Clinical Genetics Program, Hospital Universitario de Bellvitge, Barcelona, Spain; Cardiovascular Genetics, Health in Code, A Coruña, Spain; Genetics Department, Universitat Autònoma de Barcelona, Barcelona, Spain.
Inherited Myocardial Diseases Unit, Hospital Universitario de Bellvitge, Barcelona, Spain.
Gene. 2020 Jul 1;746:144658. doi: 10.1016/j.gene.2020.144658. Epub 2020 Apr 10.
Neurofibromatosis 1 (NF1) is an autosomal dominant disorder characterized by café-au-lait spots, intertriginous freckling, and multiple neurofibromas. Classically, it has been described that hypertrophic cardiomyopathy (HCM) may be a cardiovascular manifestation of neurofibromatosis 1, although the relationship between these two entities has not been fully established. We report a large Spanish family carrying a pathogenic truncating variant in NF1 (p.Arg2258Ter) causing neurofibromatosis 1, and a pathogenic missense variant in MYH7 (p. Arg453Cys), causing hypertrophic cardiomyopathy independently. A complete penetrance was observed in both genetic diseases, reinforcing the notion of deleterious effects of both rare variants. According to our report, hypertrophic cardiomyopathy in patients with NF1 should not be considered as part of the clinical spectrum in all cases. A careful and comprehensive assessment, including family evaluation and genetic testing for HCM should be considered as part of the diagnostic work-up in individuals presenting with both phenotypes.
神经纤维瘤病 1 型（NF1）是一种常染色体显性遗传病，其特征为咖啡牛奶斑、皱褶部位雀斑样色素沉着和多发性神经纤维瘤。经典理论认为，肥厚型心肌病（HCM）可能是神经纤维瘤病 1 型的心血管表现，尽管这两种疾病之间的关系尚未完全确定。我们报告了一个携带 NF1 致病截断变异（p.Arg2258Ter）导致神经纤维瘤病 1 型，以及 MYH7 致病性错义变异（p.Arg453Cys）导致肥厚型心肌病的大型西班牙家族。这两种遗传疾病均表现出完全外显，这强化了这两种罕见变异具有有害影响的观点。根据我们的报告，NF1 患者的肥厚型心肌病不应被认为是所有病例临床谱的一部分。对于同时存在两种表型的个体，应考虑进行包括家族评估和 HCM 基因检测在内的全面评估，作为诊断工作的一部分。
