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Abstract：
Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH). Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis. Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age. Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.
摘要：
目的：Wiedemann-Steiner综合征（WSS）是由KMT2A基因的有害杂合变体引起的一种罕见的常染色体显性疾病。本研究旨在描述中国WSS患者的表型和基因型特征，并评估重组人生长激素（rhGH）的治疗效果。方法：11名中国WSS儿童纳入我们的队列。他们的临床，成像,对生化和分子检查结果进行回顾性分析.此外，我们回顾了以前报道的41例中国WSS患者的表型特征,并将其纳入我们的分析.结果：在我们的队列中，11例WSS患者表现为经典临床表现，但是频率不同.最常见的临床特征是身材矮小（90.9%）和发育迟缓（90.9%），其次是智力残疾(72.7%)。最常见的影像学特征是心血管系统动脉导管未闭（57.1%）和卵圆孔未闭（42.9%），和大脑中的call体异常（50.0％）。在包括52名中国WSS患者的集合中，最常见的临床表现和影像学表现为发育迟缓(84.6%),智力残疾(84.6%)，身材矮小（80.8%）和延迟骨龄（68.0%），分别。11种不同的变体,包括三个已知的和八个新颖的变体，在我们的11例没有热点变异的WSS患者中发现了KMT2A基因。两名患者接受了rhGH治疗，并获得了令人满意的身高增长，但是一个发展了骨龄的加速。结论：我们的研究增加了11例新的WSS患者，揭示了中国WSS患者的不同临床特征，并扩展了KMT2A基因的突变谱。我们的研究还分享了rhGH在两名没有GH缺乏的WSS患者中的治疗效果。
