Leslie Alison C, Ward Mitchell P, Dobyns William B
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.
Am J Med Genet A. 2024 Mar;194(3):e63416. doi: 10.1002/ajmg.a.63416. Epub 2023 Nov 7.
Schizophrenia (SCZ) is a well-studied neuropsychiatric condition that has been shown to have a high degree of genetic heritability. Still, little data on the specific genetic risk variants associated with the disease exists. Classification of the SCZ phenotype into SCZ-related endophenotypes is a promising methodology to parse out and elucidate the specific genetic risk variants for each. Here, we present a series of 17 previously reported individuals and a new proband with similar SCZ-related neuropsychiatric characteristics and shared brain imaging findings. Unsurprisingly, these individuals shared classic psychiatric features of SCZ. Interestingly, we also identified shared neuropsychiatric features in this series of individuals that had not been highlighted previously. A consistently decreased IQ, memory impairment, sleep and speech disturbances, and attention deficits were commonly reported findings. The brain imaging findings among these individuals also consistently showed posterior vermis predominant cerebellar hypoplasia (CBLH-V). Most individuals' diagnoses were initially described as Dandy-Walker malformation; however, our independent review of imaging suggests a more consistent pattern of posterior vermis predominant cerebellar hypoplasia rather than true Dandy-Walker malformation. While the specific genetic risk variants for this endophenotype are yet to be described, the aim of this paper is to present the shared neuropsychiatric features and consistent, symmetrical brain image findings which suggest that this subset of individuals comprises an endophenotype of SCZ with a high genetic solve rate.
精神分裂症(SCZ)是一种经过充分研究的神经精神疾病,已被证明具有高度的遗传遗传性。然而,关于与该疾病相关的特定遗传风险变异的数据仍然很少。将SCZ表型分类为与SCZ相关的内表型是一种很有前景的方法,可用于剖析和阐明每种表型的特定遗传风险变异。在此,我们报告了17例先前报道的个体以及1例具有相似SCZ相关神经精神特征和共享脑成像结果的新先证者。不出所料,这些个体具有SCZ的典型精神症状。有趣的是,我们还在这一系列个体中发现了先前未被强调的共享神经精神特征。智商持续下降、记忆障碍、睡眠和言语障碍以及注意力缺陷是常见的发现。这些个体的脑成像结果也一致显示以小脑蚓部后叶为主的小脑发育不全(CBLH-V)。大多数个体最初的诊断被描述为Dandy-Walker畸形;然而,我们对成像的独立评估表明,更一致的模式是以小脑蚓部后叶为主的小脑发育不全,而不是真正的Dandy-Walker畸形。虽然这种内表型的特定遗传风险变异尚未被描述,但本文的目的是呈现共享的神经精神特征和一致、对称的脑图像结果,这表明这一亚组个体构成了具有高遗传解析率的SCZ内表型。