ASD and Neurodevelopmental Characterization of Youth with XYY Syndrome

Background:  Sex chromosomal aneuploidies are numeric aberrations of X or Y chromosomes; in the case of XYY, an extra Y chromosome is present in males. Epidemiology estimates indicate a rate of XYY in 1/1000 births, although the diagnosis is reported less frequently (Stochholm, Juul, & Gravholt, 2010). Previous studies have found significant autism spectrum disorder (ASD) symptomatology in this population, although rates vary considerably (Margari, Lamanna, Craig, Simone, & Gentile, 2014). Other prominent characteristics previously described include a slightly lower average IQ than the general population, language impairments, learning disabilities, and a variety of psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD) (Bardsley et al.,2013; Bishop et al., 2011; Leggett, Jacobs, Nation, Scerif, & Bishop, 2010). Studies of this condition have thus far not included gold-standard diagnostic instruments for ASD.

Objectives:

The purpose of this study was to report on previous community diagnoses and findings from administration of gold-standard ASD diagnostic instruments in youth with XYY. We also sought to contextualize these data based on cognitive profiles, as well as specific learning disorder (SLD), intellectual disability (ID), and ADHD diagnoses.

Methods:  A sample of 50 males with XYY were enrolled in a phenotypic characterization study. The sample included an age range of 5 to 25 years (mean age=13.25±5.94). Phenotypic characterization included an IQ estimate from a Wechsler intelligence test (WISC-V, WASI or WAIS-IV). Additionally, the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule, second edition (ADOS-2), the Woodcock Johnson Tests of Achievement, fourth edition (WJ-IV), and the Vineland Adaptive Behavior Scales, second edition were administered.

Results:  Previous diagnoses of ASD in community had been made in 36% (n=18). Additionally, based on parent report, 60% (n=30) had a previous diagnosis of ADHD. Preliminary results from 25 participants indicate that while 32% (n=8), and 24% (n=6) met diagnostic criteria on the ADI-R and ADOS-2 respectively, only 16% (n=4) were given a DSM-5 diagnosis of ASD according to results from these instruments combined with clinical judgment and clinician review of DSM-5 criteria. ADOS-2 profiles (module 2, n=1; module 3, n=18; module 4, n=6) are shown in Figure 1. NVIQ was slightly higher than VIQ, with FSIQ falling approximately 1 SD below the population average, and adaptive behavior generally lower than estimated from IQ scores (Table 1). One participant met criteria for ID (FSIQ and Vineland ABC <70). Twenty one participants completed academic testing, and 61.9% (n=13) met for SLD (FSIQ>70 and achievement standard score in at least one area <78).

Conclusions:  This study found a negatively skewed IQ range, and greater deficits in VIQ compared to NVIQ in youth with XYY, consistent with previous findings (Leggett et al., 2010). While community diagnoses of ASD were higher than reports in previous studies, cohort effects may explain some differences, since rates of ASD have increased ubiquitously. While research based categorical diagnoses of ASD were reduced compared to community diagnoses in the current study, symptomatology is present and needs further exploration, especially in light of the cognitive, language and learning profiles in this group.