Anderson Kailyn, Cnota James, James Jeanne, Miller Erin M, Parrott Ashley, Pilipenko Valentina, Weaver Kathryn Nicole, Shikany Amy
Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Congenit Heart Dis. 2019 Mar;14(2):264-273. doi: 10.1111/chd.12721. Epub 2018 Dec 16.
To evaluate the prevalence of Noonan spectrum disorders (NSD) in a pediatric population with valvar pulmonary stenosis (vPS) and identify the clinical characteristics that differentiate those with NSD from those without NSD.
A retrospective chart review of 204 patients diagnosed with vPS between 9/1/2012 and 12/1/2016 at a pediatric medical center was performed. The quantitative features of vPS, genetic diagnosis information, and phenotypic characteristics of Noonan syndrome were collected. Chi-square test, Fisher's exact test, t test, Wilcoxon rank-sum test, and ANOVA were used for comparisons among the groups. Logistic regression was used to test for the association between the clinical characteristics and the presence of NSD.
Syndromic diagnoses were made in 10% of the children with vPS, with NSD accounting for 6%. Hypertrophic cardiomyopathy (P < .0001), short stature (P < .0001), developmental delay (P < .0001), ophthalmological abnormalities (P < .0001), pectus carinatum/excavatum (P = .01), neurological abnormalities (P = .022), and aortic stenosis (P = .031) were present more often in individuals with NSD compared to nonsyndromic vPS. A logistic regression analysis showed a 4.8-fold increase in odds for NSD for each additional characteristic (P < .0001).
At least 6% of the children with vPS have an underlying NSD. Individuals with vPS and NSD were significantly more likely to have additional features known to be associated with NSD than those with vPS without NSD. We conclude that vPS in the presence of one or more significant characteristics should prompt referral for genetic evaluation as a guide to ascertain patients at risk for NSD while optimizing the use of clinical genetics evaluation and potential genetic testing.
评估患有肺动脉瓣狭窄（vPS）的儿科人群中努南综合征谱系障碍（NSD）的患病率，并确定区分患有NSD和未患有NSD者的临床特征。
对2012年9月1日至2016年12月1日期间在一家儿科医疗中心被诊断为vPS的204例患者进行回顾性病历审查。收集了vPS的定量特征、基因诊断信息和努南综合征的表型特征。采用卡方检验、Fisher精确检验、t检验、Wilcoxon秩和检验和方差分析进行组间比较。使用逻辑回归检验临床特征与NSD存在之间的关联。
10%的vPS患儿被诊断为综合征，其中NSD占6%。与非综合征性vPS患者相比，NSD患者更常出现肥厚型心肌病（P <.0001）、身材矮小（P <.0001）、发育迟缓（P <.0001）、眼科异常（P <.0001）、鸡胸/漏斗胸（P =.01）、神经异常（P =.022）和主动脉狭窄（P =.031）。逻辑回归分析显示，每增加一个特征，NSD的患病几率增加4.8倍（P <.0001）。
至少6%的vPS患儿存在潜在的NSD。与没有NSD的vPS患者相比，患有vPS和NSD的个体更有可能具有已知与NSD相关的其他特征。我们得出结论，存在一个或多个显著特征的vPS应促使转诊进行基因评估，以指导确定有NSD风险的患者，同时优化临床遗传学评估和潜在基因检测的使用。
