Occurrence of cancer in Marfan syndrome: Report of two patients with neuroblastoma and review of the literature

• Published in: American journal of medical genetics. Part A Vol. 194; no. 12; pp. e63812 - n/a
• Main Authors: Maya‐González, Carolina, Delgado‐Vega, Angelica Maria, Taylan, Fulya, Lagerstedt Robinson, Kristina, Hansson, Lina, Pal, Niklas, Fagman, Henrik, Puls, Florian, Wessman, Sandra, Stenman, Jakob, Georgantzi, Kleopatra, Fransson, Susanne, Díaz De Ståhl, Teresita, Ek, Torben, Palmer, Ruth, Tesi, Bianca, Kogner, Per, Martinsson, Tommy, Nordgren, Ann
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2024; Wiley Subscription Services, Inc
• Subjects: Cancer; Cancer and Oncology; Cancer och onkologi; cancer predisposition; Connective tissue diseases; Epidemiology; FBN1; Hereditary diseases; Literature reviews; Marfan syndrome; Marfan syndrome (MFS); Medicin och hälsovetenskap; Neonates; Neuroblastoma; Patients; Pediatrics; Whole genome sequencing; neuroblastoma; cancer predisposition; Marfan syndrome (MFS); FBN1
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63812

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.