Background 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. Methods 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 (https://3q29deletion.patientcrossroads.org). 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). Results 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. Conclusions 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.

中文翻译：

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3q29缺失综合征中的神经精神病学表型和独特的ASD特征星座：3q29注册表的结果。

背景1.6 Mb 3q29缺失与神经发育和精神病学表型相关，包括自闭症谱系障碍（ASD）风险增加和精神分裂症风险增加20至40倍。然而，缺失的表型光谱，特别是关于ASD的，仍然描述得很差。方法我们通过3q29注册表（https://3q29deletion.patientcrossroads.org）确定了患有3q29缺失综合症的个体（3q29Del，“病例”，n = 93，男性占58.1％），并且典型地发展了对照组（n = 64，51.6％男性）。 ）。评价了93例神经精神疾病的自我报告。参与者的亚组通过社交反应量表（SRS，n = 48例，56个对照），社会沟通问卷（n = 33例，46个对照）进行了评估，自闭症频谱筛查问卷（n = 24例，35个对照）和阿亨巴赫行为清单（n = 48例，57个对照）。结果3q29Del病例报告的自闭症诊断患病率高于一般人群（29.0％vs. 1.47％，p <2.2E-16）。值得注意的是，3q29缺失对女性（OR = 41.8，p = 4.78E-05）的ASD风险影响大于男性（OR = 24.6，p = 6.06E-09）；这与我们的研究样本中男性人口比例从4：1减少到2：1一致。尽管71％的病例未报告ASD的诊断，但有证据表明存在严重的社会残疾（3q29Del SRS T评分= 71.8，对照SRS T评分= 45.9，p = 2.16E-13）。病例还报告说，与对照组相比，广泛性焦虑症的发生率有所增加（28.0％比6.2％，p = 0.001），在Achenbach诊断和统计手册导向的子量表上，平均得分的提高反映了这一点（p <0.001）。最后，案例显示，与特发性ASD相比，SRS上的ASD特征明显不同，受限制的兴趣和重复行为大大增加，但社交动机仅有轻度损害。结论我们的3q29Del样本可显着丰富ASD诊断，尤其是在女性中，即使未报告ASD诊断，自闭症的特征也可能存在。此外，该人群中的ASD特征星座与特发性ASD截然不同，其社会动机受到的损害较小。我们的研究表明，ASD评估应成为3q29Del个体的护理标准。从研究的角度来看，