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Rebecca E. Rosenberg, MD, MPH; J. Kiely Law, MD, MPH; Gayane Yenokyan, MS; John McGready, PhD; Walter E. Kaufmann, MD; Paul A. Law, MD, MPH

Arch Pediatr Adolesc Med. 2009;163(10):907-914.

Objectives  To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis.

Design  Cross-sectional study.

Setting  Internet-based autism registry for US residents.

Participants  Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin.

Main Exposures  Zygosity and sex.

Outcome Measures  Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening.

Results  Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases.

Conclusions  Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid.

Author Affiliations: Department of Medical Informatics (Drs Rosenberg, J. K. Law, and P. A. Law) and Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute (Dr Kaufmann), The Johns Hopkins Medical Institutions; Departments of Pediatrics (Drs J. K. Law and P. A. Law) and Psychiatry, Neurology, Pathology, and Radiology (Dr Kaufmann), The Johns Hopkins University School of Medicine; and Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University (Ms Yenokyan and Dr McGready), Baltimore, Maryland.

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