Long-term survival without high cancer risk in a cohort of 24 patients with Apert syndrome

Journal article

The classification of congenital malformations has been transformed over recent decades by advances in genetic analysis, so that the natural history of many disorders during childhood is well described. However, implications for adult prognosis and survival are often poorly documented. In Apert syndrome, caused by heterozygous germline mutations in the fibroblast growth factor receptor type 2 gene (FGFR2), the question of prognosis is particularly pertinent because FGFR2 is a known cancer driver gene (oncogene) and the identical mutations, when arising somatically, are enriched in specific tumours, notably endometrial carcinoma. We exploited a unique resource provided by a series of 24 UK patients described by Dr Eric Blank in 1960, and used tracing of cancer events and deaths through the National Health Service Central Register to determine the long-term outcome of these individuals until 2013, a period spanning 53 years. Twelve individuals (50%) were still alive and without any cancer registration, at the end of the study; of the remainder, two could not be traced and ten were known to have died, with four deaths related to malignancies. We conclude that Apert syndrome is not, in many affected individuals, associated either with substantial shortening of lifespan, or with a high risk of developing particular types of cancer. Explanation of the lack of strong cancer predisposition, despite the oncogenic nature of the FGFR2 mutations, may lie in the different signalling relationship that a mutant cell has with its neighbours when the mutation is present constitutionally, compared to occurrence as a somatic change.

Authors: Cairns, BJ; Davidson, DM; Smithson, SF; Wilkie, AOM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: European Journal of Human Genetics
• Publication date: 2026-05-04
• Acceptance date: 2026-04-21
• DOI: 10.1038/s41431-026-02122-w
• EISSN: 1476-5438
• ISSN: 1018-4813
• Language: English
• Keywords: Apert syndrome; Fibroblast growth factor receptor 2; Mutation; Endometrial cancer; Somatic cell; Cancer; Germline; Cohort; Germline mutation