Pediatrics

XY Gonadal Dysgenesis in a Phenotypic Female Identified by Direct-to-Consumer Genetic Testing

We report a 16-year-old phenotypic female with 46,XY complete gonadal dysgenesis and metastatic dysgerminoma, unexpectedly discovered through direct-to-consumer (DTC) commercial genetic testing. This case underscores the importance of timely interdisciplinary care, including psychosocial intervention and consideration of gonadectomy, to optimize outcomes for individuals with differences of sex development. Her unique presentation highlights the implications of DTC genetic testing in a new diagnostic era and informs general pediatricians as well as specialists of nongenetic services about the value, capabilities, and limitations of DTC testing.

Oopherectomy in a Child to Reduce Cancer Risk: Oncogenetic, Ethical, and Legal Considerations

In the following case, we will discuss the clinical, ethical, and legal intricacies associated with the management of a young child with a hereditary cancer predisposition syndrome. Patients with germline pathogenic variants in SMARCA4 are at an increased risk for development of small cell carcinoma of the ovary-hypercalcemic type, malignant rhabdoid tumors, and some lung cancers. This case highlights the complexity of a case wherein a mother is found to have this genetic syndrome, and further testing reveals her daughter to have the same pathogenic variant. Through this case, we explore the oncologic, genetic, legal, and ethical considerations at play when making an irreversible decision for a child that affects her current and future medical and reproductive capacities. To do so would mitigate the risk of future malignancy, adding a layer of legal and ethical complexity. Although each contributor individually concludes that surgery in this case should be delayed, this case demonstrates the need for an individualized approach that considers medical evidence, patient and family interests, and child welfare.

Long-Term Adaptation Among Adolescent and Young Adult Children to Familial Cancer Risk

BACKGROUND It is important to examine adolescent and young adult (AYA) children’s long-term psychosocial and behavioral adaptation to disclosure of maternal BRCA-positive carrier status (BRCA+) to inform approaches for familial cancer risk communication, education, and counseling. METHODS Mothers underwent BRCA genetic testing 1 to 5 years earlier. Group differences in AYAs' self-reported outcomes were analyzed by maternal health and carrier status, and child age and sex. RESULTS A total of N = 272 AYAs were enrolled: 76.1% of their mothers were breast or ovarian cancer survivors and 17.3% were BRCA+. AYAs’ cancer risk behavior (tobacco and alcohol use, physical activity) and psychologic distress levels did not vary by maternal status. In bivariate analyses, AYAs of cancer-surviving mothers believed themselves to be at greater risk for, and were more knowledgeable about, cancer than AYAs of mothers without cancer. AYAs of BRCA+ mothers were more concerned about cancer, held stronger beliefs about genetic risk, and placed a higher value on learning about genetics. In adjusted models, maternal cancer history (not BRCA+) remained associated with AYAs’ greater perceptions of cancer risk (P = .002), and knowledge about cancer (P = .03) and its causes (P = .002). CONCLUSIONS Disclosing maternal BRCA+ status did not influence children’s lifestyle behavior or adversely affect quality of life long term. AYAs of BRCA+ mothers were more aware of and interested in genetic risk information. Such families may benefit from support to promote open communication about genetic testing choices.