantly impaired in all children with PMS but also highly variable and unpredictable. In addition, deficits in adaptive behaviour further hampered their cognitive development. Therefore, cognitive and behavioural characteristics should be evaluated and followed in each child with PMS to adapt supportive and therapeutic strategies to individual needs. Further research evaluating the relationship between deletion characteristics and the developmental phenotype is warranted to improve counselling of parents.
University of Groningen, University Medical Center Groningen, Department of Genetics, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Renée J
RJ
Zwanenburg
De Kinderacademie Groningen, Centre of Expertise for Child Development Care and Research, Herestraat 106, 9711 GH Groningen, The Netherlands.
Selma A J
SA
Ruiter
Eindhoven University of Technology, Department of Mathematics and Computer Science, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.
Edwin R
ER
van den Heuvel
University of Groningen, University Medical Center Groningen, Department of Pediatrics, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Boudien C T
BC
Flapper
University of Groningen, University Medical Center Groningen, Department of Genetics, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Conny M A
CM
Van Ravenswaaij-Arts
22q13 deletion syndrome; Autism; Developmental phenotype; Intellectual disability; Neurodevelopmental disorders; Phelan-McDermid syndrome; SHANK3