Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.
Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Am J Med Genet A. 2024 Jun;194(6):e63540. doi: 10.1002/ajmg.a.63540. Epub 2024 Jan 19.
Coffin-Siris Syndrome (CSS, MIM 135900) is now a well-described genetic condition caused by pathogenic variants in the Bromocriptine activating factor (BAF) complex, including ARID1B, ARID1A, ARID2, SMARCA4, SMARCE1, SMARCB1, SOX11, SMARCC2, DPF2, and more recently, BICRA. Individuals with CSS have a spectrum of various medical challenges, most often evident at birth, including feeding difficulties, hypotonia, organ-system anomalies, and learning and developmental differences. The classic finding of fifth digit hypo- or aplasia is seen variably. ARID2, previously described, is one of the less frequently observed gene changes in CSS. Although individuals with ARID2 have been reported to have classic features of CSS including hypertrichosis, coarse facial features, short stature, and fifth digit anomalies, as with many of the other CSS genes, there appears to be a spectrum of phenotypes. We report here a cohort of 17 individuals with ARID2 variants from the Coffin-Siris/BAF clinical registry and detail their medical challenges as well as developmental progress. Feeding difficulties, hypotonia, and short stature occur often, and hip dysplasia appears to occur more often than with other genes, however more severe medical challenges such as significant brain and cardiac malformations are rarer. Individuals appear to have mild to moderate intellectual impairment and may carry additional diagnoses such as ADHD. Further phenotypic description of this gene will aid clinicians caring for individuals with this rarer form of CSS.
Coffin-Siris 综合征(CSS,MIM 135900)是一种已被充分描述的遗传疾病,由 Bromocriptine 激活因子(BAF)复合物的致病性变异引起,包括 ARID1B、ARID1A、ARID2、SMARCA4、SMARCE1、SMARCB1、SOX11、SMARCC2、DPF2 等,最近还包括 BICRA。CSS 患者存在各种医疗挑战,大多数在出生时就很明显,包括喂养困难、低张力、器官系统异常以及学习和发育差异。第五指发育不全或缺失是 CSS 的经典表现之一,但表现形式存在差异。先前描述过的 ARID2 是 CSS 中较少观察到的基因变化之一。尽管携带 ARID2 变异的个体表现出 CSS 的经典特征,包括多毛症、粗糙面容、身材矮小和第五指异常,但与许多其他 CSS 基因一样,其表型似乎存在一定的范围。我们在此报告了来自 Coffin-Siris/BAF 临床登记处的 17 名携带 ARID2 变异的个体,并详细描述了他们的医疗挑战和发育进展。喂养困难、低张力和身材矮小经常发生,髋关节发育不良似乎比其他基因更常见,但更严重的医疗挑战如严重的大脑和心脏畸形则较为罕见。个体似乎存在轻度至中度智力障碍,可能还伴有其他诊断,如注意力缺陷多动障碍。进一步描述该基因的表型将有助于照顾这种罕见 CSS 形式的患者的临床医生。
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