Identification of aggressive Gardner syndrome phenotype associated with a de novo APC variant, c.4666dup

Patrick Kiessling, Eric Dowling, Yajue Huang, Mai Lan Ho, Karthik Balakrishnan, Brenda J. Weigel, W. Edward Highsmith, Zhiyv Niu, Lisa A. Schimmenti

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5 Scopus citations


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 languageEnglish (US)
Article numbera003640
JournalCold Spring Harbor Molecular Case Studies
Issue number2
StatePublished - 2019

Bibliographical note

Funding 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.

Publisher Copyright:
© 2019 Kiessling et al. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.


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