Abstract
Gardner syndrome is a neoplasic disease that associates intestinal polyposis and colorectal adenocarcinoma with osteomas and soft tissue tumors determined by germline mutations in the APC gene. The early diagnosis and identification of high-risk individuals are important because patients have a 100% risk of colon cancer. We present the case of a family with Gardner syndrome. Cephalometric, panoramic X-rays and CBCT of the proband and her brother showed multiple osteomas affecting the skull bones, mandible and paranasal sinuses. The detailed family history showed an autosomal dominant transmission with the presence of the disease in the mother and maternal grandfather of the proband. Both had the typical signs of disease and died in the fourth decade of life. Based on these aspects the clinical diagnosis was Gardner syndrome. By gene sequencing, a novel pathogenic variant c.4609dup (p.Thr1537Asnfs*7) in heterozygous status was identified in the APC gene in both siblings. We reviewed literature data concerning the correlation between the localization of mutations in the APC gene and the extracolonic manifestations of familial adenomatous polyposis as well as their importance in early diagnosis and adequate oncological survey of patients and families based on abnormal genomic variants.
Highlights
IntroductionColorectal cancer (CRC) is the third most common cancer worldwide (approximately 1.8 million new cancer diagnoses yearly) and the second most common cause of cancer death (over 880,000 deaths in 2018) [1]
Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death [1]
Siblings diagnosed with a new pathogenic variant in the APC regulator of WNT signaling pathway (APC) gene to highlight the importance of extracolonic manifestations and family history in the early diagnosis of familial adenomatous polyposis (FAP)
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide (approximately 1.8 million new cancer diagnoses yearly) and the second most common cause of cancer death (over 880,000 deaths in 2018) [1]. Exceptions are cases of hereditary syndromes predisposed to CRC (10% of all colorectal cancers), where, after the discovery of an index case, a large screening of the family follows [3,4]. Most early-onset cancers are monogenic (16–35% of total) [2,4,5,6,7]. The most common forms are Lynch Syndrome and familial adenomatous polyposis (FAP). The high percentage of monogenic cancers with early onset indicates and justifies genetic counselling and multigene panel testing [4]. Nearly half of patients with a genetic form of CRC do not have a positive family history [6]. Genetic diagnosis is important for patients, and for the identification and management of relatives at risk of inheriting the mutation
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