Krutish Angela, Kukurudz-Gorowski Rebekah, Borlot Felippe, Frosk Patrick, Rockman-Greenberg Cheryl, Mhanni Aizeddin A
Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
Front Genet. 2025 May 19;16:1595298. doi: 10.3389/fgene.2025.1595298. eCollection 2025.
Chromosome 16p13.3 deletions cause a contiguous gene deletion syndrome, ATR-16 syndrome. The classic phenotype of ATR-16 syndrome includes either alpha-thalassemia trait or hemoglobin H disease and intellectual disability; however, considerable variable expressivity has been reported with some patients having only an alpha-thalassemia disorder and others exhibiting a more severe phenotype with additional features.
We describe an adult male with ATR-16 syndrome (due to an unbalanced translocation involving chromosomes 11p15.5 and 16p13.3) who developed cognitive decline and increasing dyskinetic movements in his late twenties. Biochemical investigations and exome sequencing did not elucidate an alternative explanation for this decline. Furthermore, neither the deletion on chromosome 16 nor the duplication on chromosome 11 encompassed genes that could explain the decline.
While cognitive decline has not been previously reported in ATR-16 syndrome, this may be another feature of the condition that is subject to variable expressivity. Taking this together with the apparent increased prevalence of dementia in other neurodevelopmental conditions, we hypothesize that individuals with ATR-16 syndrome may be predisposed to early cognitive decline.
16号染色体p13.3缺失会导致一种连续性基因缺失综合征，即ATR-16综合征。ATR-16综合征的典型表型包括α地中海贫血特征或血红蛋白H病以及智力残疾；然而，据报道存在相当大的表型变异性，一些患者仅患有α地中海贫血症，而另一些患者则表现出更严重的表型及其他特征。
我们描述了一名患有ATR-16综合征（由于涉及11号染色体p15.5和16号染色体p13.3的不平衡易位）的成年男性，他在二十多岁后期出现认知能力下降和运动障碍加重。生化检查和外显子组测序未能阐明这种下降的其他原因。此外，16号染色体上的缺失和11号染色体上的重复均未包含可解释这种下降的基因。
虽然此前未在ATR-16综合征中报道过认知能力下降，但这可能是该病症具有表型变异性的另一个特征。结合其他神经发育病症中痴呆症明显增加的患病率，我们推测患有ATR-16综合征的个体可能易患早期认知能力下降。
