Ambiguous genitalia

Ambiguous genitalia


Ambiguous genitalia refers to external genitalia that are not obviously of either sex, and includes: micropenis, clitoromegaly, microorchia, cloacal exstrophy, mixed gonadal dysgenesis, true hermaphroditism, agenesis of cervix, vagina.The primordial germ cells, which originate in the endoderm of the yolk sac during the eighth week, migrate to the genital ridge to form the indifferent gonads. These develop into testes if the embryo is 46,XY and are morphologically identifiable seven to eight weeks after conception. The Sertoli and Leydig cells function in dissociation from testicular morphogenesis. These two cell lines secrete hormones that direct subsequent male differentiation. Leydig cells produce an androgen, probably testosterone, that permits differentiation into the vasa deferentia, epididymis and seminal vesicles. Sertoli cells produce a glycoprotein known as AMH, believed to cause regression of mullerian derivatives (uterus and fallopian tubes). In the absence of AMH and testosterone, internal genitalia develop along female lines. Mullerian ducts develop into uterus and fallopian tubes; Wolffian ducts regress. In the absence of the Y chromosome, the indifferent gonad develops into an ovary at approximately 50-55 days of embryonic life. The process of external genitalia development also depends on the presence or absence of certain hormones. Leydig cells produce testosterone which stabilise Wolffian ducts, permitting differentiation into external male genitals. Without testosterone and AMH, female external genitalia develop; the uterus and fallopian tubes form from the Mullerian ducts. There are limited data on the overall incidence of ambiguous genitalia, but it may be about 1 to 2/10,000 live births. This figure will vary with ethnicity and underlying cause.


The diagnosis of ambiguous genitalia should be considered after careful evaluation of the perineum demonstrates a protruding genital tubercle, representing the clitoromegaly or micropenis, and midline fusion of the genital folds, representing labial fusion or cryptorchidism. The timing of this evaluation is important as the testes normally descend into the scrotum between 28 and 34 weeks. The diagnosis should be also considered when prenatal testing (CVS, amniocentesis) unequivocally demonstrates gender in disagreement with the sonographic findings. Underlying causes include a multiple congenital anomaly syndrome, in which a search for other major organ system anomalies should be sought, and biochemical defects such as congenital adrenal hyperplasia. In the latter, early prenatal diagnosis may allow for treatment with steroids to prevent virilisation.

Differential Diagnosis

Fetal limbs or coiling of the umbilical cord between the legs may obscure genital structure; colour flow doppler will clearly identify loops of umbilical cord. Oedema of the labia majora may produce a similar appearance to the scrotum.

Sonographic Features

Enlarged clitoris projecting between labia


Absence of penis

Presence of testes in scrotum provides accurate diagnosis of a male

Bifid scrotum with undescended testes

Associated Syndromes

  • Ablepharon-macrostomia
  • Androgen insensitivity
  • Aniridia-Wilms tumour association
  • Asplenia-cardiovascular anomaly caudal deficiency
  • Bardet-Biedl
  • Beemer
  • Biemond Type II
  • Bladder exstrophy seq
  • Congenital adrenal hyperplasia
  • Deletion 11q 
  • deletion 18q
  • Drash, Fraser
  • Kallmann
  • Laurence-Moon
  • Maternal androgens
  • Mixed gonadal dysgenesis
  • Mosaic syndromes with Y cell lines
  • Noonan
  • Opitz syndrome
  • Prader-Willi
  • Robinow syndrome
  • Rud
  • Septo-optic dysplasia
  • Short rib-polydactyly syndrome
  • Majewski type
  • Smith-Lemli-Opitz
  • Swyer syndrome
  • XY pure gonadal dysgenesis
  • Trimethadione
  • Triploidy
  • Trisomy 21
  • Trisomy 4p
  • True hermaphrodite
  • VATER Association
  • XXXY
  • XXY (Kleinfelter syndrome).


  1. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins J CIn: Prenatal Diagnosis of Congenital Anomalies Appleton and Lange: Norwalk, p. 304
  2. Fleischer, A, Romero R, Manning F, Jeanty P, James Jr A In: The Principles and Practice of Ultrasonography and Obstetrics and Gynecology, 4th Edition Appleton & Lange: Norwalk, p. 269
  3. Stevenson R, Hall T, Goodman R In: Human Malformations and Related Anomalies, Vol II Oxford U Press: NY, p551