[MIM 300 068]

(formerly: feminizing testicle)

Estimated incidence between 1/20,000 and 1/99,000 live births of boys. 46,XY disorder of sexual development. X-linked recessive transmission or de novo mutation (30 %) of the AR gene (Xq11-12) coding for AR. AR, androgen receptor, is a nuclear transcription factor with three functional domains. Mutations are spread across the gene and predominate in five of the eight exons that code for the binding domain.

Complete insensitivity to androgens is linked to a mutation that completely suppresses protein function; target cells do not respond to testosterone or dihydrostosterone. It produces the phenotype of the "feminizing testicle" (Morris syndrome).

Clinical presentation:

-        childhood: inguinal hernia containing a testicle in a young girl.

-        puberty, the development of the breast is normal, but pubic and axillary hair is non-existent or sparse. Female external genitalia are normal, but female internal genitalia are absent. Tall stature in adulthood.

-        primary amenorrhea

-        incidentally, when there is a discrepancy between the chromosomal sex identified in the prenatal period (XY) and the female phenotype at birth.

A gonadectomy is proposed before adulthood because of an increased risk of germ cell tumor: seminoma, dysgerminoma or carcinoma in situ followed by gonadoblastoma.

Partial insensitivity to androgens (also known as Lubs [MIM 300 068], Goldberg-Maxwell, Reifenstein [MIM 312 300] syndrome) is due to a partial response of the androgen receptor and is most often diagnosed:

-        in a newborn with atypical genital development: hypospadias, cryptorchidism, micropenis, or even a female phenotype with clitoral hypertrophy

-        isolated micropenis or isolated gynecomastia,

-        pubertal virilization in a young girl

-        male fertility disorders

Moderate insensitivity to androgens is due to a mutation in the androgen receptor gene: it occurs in the form of male fertility disorders but without urogenital abnormalities. This abnormality is sometimes associated with Kennedy's disease (see this term).

The differential diagnosis of all these abnormalities of sexual development includes

-        a deficiency in androgen production: type 3 17-beta-hydroxysteroid dehydrogenase deficiency, hypoplasia of Leydig's cells, complete 46,XY gonadal dysgenesis (Swyer syndrome), 5-alpha reductase type 2 deficiency, mutations of the LH receptor, and variants of congenital adrenal hyperplasia (see these terms)

-        a genetic abnormality: Klinefelter, Denys-Drash, Frasier or Smith-Lemli-Optiz syndromes

Anesthetic implications:

none except for corticosteroid therapy if it is a variant of congenital adrenal hyperplasia

References :

-        Hugues IA, Davies JD, Bunch TI, Pasterki V, Mastroyannopoulou K, MacGougall J.
Androgen insensitivity syndrome.
The Lancet 2012; 380: 1419-28.

Updated: January 2020