Abstract
BackgroundPhelan-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.MethodsWe 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.ResultsMaximal 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.ConclusionsCognitive, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-016-9150-0) contains supplementary material, which is available to authorized users.
Highlights
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum
We report that the intellectual disability is less striking in younger children with 22q13.3 deletion syndrome than in older children, as relative developmental functioning (DQ) decreases with increasing age
Our results show that the extent of developmental deficiencies in children with 22q13.3 deletion syndrome is highly variable within age groups, suggesting a contribution of factors other than SHANK3 haploinsufficiency to the developmental phenotype
Summary
Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is characterized by global developmental delay, cognitive deficits, and behaviour in the autism spectrum. There are at least 60 children and 30 adults currently diagnosed in the Netherlands based on data supplied by the eight genetic centres in the Netherlands. These numbers are likely to be underestimates due to the non-specific physical features of PMS, but the number of diagnosed individuals has rapidly increased since the introduction of non-targeted microarray techniques in diagnostics. Children with PMS have a global developmental delay with cognitive deficits, behavioural problems in the autism spectrum and mild dysmorphic features. The extensive cognitive and behavioural and physical problems associated with this disorder are a social and emotional challenge for patients and their families
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