KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.

中文翻译：

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KBG综合征的新型突变和未报告的临床特征。

KBG综合征是由ANKRD11内的致病变异或包括ANKRD11在内的16q24.3缺失引起的常染色体显性遗传疾病。它的特征是独特的面部特征，发育迟缓，身材矮小和骨骼异常。我们报告了12例不相关的患者，其中有针对性的分析怀疑并诊断为KBG。9名患者在ANKRD11中显示出点突变（先前没有报道），其中3名携带16q24.3缺失。所有患者均表现出典型的面部特征和巨大牙齿。骨骼异常是恒定的，大多数患者表现出关节僵硬。三名患者需要生长激素治疗，并且身高速度显着增加。在8例患者中发现了脑畸形。所有患者均表现出行为异常，大多数患者发育迟缓。2例患者血液学异常。我们强调，由于临床表型分析，ANKRD11的遗传分析可以轻松达到高于50％的检测率，尽管已知ANKRD11突变的患者子集显示出非常温和的特征，并且通过实施基因组更容易识别或外显子组测序。先前曾报道过少数患者关节僵硬，但这似乎是一个共同特征，对诊断很有帮助。可能会出现血液学异常，需要进行特定的随访。尽管已知有一部分ANKRD11突变的患者表现出非常温和的特征，并且可以通过实施基因组或外显子组测序更轻松地进行鉴定。先前曾报道过少数患者关节僵硬，但这似乎是一个共同特征，对诊断很有帮助。可能会出现血液学异常，需要进行特定的随访。尽管已知有一部分ANKRD11突变的患者表现出非常温和的特征，并且可以通过实施基因组或外显子组测序更轻松地进行鉴定。先前曾报道过少数患者关节僵硬，但这似乎是一个共同特征，对诊断很有帮助。可能会出现血液学异常，需要进行特定的随访。