DEFINITIONS AND EPIDEMIOLOGY
Disorders of sex developments (DSDs) are defined as conditions in which chromosomal, gonadal, and/or anatomical sex development are inconsistent.1,2 This definition is intentionally broader than previous definitions of intersex or ambiguous genitalia. As a result, only a subset of those with a DSD actually presents with ambiguous genitalia. The terms, hermaphrodite and pseudohermaphrodite, are considered to be inappropriate, derogatory, and are no longer used. The DSD classification schema includes several categories (46,XX DSD; 46,XY DSD, and gonadal/sex chromosome DSD) which can be useful for the initial approach to the diagnosis.
Since the term DSD was proposed, there have been intermittent criticisms due to the use of the word disorder as some feel that this term implies a defect and have suggested that a variation or difference be used in its place. However, realistically, most DSDs have manifestations that go beyond variations of normal external genital development. To consider all with genital ambiguity as having a variation of normal development is inappropriate and undermines the seriousness and untoward effects of having a DSD. For example, when a DSD is viewed as merely a normal variation, then it is implied that individuals with a DSD have no long-lasting consequences with pubertal development and/or fertility. The position for all those who care for patients with DSDs should be one that values each patient, irrespective of the type of DSD, with the overarching goal of fostering a good quality of life.
This revised DSD classification (Table 6-1) incorporates newer genetic information. The revised classification guides early diagnostic evaluation, through the use of phenotype and karyotype, to direct etiological evaluation and management. The diagnostic classification (Table 6-2) is imperfect because some conditions fail to fit into a single specific diagnostic category or fit into more than one category; for example, forms of gonadal dysgenesis may have a 46,XY, 46,XX, or 45,X/46,XY karyotype. Nevertheless, this schema includes the genetic cause when known and allows for definition of phenotypic variation within etiological categories. Although isolated mild hypospadias, that is, first-degree hypospadias, and idiopathic clitoromegaly are considered DSDs, they are generally characterized as anatomic variations.
Table 6-1.Nomenclature: Disorders of Sex Differentiation1 |Favorite Table|Download (.pdf) Table 6-1. Nomenclature: Disorders of Sex Differentiation1
|Sex Chromosome DSD ||46,XY DSD ||46,XX DSD |
|45,X Turner syndrome ||Aberrant testicular development ||Aberrant ovarian development |
|47,XXY Klinefelter syndrome ||Disorders of androgen synthesis or action ||Disorders of androgen excess |
|45,X/46,XY Mixed gonadal dysgenesis ||Disorders of MIH synthesis or action ||Vaginal or uterine atresia |
|46,XX/46,XY Chimeric, ovo-testicular ||Others: higher-order variations in Y chromosome; 47,XYY, 48,XXYY ||Others: higher-order variations in X chromosome; 47,XXX, 48,XXYY |
Table 6-2.Examples of Diagnoses Using DSD Classification1