Gardner syndrome describes a variant phenotype of familial adenomatous polyposis (FAP), primarily characterized by extracolonic lesions including osteomas, dental abnormalities, epidermal cysts, and soft tissue tumors. We describe a 2-yr-old boy presenting with a 2-cm soft tissue mass of the forehead. Pathologic evaluation revealed a nuchal-type/ Gardner-associated fibroma. Sequencing of the APC gene revealed a pathologic variant c.4666dupA. Parental sequencing of both blood and buccal tissue supported the de novo occurrence of this pathologic variant. Further imaging revealed a number of additional lesions including a large lumbar paraspinal desmoid, a 1-cm palpable lesion posterior to the left knee, firm lesions on bilateral heels, and multiple subdermal lesions. Colonoscopy was negative. This case illustrates a genetic variant of Gardner syndrome resulting in an aggressive early childhood phenotype and highlights the need for an individualized approach to treatment.
|Original language||English (US)|
|Journal||Cold Spring Harbor Molecular Case Studies|
|State||Published - 2019|
Bibliographical noteFunding Information:
Interestingly, dysfunction of the Wnt-β catenin pathway and abnormalities of cilia development have been hypothesized to be the underlying mechanisms of pathogenic extra-intestinal manifestations in FAP patients (Gómez and Knoers 2009; Nelson and Näthke 2013). This connection is supported by the presence of symptoms similar to Gardner syndrome in cilia-related disorders, and by the fact that APC is critical for the degradation of β-catenin in the Wnt-signaling pathway. Therefore, this pathway-specific function of APC may create a new context for therapeutic options for patients with Gardner syndrome.
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