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Evaluation of the infant with atypical genitalia (disorder of sex development)

Christopher P Houk, MD
Lynne L Levitsky, MD
Section Editors
Laurence S Baskin, MD, FAAP
Mitchell Geffner, MD
Deputy Editor
Alison G Hoppin, MD


Infants with a congenital discrepancy between external genitalia, gonadal, and chromosomal sex are classified as having a disorder of sex development. A 2006 consensus conference suggested that the potentially pejorative terms "pseudohermaphrodite," "hermaphrodite," and "intersex" be replaced by the diagnostic category "disorders of sex development" (DSD) [1]. Although the term DSD has been accepted by the medical community, patients and support groups question its usefulness and appropriateness based on three criticisms: first, that DSD is an overly broad term that applies to conditions in which no sexual/gender disruption are expected (eg, Turner syndrome, Trisomy X, many females with congenital adrenal hyperplasia [CAH], and others); second, that the use of the word 'disorder' is seen as pejorative by some; and third, that an umbrella term like DSD lacks sufficient specificity to be helpful diagnostically, and is therefore unnecessary. Many of these groups do not accept the DSD designation and feel that it should be abandoned by the medical community. Until a consensus is reached on this issue, we will use the term DSD but will employ it only in relation to those patients in whom there is altered physical sexual differentiation (conditions previously captured by the term "intersex"). Many of these individuals present as newborns with an atypical genital appearance often termed "ambiguous genitalia." We will not use DSD to refer to conditions in which genital/gender discordance is not expected, such as Klinefelter syndrome, Turner syndrome, undescended testes, or most forms of hypospadias.

DSDs with genital abnormalities sufficient to prompt evaluation occur in approximately one in 1000 to 4500 live births [2-4]. Manifestations may include bilateral cryptorchidism (picture 1), perineal hypospadias with bifid scrotum (picture 2), clitoromegaly (picture 3A-B), posterior labial fusion (picture 4), phenotypic female appearance with a palpable gonad (with or without inguinal hernia) (picture 5), or hypospadias with a unilateral nonpalpable gonad (picture 6A-B). DSDs also include infants with discordant genitalia and sex chromosomes (picture 7). 46,XY infants with palpable gonads and simple hypospadias or microphallus, although undervirilized, do not have truly atypical genitalia and are discussed separately. (See "Clinical features and diagnosis of male hypogonadism" and "Hypospadias".)

The evaluation of the infant with a DSD is presented here. The management of such infants, which is critical and often controversial in the absence of well-defined outcome-based guidelines, is discussed separately. (See "Management of the infant with ambiguous genitalia".)


A logical approach to the infant with a disorder of sex development (DSD) requires a basic understanding of normal human sexual differentiation. This process is reviewed here briefly and discussed in detail elsewhere. (See "Normal sexual development".)

In early fetal development, both XX and XY fetuses have similar reproductive structural anlage; this period is referred to as the sexually indifferent phase of sexual development. This ambisexual state continues until the formation of the bipotential gonad at seven weeks, when fetuses bearing a Y chromosome begin developing testes, thereby becoming sexually distinct from fetuses without a Y chromosome. Normal ovarian development also requires active genetic pathways. Thereafter, gonadal differentiation and function determines the genital phenotype. Multiple genes contribute to normal sexual differentiation; mutations in these genes can lead to various DSDs (table 1A-B).


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Literature review current through: Sep 2016. | This topic last updated: Aug 19, 2016.
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