BRWD3 has been described as a cause of X-linked intellectual disability, but relatively little is known about the specific phenotype. We report the largest BRWD3 patient series to date, comprising 17 males with 12 distinct null variants and 2 partial gene deletions. All patients presented with intellectual disability, which was classified as moderate (65%) or mild (35%). Behavioral issues were present in 75% of patients, including aggressive behavior, attention deficit/hyperactivity and/or autistic spectrum disorders. Mean head circumference was +2.8 SD (2.8 standard deviations above the mean), and mean BMI was +2.0 SD (in the context of a mean height of +1.3 SD), indicating a predominant macrocephaly/obesity phenotype. Shared facial features included a tall chin, prognathism, broad forehead, and prominent supraorbital ridge. Additional features, reported in a minority (<30%) of patients included cryptorchidism, neonatal hypotonia, and small joint hypermobility. This study delineates the clinical features associated with BRWD3 null variants and partial gene deletions, and suggests that BRWD3 should be included in the differential diagnosis of patients with an overgrowth-intellectual disability (OGID) phenotype, particularly in male patients with a mild or moderate intellectual disability associated with macrocephaly and/or obesity.

中文翻译：

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BRWD3 中的空变体和缺失导致轻度中度智力障碍、大头畸形和肥胖的 X 连锁综合征：一系列 17 名患者。

BRWD3 已被描述为 X 连锁智力障碍的原因，但对特定表型知之甚少。我们报告了迄今为止最大的 BRWD3 患者系列，包括 17 名男性，有 12 个不同的无效变异和 2 个部分基因缺失。所有患者均出现智力障碍，分为中度（65%）或轻度（35%）。75% 的患者存在行为问题，包括攻击性行为、注意力缺陷/多动和/或自闭症谱系障碍。平均头围为 +2.8 SD（高于平均值 2.8 个标准差），平均 BMI 为 +2.0 SD（在平均身高为 +1.3 SD 的情况下），表明主要的大头畸形/肥胖表型。共同的面部特征包括高下巴、前突、宽前额和突出的眶上嵴。附加功能，据报道，少数（<30%）患者包括隐睾、新生儿肌张力减退和小关节过度活动。该研究描述了与 BRWD3 无效变异和部分基因缺失相关的临床特征，并建议 BRWD3 应包括在具有过度生长智力障碍 (OGID) 表型的患者的鉴别诊断中，特别是在具有轻度或中度智力的男性患者中与大头畸形和/或肥胖相关的残疾。