Mehawej Cybel, Chouery Eliane, Al Hage Chehade Ghada, Bejaoui Yosra, Mahfoud Daniel, Gerges Maya, Delague Valérie, El Hajj Nady, Megarbane Andre
Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos, Lebanon.
Pediatric Endocrinology and Diabetology, Pediatrics Department, Hammoud Hospital University Medical Center, Saida, Lebanon.
Mol Syndromol. 2023 Jun;14(3):219-224. doi: 10.1159/000527215. Epub 2023 Jan 17.
Overgrowth syndromes are a heterogeneous group of genetic disorders characterized by excessive growth, often accompanied by additional clinical features, such as facial dysmorphism, hormonal imbalances, cognitive impairment, and increased risk for neoplasia. Moreno-Nishimura-Schmidt (M-N-S) overgrowth syndrome is a very rare overgrowth syndrome characterized by severe pre- and postnatal overgrowth, dysmorphic facial features, kyphoscoliosis, large hands and feet, inguinal hernia, and distinctive skeletal features. The clinical and radiological features of the disorder have been well delineated, yet its molecular pathogenesis remains unclear.
We report on a Lebanese boy with M-N-S syndrome, whose clinical manifestations were compared with those of previously reported 5 affected individuals. Whole-exome sequencing combined with comparative genome hybridization analysis failed to delineate the molecular basis of the phenotype. However, epigenetic studies revealed a different methylation status of several CpG sites between him and healthy controls, with methyltransferase activity showing the most significant enrichment.
An additional case of M-N-S syndrome recapitulated the clinical and radiological manifestations described in the previous reports. The data in the epigenetic studies implicated that abnormal methylations might play an essential role in development of the disease phenotype. However, additional studies in a clinically homogeneous cohort of patients are crucial to confirm this hypothesis.
过度生长综合征是一组异质性遗传疾病，其特征为过度生长，常伴有其他临床特征，如面部畸形、激素失衡、认知障碍以及肿瘤发生风险增加。莫雷诺 - 西村 - 施密特（M - N - S）过度生长综合征是一种非常罕见的过度生长综合征，其特征为严重的产前和产后过度生长、面部畸形特征、脊柱侧凸、手足增大、腹股沟疝以及独特的骨骼特征。该疾病的临床和放射学特征已得到明确描述，但其分子发病机制仍不清楚。
我们报告了一名患有M - N - S综合征的黎巴嫩男孩，并将其临床表现与之前报道的5名受累个体进行了比较。全外显子测序结合比较基因组杂交分析未能确定该表型的分子基础。然而，表观遗传学研究发现他与健康对照之间几个CpG位点的甲基化状态不同，其中甲基转移酶活性表现出最显著的富集。
另一例M - N - S综合征重现了先前报道中描述的临床和放射学表现。表观遗传学研究数据表明，异常甲基化可能在疾病表型的发展中起重要作用。然而，在临床特征均一的患者队列中进行更多研究对于证实这一假设至关重要。
