Abstract：
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by pathogenic variants in FBN1, with a hitherto unknown association with cancer. Here, we present two females with MFS who developed pediatric neuroblastoma. Patient 1 presented with neonatal MFS and developed an adrenal neuroblastoma with unfavorable tumor genetics at 10 months of age. Whole genome sequencing revealed a germline de novo missense FBN1 variant (NP_000129.3:p.(Asp1322Asn)), resulting in intron 32 inclusion and exon 32 retention. Patient 2 was diagnosed with classic MFS, caused by a germline de novo frameshift variant in FBN1 (NP_000129.3:p.(Cys805Ter)). At 18 years, she developed high-risk neuroblastoma with a somatic ALK pathogenic variant (NP_004295.2:p.(Arg1275Gln)). We identified 32 reported cases of MFS with cancer in PubMed, yet none with neuroblastoma. Among patients, we observed an early cancer onset and high frequency of MFS complications. We also queried cancer databases for somatic FBN1 variants, finding 49 alterations reported in PeCan, and variants in 2% of patients in cBioPortal. In conclusion, we report the first two patients with MFS and neuroblastoma and highlight an early age at cancer diagnosis in reported patients with MFS. Further epidemiological and functional studies are needed to clarify the growing evidence linking MFS and cancer.
摘要：
马凡氏综合征（MFS）是由FBN1中的致病变异引起的常染色体显性结缔组织疾病，与癌症有迄今为止未知的关联。这里,我们介绍了两名患有MFS的女性，他们发展为小儿神经母细胞瘤。患者1出现新生儿MFS，并在10个月大时发展出具有不利肿瘤遗传学的肾上腺神经母细胞瘤。全基因组测序显示种系从头错义FBN1变体（NP_000129.3：p。（Asp1322Asn）），导致内含子32包含和外显子32保留。患者2被诊断为经典MFS，由FBN1中的种系从头移码变体引起（NP_000129.3：p。（Cys805Ter））。18岁时,她开发了具有体细胞ALK致病变体的高风险神经母细胞瘤（NP_004295.2：p。（Arg1275Gln）。我们在PubMed中确定了32例报告的MFS癌症病例，但没有神经母细胞瘤。在患者中，我们观察到早期癌症发作和高频率的MFS并发症。我们还查询了癌症数据库中的体细胞FBN1变异，在PeCan发现49个改动，以及cBioPortal中2%患者的变异。总之,我们报告了前2例MFS和神经母细胞瘤患者,并在报告的MFS患者中强调了癌症诊断的早期年龄.需要进一步的流行病学和功能研究来澄清越来越多的证据将MFS与癌症联系起来。
