By sequencing all genes (exome/genome sequencing) we might find disease-causing mutations also in genes unrelated to the phenotype in question, but which may cause severe health problems (e.g. mutations causing susceptibility to cancer or certain heart diseases). These are called incidental findings (or secondary findings). For example, we might find a breast cancer-predisposing mutation in a patient tested for thoracic aortic aneurysm (e.g. a BRCA1 mutation). In such a case, if the patient has previously given consent, the breast-cancer mutation will also be reported. Incidental findings are relatively infrequent, as they may be detected in just 1-3% patients. It should be reminded that an incidental finding may be of relevance also for patient’s blood relatives (e.g. parents and siblings), as they may carry the same genetic variant.
The American College of Medical Genetics has issued a list of genes for which incidental findings should be reported. As of 30.04.2015, this list includes the following genes:
Condition | Typical Age of Onset | Gene | Inheritance |
Hereditary breast and ovarian cancer | Adult | BRCA1BRCA2 | Autosomal dominant |
Li–Fraumeni syndrome | Child/adult | TP53 | Autosomal dominant |
Peutz–Jeghers syndrome | Child/adult | STK11 | Autosomal dominant |
Lynch syndrome | Adult | MLH1MSH2MSH6PMS2 | Autosomal dominant |
Familial adenomatous polyposis | Child/adult | APC | Autosomal dominant |
MYH-associated polyposis; adenomas, multiple colorectal, FAP type 2; colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas | Adult | MUTYH | Autosomal recessive |
Von Hippel–Lindau syndrome | Child/adult | VHL | Autosomal dominant |
Multiple endocrine neoplasia type 1 | Child/adult | MEN1 | Autosomal dominant |
Multiple endocrine neoplasia type 2 | Child/adult | RET | Autosomal dominant |
Familial medullary thyroid cancer | Child/adult | RET | Autosomal dominant |
PTEN hamartoma tumor syndrome | Child/adult | PTEN | Autosomal dominant |
Retinoblastoma | Child | RB1 | Autosomal dominant |
Hereditary paraganglioma– pheochromocytoma syndrome | Child/adult | SDHDSDHAF2SDHCSDHB | Autosomal dominant |
Tuberous sclerosis complex | Child | TSC1TSC2 | Autosomal dominant |
WT1-related Wilms tumor | Child | WT1 | Autosomal dominant |
Neurofibromatosis type 2 | Child/adult | NF2 | Autosomal dominant |
Ehlers–Danlos syndrome, vascular type 1 | Child/adult | COL3A1 | Autosomal dominant |
Marfan syndrome, Loeys–Dietz syndromes, and familial thoracic aortic aneurysms and dissections | Child/adult | FBN1TGFBR1TGFBR2SMAD3ACTA2MYLKMYH11 | Autosomal dominant |
Hypertrophic cardiomyopathy, dilated cardiomyopathy | Child/adult | MYBPC3MYH7TNNT2TNNI3TPM1MYL3ACTC1PRKAG2GLAMYL2LMNA | Autosomal dominant / X-linked |
Catecholaminergic polymorphic ventricular tachycardia | RYR2 | Autosomal dominant | |
Arrhythmogenic right-ventricular cardiomyopathy | Child/adult | PKP2DSPDSC2TMEM43DSG2 | Autosomal dominant |
Romano–Ward long QT syndrome types 1, 2, and 3, Brugada syndrome | Child/adult | KCNQ1KCNH2SCN5A | Autosomal dominant |
Familial hypercholesterolemia | Child/adult | LDLRAPOBPCSK9 | Autosomal dominant / Semidominant |
Malignant hyperthermia susceptibility | Child/adult | RYR1CACNA1S | Autosomal dominant |
