KBG syndrome is characterized by dental, craniofacial and skeletal anomalies, short stature and global developmental delay or intellectual disability. It is caused by microdeletions or truncating mutations of ANKRD11. We report four unrelated probands with this syndrome due to de novo ANKRD11 aberrations that may contribute to a better understanding of the genetics and pathophysiology of this autosomal dominant syndrome. Clinical, cognitive and MRI assessments were performed. Three of the patients showed normal intellectual functioning, whereas the fourth had a borderline level of intellectual functioning. However, all of them showed deficits in various cognitive and socioemotional processes such as attention, executive functions, empathy or pragmatic language. Moreover, all probands displayed marked asymmetry of the uncinate fascicles and an abnormal gyrification pattern in the left frontal lobe. Thus, structural neuroimaging anomalies seem to have been overlooked in this syndrome. Disturbed frontal gyrification and/or lower structural integrity of the uncinate fascisulus might be unrecognized neuroimaging features of KBG syndrome caused by ANKRD11 aberrations. Present results also point out that this syndrome is not necessarily associated with global developmental delay and intellectual disability, but it can be related to other neurodevelopmental disorders or subclinical levels of attention-deficit hyperactivity disorder, autism, communication disorders or specific learning disabilities.

KBG 综合征的特征是牙齿、颅面和骨骼异常、身材矮小和整体发育迟缓或智力残疾。它是由ANKRD11的微缺失或截短突变引起的。我们报告了四名因新发 ANKRD11而患有此综合征的不相关先证者可能有助于更好地了解这种常染色体显性遗传综合征的遗传学和病理生理学的异常。进行了临床、认知和 MRI 评估。其中三名患者的智力功能正常，而第四名患者的智力功能处于临界水平。然而，他们所有人都在各种认知和社会情感过程中表现出缺陷，例如注意力、执行功能、同理心或语用语言。此外，所有先证者都表现出明显的钩束不对称和左额叶异常的回旋模式。因此，这种综合征似乎忽略了结构性神经影像学异常。受干扰的额叶回旋和/或钩束肌结构完整性降低可能是由 ANKRD11 畸变引起的 KBG 综合征的未被识别的神经影像学特征。目前的研究结果还指出，这种综合征不一定与整体发育迟缓和智力障碍有关，但它可能与其他神经发育障碍或注意力缺陷多动障碍、自闭症、沟通障碍或特定学习障碍的亚临床水平有关。