Clinical management in mixed gonadal dysgenesis with chromosomal mosaicism: Considerations in newborns and adolescents

Abstract

Individuals born on the spectrum of genetic abnormalities known as mixed gonadal dysgenesis (MGD) have a wide range of anatomical findings and management can be challenging in the newborn and adolescent. Historically, many individuals with MGD have undergone gonadectomy to avert the risk of gonadal malignancy. However, gonadectomy deprives patients of the benefits of their endogenous hormones, potential fertility, and in the case with MGD, has historically been done prior to addressing gender identity. Some patient advocates have proposed a delayed approach to surgical reconstructions and/or gonadectomy in other differences/disorders of sex development (DSD), particularly in patients with congenital adrenal hyperplasia and androgen insensitivity syndrome. In many areas of the world, there continues to be a shift toward delayed reconstructions and hesitancy regarding irreversible gonadectomy. To date, no clinical management protocol addressing these issues from a patient-centered approach has been described. We review what is known about malignancy risk and propose a management protocol for those with MGD that involves shared decision making regarding the gonads and addresses the long-term challenges with regard to gender and anatomy.

Keywords: Chromosomal abnormality; Gonadectomy; Gonads; Malignancy risk; Mixed gonadal dysgenesis; Mosaicism.

Figure 1.. MGD Management Algorithm

This figure shows a treatment algorithm, modified from Cools et al, to assess malignancy risk and determine an individualized treatment plan for individuals diagnosed with 45,X/46,XY gonadal dysgenesis with mosaicism.