Shetty Nikita, Brown William D, Massingham Lauren, Rogg Jeffrey, Quintos Jose Bernardo
Department of Pediatrics, Rhode Island Hospital/Hasbro Children's, Brown University Health, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
Division of Pediatric Neurology, Rhode Island Hospital/Hasbro Children's, Brown University Health, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
JCEM Case Rep. 2025 Aug 29;3(10):luaf188. doi: 10.1210/jcemcr/luaf188. eCollection 2025 Oct.
Individuals with Noonan syndrome (NS) are predisposed to hematologic cancers, solid tumors, and low-grade gliomas. We report an 8-year-old girl originally referred at age 14 months for short stature, developmental delay, and failure to thrive who was subsequently found to have pathogenetic variants both in and Family history included a maternal half-sister with NS and a mother carrying the mutation. Familial single-gene testing showed a heterozygous pathogenic variant in (c.417G > C p.Glu139Asp) suggesting NS, prompting initiation of growth hormone (GH) treatment at 26 months. Due to associated language delays, gross motor delays, microcephaly, and seizures, exome sequencing (ES) was pursued. ES identified a heterozygous de novo pathogenic variant (c.763C > T p.Arg255Ter) in and led to the additional diagnosis of Rett syndrome (RTT). Seizure onset prompted neuroimaging, which demonstrated hydrocephalus due to aqueductal stenosis secondary to a tectal neoplasm. GH treatment was discontinued. The co-occurrence of NS and RTT is rare. ES enabled the additional diagnosis of RTT in our patient with NS, who presented with atypical features and developmental regression.
努南综合征（NS）患者易患血液系统癌症、实体瘤和低级别胶质瘤。我们报告了一名8岁女孩，她在14个月大时因身材矮小、发育迟缓及生长发育不良前来就诊，随后被发现 和 基因均存在致病变异。家族史包括一位患有NS的同父异母姐姐和一位携带 突变的母亲。家族单基因检测显示 基因存在杂合致病变异（c.417G > C，p.Glu139Asp），提示为NS，促使在26个月时开始生长激素（GH）治疗。由于存在语言发育迟缓、大运动发育迟缓、小头畸形和癫痫发作，遂进行外显子组测序（ES）。ES在 基因中鉴定出一个杂合的新生致病变异（c.763C > T，p.Arg255Ter），并导致额外诊断为雷特综合征（RTT）。癫痫发作促使进行神经影像学检查，结果显示由于顶盖肿瘤继发导水管狭窄导致脑积水。GH治疗中断。NS和RTT同时出现的情况很罕见。ES使得我们患有NS且表现出非典型特征和发育倒退的患者得以额外诊断出RTT。
