Incidental finding of APC deletion in a child: double trouble or double chance? – a case report

Abstract

Background 22q11.2 deletion syndrome is one of the most common genomic disorders, characterized by the variable presence of facial dysmorphisms, congenital cardiac defects, velopharyngeal insufficiency/cleft palate, thymic hypoplasia/aplasia, immunodeficiency, parathyroid hypoplasia, developmental delay, learning disabilities, psychiatric disorders, renal, ocular, and skeletal malformations, hearing loss and laryngeal abnormalities. Chromosomal microarray (CMA) hybridization is one of the most performed diagnostic tests but as a genome wide analysis, it can point out relevant incidental copy number variations. Case presentation We report the case of a 2-year-old boy that came to our attention for mild psychomotor delay, poor growth, and minor facial anomalies. Considering a diagnosis of 22q11.2 deletion syndrome, we performed CMA that not only confirmed our diagnosis, but also pointed out an additional de novo 5q21.3q22.2 microdeletion, encompassing APC gene. As a result of the genetic testing we enrolled the patient in a tailored surveillance protocol that enabled the early detection of a hepatoblastoma. The child underwent surgical and chemotherapic treatments with complete cancer eradication. Conclusions The concurrent finding of an expected result and an additional deletion of APC gene represents an example of a relevant issue about the health and ethical management of secondary findings revealed by genome-wide tests. Furthermore, this report highlights the need to develop dedicated surveillance guidelines for children with APC-related polyposis and raise the question whether to suspect and screen for APC-related conditions in cases of sporadic hepatoblastomas.

Revisiting Secondary Information Related to Pharmacogenetic Testing

“…In pathology, and specifically with respect to whole genome sequencing (WGS) or exome genome sequencing (WES) (analogous to a whole body scan in radiology), secondary findings occur with the detection of genetic variants throughout the genome or exome that are unrelated to the clinical indication for testing (Amendola et al, 2015). Secondary findings have also been reported with other types of comprehensive genetic and genomic applications including noninvasive prenatal testing (Bianchi et al, 2015;Mastromoro et al, 2021) and chromosomal microarray testing (Rosina et al, 2021). Although much of the literature has focused on secondary findings in the germline, it is also possible to detect secondary findings present in somatic tissues in germline testing due to mixed cell populations in the patient specimen (Weitzel et al, 2018;Chao et al, 2021).…”

Hepatoblastoma in molecularly defined, congenital diseases

“…Various extraintestinal manifestations, such as neoplasms of soft and hard tissue or the central nervous system, have been associated with FAP (Groen et al, 2008). In addition, several case reports have confirmed that children with pathogenic germline APC variants have a significant risk of developing HB (Alkhouri et al, 2010;Augustyn & Wallerstein, 2009;Cetta et al, 1997;Evers et al, 2012;Rosina et al, 2021;Sanders & Furman, 2006;Thomas et al, 2003). The main clinical characteristics as well as the prognosis of individuals with HB and FAP does not seem to differ from those of patients with sporadic HB (Trobaugh-Lotrario et al, 2018).…”

Integrative evaluation and experimental validation of the immune-modulating potential of dysregulated extracellular matrix genes in high-grade serous ovarian cancer prognosis

“…However, it is currently unknown how the ECM environment of HGSOC differs from the normal ovarian environment and whether ECM modifications can offer diagnostic and therapeutic insights for this poor-prognosis cancer. Furthermore, it’s crucial to recognize that matrix components function not as isolated entities but as an interconnected network of matrix molecules [ 21 ]. Recent research has established the prognostic and predictive value of dysregulated stromal components in early non-small cell lung cancer [ 22 , 23 ].…”