Trimeche Omeyma, Sakka Rania, Hajji Ekram, Missaoui Abdelmouhaymen, Ben Amor Bilel, Bayar Ines, Abid Sana, Marmouch Hela, Sayedi Hanen, Khochtali Ines
Fattouma Bourguiba University Hospital of Monastir, Monastir, Tunisia
Histology and Cytogenetics, Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.
J Med Genet. 2025 Jan 27;62(2):109-116. doi: 10.1136/jmg-2024-110253.
Neurofibromatosis-Noonan syndrome (NFNS) is an extremely rare genetic entity combining the clinical phenotype of two conditions: neurofibromatosis type 1 syndrome (NF1) and Noonan syndrome (NS). Nevertheless, many inconsistencies reside in our understanding of this condition, mainly its clinical features and genetic background. Through this systematic review, we aim to shed light on the epidemiological features, the broad clinical spectrum, the underlying genetic defects and the associated comorbidities of NFNS.
Medline, Scopus and Google Scholar were searched for publications on the clinical and genetic features of patients with NFNS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and the study protocol was registered in PROSPERO.
Of 951 records screened, 42 were eligible. The mean age at diagnosis was 14.7 years ranging from 0 to 69 years. As for the circumstance of discovery of NFNS, it was dominated by family investigation followed by neurofibromas, facial dysmorphia and short stature (SS). Prematurity was noted in 40.9% of cases. The hallmark features of NFNS at diagnosis were 'café au lait' macules, typical facial dysmorphia of NS, postnatal SS, pectus abnormalities, broad neck and lentigines. Macrocephaly, scoliosis and cardiopathies occurred in 26%, 42.4% and 36.9% of cases, respectively. Tumours were found in 18.4% of cases. As for the genetic foundation of NFNS, gene mutations were depicted in 87.5% of individuals.
Based on our findings, we emphasise on the importance of searching for NS features in patients with NF1 since the prognosis, comorbidities and consequently management could be altered.
42024522238.
神经纤维瘤病-努南综合征（NFNS）是一种极为罕见的遗传疾病，它合并了两种疾病的临床表型：1型神经纤维瘤病综合征（NF1）和努南综合征（NS）。然而，我们对这种疾病的认识存在许多不一致之处，主要体现在其临床特征和遗传背景方面。通过本系统综述，我们旨在阐明NFNS的流行病学特征、广泛的临床谱、潜在的基因缺陷以及相关的合并症。
检索了Medline、Scopus和谷歌学术上关于NFNS患者临床和遗传特征的出版物。遵循系统评价和Meta分析的首选报告项目指南，并将研究方案注册到PROSPERO中。
在筛选的951条记录中，42条符合条件。诊断时的平均年龄为14.7岁，范围从0岁到69岁。至于NFNS的发现情况，以家族调查为主，其次是神经纤维瘤、面部畸形和身材矮小（SS）。40.9%的病例有早产情况。NFNS诊断时的标志性特征是“牛奶咖啡”斑、NS典型的面部畸形、出生后身材矮小、胸壁异常、宽颈和雀斑。大头畸形、脊柱侧弯和心脏病分别发生在26%、42.4%和36.9%的病例中。18.4%的病例发现有肿瘤。至于NFNS的遗传基础，87.5%的个体存在基因突变。
基于我们的研究结果，我们强调在NF1患者中寻找NS特征的重要性，因为这可能会改变预后、合并症以及后续的治疗管理。
PROSPERO注册号：42024522238。
