马凡综合征 (MFS) 是一种由 FBN1 致病性变异引起的常染色体显性结缔组织疾病，与癌症的关系迄今未知。在这里，我们介绍了两名患有 MFS 的女性，她们患有小儿神经母细胞瘤。患者 1 患有新生儿 MFS，并在 10 个月大时患上肾上腺神经母细胞瘤，肿瘤遗传学不利。全基因组测序揭示了种系从头错义 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 被诊断为典型的 MFS，由 FBN1 种系从头移码变异 (NP_000129.3:p.(Cys805Ter)) 引起。 18 岁时，她患上了具有体细胞 ALK 致病性变异 (NP_004295.2:p.(Arg1275Gln)) 的高危神经母细胞瘤。我们在 PubMed 中发现了 32 例报告的患有癌症的 MFS 病例，但没有一例患有神经母细胞瘤。在患者中，我们观察到癌症发病较早且 MFS 并发症发生率较高。我们还查询了癌症数据库中的体细胞 FBN1 变异，发现 PeCan 中报告了 49 种变异，cBioPortal 中 2% 的患者存在变异。总之，我们报告了前两名患有 MFS 和神经母细胞瘤的患者，并强调了报告的 MFS 患者的癌症诊断年龄较早。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。© 2024 作者。 《美国医学遗传学杂志》A 部分由 Wiley periodicals LLC 出版。

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.© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.