Clinical implications of mosaicism: a 10-year retrospective review of 83 families in a university-affiliated genetics clinic.

Mosaicism refers to the coexistence of two or more genetically distinct cell populations in an individual from a single fertilized egg. We performed a retrospective analysis of all patients diagnosed with mosaic disorders between 2010 and 2021 in a university-affiliated genetics clinic, which attends to territory-wide genetic consultations. All patients with confirmed mosaic diagnoses through reproductive (n = 6), prenatal (n = 24), and postnatal (n = 53) testing were examined. We observed that mosaic 45, X (n = 31) and PIK3CA-related overgrowth spectrum (n = 16) disorders were among the most prevalent diagnoses in the clinic, and the total percentage of patients with mosaicism in our cohort was 2.0% (83/4157). A review of the diagnostic journey highlights the challenge in diagnosing mosaic disorders, whereby 38% of the subjects required more than one test sample, and 52% of the cases required more than one orthogonal method of detection to reach the correct diagnosis. While detection of mosaicism is passive through routine clinical testing, for example karyotyping in reproductive and prenatal care, in postnatal care, clinicians can more actively drive the detection of mosaicism. Therefore, we recommend a low threshold for additional genetic testing in suspected mosaicism for more accurate diagnosis and counselling.