Lob Karen, Sawka Danielle M, Gaitanis John N, Liu Judy S, Nie Duyu A
The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Pediatrics, Children's Hospital of Philadelphia , Philadelphia, USA.
J Autism Dev Disord. 2024 Aug 13. doi: 10.1007/s10803-024-06512-1.
We compared the epilepsy phenotypes in children with genetically defined versus undefined autism spectrum disorder (ASD). A single-center retrospective study was conducted to investigate diagnostic yields of different genetic testing for children with ASD. Patients with at least one testing modality were included and classified as having genetically defined ASD or not based on updated genotype-phenotype correlation. Of the 523 patients included, 79 (15.1%) had results explaining their ASD diagnosis. WES (whole exome sequencing) outperformed CMA (chromosomal microarray) on diagnostic yield (23.0% versus 8.3%). Compared to those with non-diagnostic test(s), children with genetically defined ASD were associated with higher rates for microcephaly, hypotonia, dysmorphic features, and developmental delay/regression. The prevalence of epilepsy was significantly higher in children with genetically defined ASD than those without a genetic diagnosis (35.4% versus 16.4%, p < 0.001, power = 0.97). Furthermore, children with genetically defined ASD had a younger age of epilepsy onset (median 2.2 versus 5.0 years, p = 0.002, power = 0.90) and a higher rate of drug-resistant epilepsy although not reaching statistical significance (35.7% versus 21.9%, p = 0.20). Our study has provided further evidence to support WES as first-tier test for children with ASD and that an early genetic diagnosis has the potential to inform further surveillance and management for ASD comorbid conditions including epilepsy.
我们比较了患有基因明确型与基因未明确型自闭症谱系障碍（ASD）儿童的癫痫表型。开展了一项单中心回顾性研究，以调查针对ASD儿童进行不同基因检测的诊断率。纳入至少接受过一种检测方式的患者，并根据最新的基因型-表型相关性将其分类为患有基因明确型ASD或非基因明确型ASD。在纳入的523例患者中，79例（15.1%）的检测结果解释了其ASD诊断。全外显子组测序（WES）在诊断率方面优于染色体微阵列分析（CMA）（23.0%对8.3%）。与检测结果未明确诊断的患者相比，基因明确型ASD儿童出现小头畸形、肌张力减退、畸形特征及发育迟缓/退化的比率更高。基因明确型ASD儿童的癫痫患病率显著高于无基因诊断的儿童（35.4%对16.4%，p<0.001，检验效能=0.97）。此外，基因明确型ASD儿童的癫痫发病年龄更小（中位年龄2.2岁对5.0岁，p=0.002，检验效能=0.90），尽管未达到统计学显著性，但耐药性癫痫的发生率更高（35.7%对21.9%，p=0.20）。我们的研究提供了进一步的证据，支持将WES作为ASD儿童的一线检测方法，并且早期基因诊断有可能为包括癫痫在内的ASD合并症的进一步监测和管理提供依据。
