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Mol Autism. 2019 Jul 16;10:30. doi: 10.1186/s13229-019-0281-5. eCollection 2019.

Neuropsychiatric phenotypes and a distinct constellation of ASD features in 3q29 deletion syndrome: results from the 3q29 registry.

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1Genetics and Molecular Biology, Laney Graduate School, Emory University, Atlanta, USA.
2Department of Human Genetics, School of Medicine, Emory University, Atlanta, USA.
3Department of Pediatrics, School of Medicine, Emory University, Atlanta, USA.
4Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, USA.
5Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA.
Whitehead 305M, 615 Michael Street, Atlanta, GA 30322 USA.



The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described.


We ascertained individuals with 3q29 deletion syndrome (3q29Del, "cases," n = 93, 58.1% male) and typically developing controls (n = 64, 51.6% male) through the 3q29 registry ( Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n = 48 cases, 56 controls), Social Communication Questionnaire (n = 33 cases, 46 controls), Autism Spectrum Screening Questionnaire (n = 24 cases, 35 controls), and Achenbach Behavior Checklists (n = 48 cases, 57 controls).


3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p < 2.2E- 16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR = 41.8, p = 4.78E- 05) than in males (OR = 24.6, p = 6.06E- 09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRS T-score = 71.8, control SRS T-score = 45.9, p = 2.16E- 13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p = 0.001), which is mirrored by elevated mean scores on the Achenbach diagnostic and statistical manual-oriented sub-scales (p < 0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation.


Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD.


3q29 deletion; Autism; Copy number variants; Developmental delay; Genomic disorder; Psychiatric genetics; SRS

Conflict of interest statement

Competing interestsCAS reports receiving royalties from Pearson Clinical for the Vineland-3. The other authors declare that they have no competing interests.

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