Williams-Beuren syndrome (WBS) is a multisystem disorder caused by a hemizygous deletion on 7q11.23 encompassing 26-28 genes. An estimated 2-5% of patients have "atypical" deletions, which extend in the centromeric and/or telomeric direction from the WBS critical region. To elucidate clinical differentiators among these deletion types, we evaluated 10 individuals with atypical deletions in our cohort and 17 individuals with similarly classified deletions previously described in the literature. Larger deletions in either direction often led to more severe developmental delays, while deletions containing MAGI2 were associated with infantile spasms and seizures in patients. In addition, head size was notably smaller in those with centromeric deletions including AUTS2. Because children with atypical deletions were noted to be less socially engaged, we additionally sought to determine how atypical deletions relate to social phenotypes. Using the Social Responsiveness Scale-2, raters scored individuals with atypical deletions as having different social characteristics to those with typical WBS deletions (p = .001), with higher (more impaired) scores for social motivation (p = .005) in the atypical deletion group. In recognizing these distinctions, physicians can better identify patients, including those who may already carry a clinical or FISH WBS diagnosis, who may benefit from additional molecular evaluation, screening, and therapy. In addition to the clinical findings, we note mild endocrine findings distinct from those typically seen in WBS in several patients with telomeric deletions that included POR. Further study in additional telomeric deletion cases will be needed to confirm this observation.

中文翻译：

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与威廉姆斯-伯伦综合征非典型缺失相关的社会、神经发育、内分泌和头部大小差异。

Williams-Beuren 综合征 (WBS) 是一种多系统疾病，由包含 26-28 个基因的 7q11.23 半合子缺失引起。估计有 2-5% 的患者有“非典型”缺失，从 WBS 关键区域向着丝粒和/或端粒方向延伸。为了阐明这些缺失类型之间的临床区别，我们评估了我们队列中 10 名具有非典型缺失的个体和 17 名具有文献中先前描述的类似分类缺失的个体。任一方向的较大缺失通常会导致更严重的发育迟缓，而含有 MAGI2 的缺失与患者的婴儿痉挛和癫痫发作有关。此外，包括 AUTS2 在内的着丝粒缺失的头部大小明显更小。由于注意到具有非典型缺失的儿童社交参与度较低，我们还试图确定非典型缺失与社会表型的关系。使用 Social Responsiveness Scale-2，评估者将具有非典型缺失的个体与具有典型 WBS 缺失的个体具有不同的社会特征（p = .001），在社会动机方面得分更高（更受损）（p = .005）非典型缺失组。认识到这些区别后，医生可以更好地识别患者，包括可能已经进行临床或 FISH WBS 诊断的患者，这些患者可能受益于额外的分子评估、筛查和治疗。除了临床发现外，我们还注意到在包括 POR 在内的一些端粒缺失患者中，与 WBS 中常见的内分泌发现不同。