Identification of previously unrecognized FAP in children with Gardner fibroma

Abstract

Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present b-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A4T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for b-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.

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

“…FAP must be excluded in a child with fibromas suggestive of Gardner syndrome because de novo variants can occur in patients with a negative family history, as seen in this patient and other cases (Levesque et al 2010). However, diagnosis may also identify previously unrecognized FAP families (Vieira et al 2015), so genetic testing of parents and siblings is a critical part of the evaluation process.…”

From Gardner fibroma diagnosis to constitutional APC mutation detection: a one‐way street

“…In all the other patients, patients who presented a GAF plus a positive family history of FAP and constitutional APC mutations were identified. Later, Vieira et al., focused on the role of GAF as a sentinel of FAP. The authors described two infants with both GAF and a previously unrecognized familial history of FAP.…”

“…Given that GAF had recently been identified as a potential sentinel of familial adenomatous polyposis (FAP) , the molecular analysis of the APC gene on constitutional DNA was performed in our patient by Sanger sequencing and by multiple ligation‐dependent probe amplification (SALSA MLPA kit P043 APC, lot. C1‐1212).…”

Neonatal Gardner Fibroma Leads to Detection of Familial Adenomatous Polyposis: Two Case Reports

“…Viera et al reported two infants with GF which led to previously unrecognized FAP in the families. 11 In their patients, immunofluorescent staining of β-catenin in the tumor, which accumulates in cells with biallelic truncation of APC because of the impairment of APC-mediated degradation of βcatenin, 4 led to the strong suspicion of underlying FAP. This may well be a future diagnostic tool in evaluating the role of GF in detection of FAP.…”