Intersex genetic anomalies with malignant potential

Abstract

Purpose of review: Mutations in genes contributing to sexual determination and differentiation can cause clinical syndromes with potential for the development of malignant tumors. This article focuses on intersex disorders requiring surveillance for and/or operation to prevent or treat malignancies.

Recent findings: Classification of intersex disorders into risk groups gives guidance to physicians about children who are vulnerable to malignant degeneration of the gonads or kidneys. The gonads most at risk are both dysgenetic and intra-abdominal, and early gonadectomies are recommended as malignancies have been reported in infancy. Predominant risk groups include syndromes of gonadal dysgenesis and Ullrich-Turner syndrome. Partial gonadectomy is feasible in true hermaphrodites commensurate with sex of rearing. Histologically normal intra-abdominal gonads may be left through puberty (androgen insensitivity syndromes). A palpably normal descended gonad in a child with a Y chromosome can be observed if the child is reared as male. Certain intersex syndromes with splice variants of the WT1 gene are susceptible to Wilms' tumors (Frasier and Denys-Drash syndromes).

Summary: Prevention or early recognition of malignancy in intersex disorders requires knowledge of the risk factors including dysgenetic gonads, a Y chromosome with intra-abdominal gonads and dysgenetic syndromes with WT1 gene splice variants. This paper describes the evolution toward laparoscopic gonadectomy in intersex patients, as a means to remove abnormal gonads and associated ductal structures as dictated by the disease or syndrome.