Disorders of sexual differentiation: I. Genetics and pathology

Abstract

Objectives: To provide a summary of the recent major advances in the field of molecular genetics and understanding of psychosexual development, as these developments have resulted in changes in terminology and classification of disorders of sexual differentiation (DSD)/intersex; and to provide a quick and simplified review of the basic information.

Methods: Recent publications (over the last 10 years) were identified by a PubMed search, as were relevant previous studies, using the keywords; 'sex chromosomes', 'psychosexual development', 'classifications', 'disorders of sexual differentiation', 'Chicago consensus', 'gonadal malignancy', 'intersex' and 'ambiguous genitalia'.

Results: The newly proposed terminology and classification has eliminated some confusion for both patient and family, as well as among health professionals. The new advances have facilitated the categorisation of gonadal malignancy in patients with DSD into high-, intermediate- and low-risk groups.

Conclusions: The major changes in terminology and classification of DSD should be considered as the first steps on a long road of research effort. The current available data remain far from sufficient. More molecular genetics studies will allow a better understanding of the causes of each condition of DSD.

Keywords: CAH, congenital adrenal hyperplasia; CAIS, complete androgen insensitivity syndrome; CIS, carcinoma in situ; Chicago Consensus; Classification; DSD, disorder(s) of sexual differentiation; Gonadal malignancy; Intersex; MGD, mixed gonadal dysgenesis; MIS, Müllerian-inhibiting substance; PMDS, persistent Müllerian duct syndrome; Psychosexual development; SF-1, steroidogenic factor 1; SRY, sex-determining region on the Y chromosome; Sex chromosomes; WT-1, Wilms’ tumour-1 gene; hCG, human chorionic gonadotrophin.

Figure 1

Ovotesticular DSD: Note the tendency to a male phenotype with hypospadias.

Figure 2

MGD (a) Note the right testis is fully descended in the scrotum; the left streak gonad is in the inguinal canal, and hypospadias and (b) the streak gonad is associated with the Fallopian tube and the epididymis.

Figure 3

(a) A patient with CAH Prader 4 and (b) a patient with CAH Prader 2.

Figure 4

(a) A patient with CAIS. Note a normal, tall and hairless female with normal breast development and scanty pubic hair and (b) note the feminine external genitalia, a very short and shallow utricle and two testicles in the labia.