Social communication skills profile in infants with sex chromosome trisomy at 12 months of age

Abstract

Sex Chromosome Trisomy (SCT) conditions are genetic disorders that affect approximately 1:500 children. Although there is considerable variability in phenotype, individuals with SCT have an elevated likelihood, compared to the general population, of developing social deficits and autism spectrum disorder (ASD). Studies report that 10–35 % of individuals with SCT meet criteria for ASD, depending on differences in ascertainment methods and diagnostic criteria. More specifically, ASD prevalence has been estimated at approximately 18 % (range 10–27 %) for XXY, 15 % (10.8–20 %) for XXX, and 30 % (19–43 %) for XYY.^. Understanding social development in young children with SCT is important for identifying potential early predictors of later ASD diagnoses and informing early intervention efforts and specific targets for intervention. We describe the social communication profiles of 69 participants with a prenatal diagnosis of SCT (XXY/Klinefelter syndrome=45, XYY=12, and XXX=12) participating in a prospective natural history study at 12 months of age. All participants completed the Autism Diagnostic Observation Schedule- 2nd edition (ADOS-2) Toddler Module (TM) and the Bayley Scales of Infant and Toddler Development- 3rd edition (Bayley-III) associated with their 12-month visit. Supplementary analyses of the impact of wearing masks during COVID19 are included. Participants showed elevated scores on ADOS-2 TM language/ social communication and reciprocal social interaction items including use of gestures, directed babbling/vocalizations towards others and in skills related to initiating social interactions and directing facial expressions toward others. Participants showed few difficulties on items that measured restricted and repetitive behaviors (RRBs). There were no significant differences between SCT subtypes. Lower receptive and expressive language scores on the Bayley-III correlated with more challenges (higher scores) as measured by ADOS-2 TM clinical severity scores. Results show that children with SCT conditions as young as 12 months of age are at increased likelihood for social communication deficits. They also show few RRBs, differentiating them from young children diagnosed with idiopathic ASD. While 45 % had scores in the mild concern range or above, no participants received a clinical diagnosis of ASD. Prospective follow-up of this cohort will detail the developmental profile of social communication skills beyond 12 months of age and identify the proportion and early predictors of those who emerge to meet criteria for a clinical diagnosis of ASD. Results support close monitoring of early social development and provide specific early social development skills to target in future early intervention trials in infants with SCT.