Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals.

Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1478LeufsTer108). This boy presented a WDSTS phenotype associated with broad neurodevelopmental features, including an unusual speech difficulty (i.e., palilalia), and brain imaging studies revealed an array of cortical anomalies (e.g., frontal simplified gyration, focal frontal cortical dysplasia). These clinical and radiological observations expand the known WDSTS-related neurodevelopmental phenotypes and further strengthen the important role of KMT2A in brain function and cortical development.

Wiedemann-Steiner综合征（WDSTS）是一种罕见的遗传病，包括发育延迟/智力残疾（DD / ID），高发性立方形，身材矮小和独特的面部特征，这是由编码组蛋白甲基转移酶（H3K4）的KMT2A基因突变引起的调节染色质介导的转录。WDSTS光谱内已描述了不同的神经发育表型，包括某些受影响个体中的特殊自闭症谱系（ASD）亚型。

在这里，我们报道了通过下一代小组测序发现的9岁白人男性，携带一种新型的杂合性从头突变KMT2A移码变体（NM_001197104.2：c.4433delG; p。Arg1478LeufsTer108）。这个男孩表现出与广泛的神经发育特征相关的WDSTS表型，包括不寻常的言语困难（即骨），并且脑成像研究显示一系列皮质异常（例如额叶简化回旋，局灶性额叶皮质发育异常）。这些临床和放射学观察结果扩展了已知的WDSTS相关的神经发育表型，并进一步加强了KMT2A在脑功能和皮质发育中的重要作用。