Yuan Meng, Shan Yuanyuan, Xu Fanshu, Yang Lin, Sun Chengjun, Cheng Ruoqian, Wu Bingbing, Zhang Zhehuan, Cao Yun, Zhang Rong, Zhou Wenhao, Cheng Guoqiang, Hu Liyuan
Department of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Endocrinology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Transl Pediatr. 2023 Jan 31;12(1):86-96. doi: 10.21037/tp-22-220. Epub 2023 Jan 10.
Shashi-Pena syndrome (SHAPNS) is a developmental disorder caused by mutations in additional sex combs-like Protein 2 (). Since 2016, only 12 cases from 10 families have been reported. However, neonatal period characteristics remain largely unknown. Herein, we report a case with a pathogenic variant in ASXL2 in a newborn.
A newborn was diagnosed with a previously unreported truncating mutation in ASXL2 (NM_018263.6) at 21 days and the clinical characteristics of all probands with ASXL2-related SHAPNS was reported in the literature. He had persistent hypoglycemia caused by inappropriate insulin levels and achieved stable glucose levels after octreotide treatment. Magnetic resonance imaging (MRI) revealed a small cerebellum, and fundoscopy showed bilateral retinal paving-stone-like white lesions. The results of trio-based whole exome sequencing (WES) were returned on the 21st day of life, and a heterozygous de novo truncating pathogenic c.1792C>T (p.Gln598*) variant in exon 11 of the gene was identified. The clinical features of our patient and another 10 probands with -related SHAPNS reported in the literature were included in this review. More than half shared recognizable clinical features, including hypertelorism (11/11), broad nasal tip (10/11), arched eyebrows (9/11), a large V-shaped glabellar nevus flammeus on the forehead (9/11), low-set ears (8/11), posteriorly rotated ears (7/11), proptosis (6/11) and deep palm creases (6/11). Major clinical issues included feeding difficulties (10/11), developmental delay (10/11), skeletal and/or extremity abnormalities (8/11), progressive macrocephaly (8/11), hypotonia (8/11), hypoglycemia (6/11) and seizures (6/11). Neurodevelopmental regression was possible in patients (2/11) with normal MRI findings who later developed nonfebrile seizures.
We present a newborn diagnosing the SHAPNS by trio-WES, which is the earliest age of diagnosis. The application of octreotide for hypoglycemia, the small cerebellum and bilateral paving-stone-like white lesions of the retinas are described for the first time in an individual with -related SHAPNS. Additional clinical reports of neonates with damaging ASXL2 variants are necessary to verify the mechanism and optimal treatment of ASXL2-related hypoglycemia, neurological damage and optic impairment. Neurological, endocrinological, ophthalmological, and rehabilitative follow-ups of these patients are necessary and important.
沙希 - 佩纳综合征（SHAPNS）是一种由额外性梳样蛋白2（ASXL2）突变引起的发育障碍。自2016年以来，仅报道了来自10个家庭的12例病例。然而，新生儿期特征在很大程度上仍不清楚。在此，我们报告一例新生儿ASXL2基因存在致病变异的病例。
一名新生儿在21天时被诊断出ASXL2（NM_018263.6）存在先前未报道的截短突变，并报道了文献中所有与ASXL2相关的沙希 - 佩纳综合征先证者的临床特征。他因胰岛素水平异常导致持续性低血糖，在奥曲肽治疗后血糖水平稳定。磁共振成像（MRI）显示小脑较小，眼底检查显示双侧视网膜铺路石样白色病变。基于三联体的全外显子组测序（WES）结果在出生后第21天返回，在该基因第11外显子中鉴定出一个杂合的新发截短致病变异c.1792C>T（p.Gln598*）。本综述纳入了我们患者以及文献中报道的另外10例与ASXL2相关的沙希 - 佩纳综合征先证者的临床特征。超过一半的患者具有可识别的临床特征，包括眼距增宽（11/11）、鼻尖宽大（10/11）、眉弓高拱（9/11）、前额有大的V形火焰状眉间痣（9/11）、耳位低（8/11）、耳向后旋转（7/11）、眼球突出（6/11）和手掌深纹（6/11）。主要临床问题包括喂养困难（10/11）、发育迟缓（10/11）、骨骼和/或肢体异常（8/11）、进行性巨头症（8/11）、肌张力低下（8/11）、低血糖（6/11）和癫痫发作（6/11）。MRI检查结果正常但后来出现无热惊厥的患者（2/11）可能发生神经发育倒退。
我们报告了一例通过三联体全外显子组测序诊断沙希 - 佩纳综合征的新生儿，这是最早的诊断年龄。首次描述了奥曲肽用于治疗低血糖，以及在一名与ASXL2相关的沙希 - 佩纳综合征患者中小脑较小和双侧视网膜铺路石样白色病变。需要更多新生儿ASXL2致病变异的临床报告来验证与ASXL2相关的低血糖、神经损伤和视力损害的机制及最佳治疗方法。对这些患者进行神经、内分泌、眼科和康复随访是必要且重要的。
