Autism in Klinefelter Syndrome (47,XXY)

Background Klinefelter Syndrome (KS;47,XXY) is associated with a range of neurodevelopmental and psychiatric outcomes, including higher autism rates. There is limited information regarding associations between autism diagnoses and clinical presentation profiles in KS: a gap with important implications for our understanding and care for autism and KS. Methods We compared KS individuals with and without autism (KS-Aut;N=37, and KS-NoAut;N=53, respectively) aged 6–25 years for clinical outcomes including: multiple measures of autism-related symptoms; adaptive functioning; psychopathology; and executive functioning. Autism diagnostic status in KS was determined using ADI-R and ADOS-2 assessments in all KS individuals within a DSM-5 framework. Results The autism diagnosis rate in KS was 41%(N=37/90). Autism symptoms were higher in the KS-Aut group than the KS-NoAut group, but with substantial overlap in symptom distributions between groups - especially for sensory differences. Moreover, autism symptoms were elevated for many within the KS-NoAut group. Comparison of autism symptomatology between the KS-Aut group and a non-syndromic sample of autistic individuals (ClinAut) highlighted fewer autistic symptoms in the KS-Aut group on nonverbal communication and repetitive behaviors/speech, but more sensory differences. The KS-NoAut group had significantly better adaptive functioning than the KS-Aut group, but both groups obtained lower scores relative to the normative sample. Psychopathology was significantly higher in the KS-Aut vs. KS-NoAut group for the CBCL Thought Problems scale. Executive functioning (EF) was impacted in both groups, with a relative sparing of EF behavioral regulation scales in the KS-NoAut group. Limitations The KS cohort studies cannot be assumed to represent all KS individuals. Comparisons on the KS-Aut and ClinAut groups are preliminary given the lack of prospective matching for age and cognitive ability. Conclusions Autism is highly prevalent in KS, though autistic differences may manifest differently relative to individuals with idiopathic autism. Many features show poor differentiation between autistic and non-autistic individuals with KS. Presence of autism in KS is associated with differences in adaptive functioning, psychopathology, and executive functioning. Thus, autism screening and evaluation in KS is extremely important to ensure appropriate access to necessary interventions.