Yue Xinyu, Chen Meiping, Ke Xiaoan, Yang Hongbo, Gong Fengying, Wang Linjie, Duan Lian, Pan Hui, Zhu Huijuan
Key Laboratory of Endocrinology of National Health Commission, State Key Laboratory of Complex Severe and Rare Diseases, Department of Endocrinology, Peking Union Medical College, Chinese Academy of Medical Science, Peking Union Medical College Hospital, Beijing, China.
Clin Endocrinol (Oxf). 2025 Jul 1. doi: 10.1111/cen.15293.
Wiedemann-Steiner syndrome (WSS) due to KMT2A variant is a rare autosomal dominant genetic heterogeneity disorder associated with short stature, the exact genetic mechanism of which is still unknown. This study aims to define the clinical, therapeutic and molecular findings of three new WSS patients from unrelated families, and to summarize the clinical characteristics and response to recombinant human growth hormone (rhGH) therapy.
DESIGN, PATIENTS AND MEASUREMENTS: Three male patients with short stature were included, and whole-exome sequencing (WES) was performed. All reported patients with WSS worldwide caused by KMT2A variants were reviewed.
The average age of the three patients was 8.3 ± 8.9 years, with an average height Z-score of -3.9 ± 1.8. Three KMT2A variants were detected with the aid of WES. A total of 333 cases of WSS have been reported, with 269 types of KMT2A gene variants described. WSS was characterized by intellectual disorder (92.9%, 250/269), developmental delay (87.9%, 175/199), generalized hypertrichosis (76.7%, 66/86) and short stature (70.9%, 61/86). The height Z-score of 14 patients received rhGH treatment significantly increased from -3.3 ± 1.2 to -1.8 ± 1.0 (p < 0.001) after an average treatment duration of 25.7 ± 23.1 months, and was positively correlated with the duration of treatment (r = 0.899, p < 0.0001). There was no significant difference in the height Z-score change between seven growth hormone deficiency (GHD) patients and five non-GHD patients after rhGH treatment.
This study provided a comprehensive analysis between phenotypes and genotypes of KMT2A variants and WSS. Our findings indicated that patients with WSS may experience favourable outcomes with rhGH therapy.
由KMT2A变异导致的维德曼-施泰纳综合征（WSS）是一种罕见的常染色体显性遗传异质性疾病，与身材矮小有关，其确切的遗传机制尚不清楚。本研究旨在明确来自非亲缘家庭的3例新的WSS患者的临床、治疗及分子学发现，并总结其临床特征及对重组人生长激素（rhGH）治疗的反应。
设计、患者及测量方法：纳入3例身材矮小的男性患者，并进行全外显子测序（WES）。对全球范围内所有报道的由KMT2A变异导致的WSS患者进行回顾。
3例患者的平均年龄为8.3±8.9岁，平均身高Z值为-3.9±1.8。借助WES检测到3种KMT2A变异。共报道了333例WSS病例，描述了269种KMT2A基因变异类型。WSS的特征为智力障碍（92.9%，250/269）、发育迟缓（87.9%，175/199）、全身性多毛症（76.7%，66/86）和身材矮小（70.9%，61/86）。14例接受rhGH治疗的患者，平均治疗25.7±23.1个月后，身高Z值从-3.3±1.2显著增加至-1.8±1.0（p<0.001），且与治疗持续时间呈正相关（r=0.899，p<0.0001）。rhGH治疗后，7例生长激素缺乏（GHD）患者和5例非GHD患者的身高Z值变化无显著差异。
本研究对KMT2A变异与WSS的表型和基因型进行了全面分析。我们的研究结果表明，WSS患者接受rhGH治疗可能会有良好的疗效。
