Reifenstein Syndrome

A syndrome characterized by hypogonadism as a result of a defect in androgen receptor. Often described as the male pseudohermaphrodism, presenting with hypospadias, gynecomastia, normal XY karyotype, and a pattern X-linked recessive inheritance.

Partial Androgen Insensitivity; Gynecomastia-Hypospadias Syndrome; Hereditary Familial Hypogonadism; Male Pseudohermaphroditism.

Two types have been suggested: Type I refers to the familial incomplete male pseudohermaphrodism and Type II is the autosomal recessive.

Undetermined; however, it is certainly common because of its often mild and variable features.

X-linked recessive.

Underlying defect is the partial deficiency of androgen receptors (AR), causing partial androgen resistance, and not because of a lack of androgen synthesis.

Clinical features (hypogonadism); family history; elevated plasma luteinizing hormone and testosterone levels; oligospermia or azoospermia; testis biopsy show normal Leydig and Sertoli cells but immature germinal cells and no spermatozoa; cultured fibroblast from genital skin show reduced levels of androgen receptor present with decreased cytoplasmic dihydrotestosterone binding capacity. The normal chromosomal study (46,XY) and normal testosterone conversion enzyme study (particularly 5-reductase level) exclude other causes of androgen resistance.

The phenotype is quite variable as a consequence of the partial sensitivity of the androgen receptors. In its mildest form, the man is infertile but otherwise normal. In its most severe form, the male pseudohermaphrodite may have hypospadias, cryptorchism, bifid scrotum, microphallus, atrophic ectopic testes, pseudovagina, gynecomastia, and absent vas deferens. Axillary and pubic hair is usually normal but chest and facial hair are minimal. Temporal recession of hairline is minimal and the voice is prepubertal in character. Azoospermia is common and occasionally accompanied by hypoplasia of vas deferens. Most have a male psychological development. Germ cell malignancies can occur.

There are no reported consideration for this disorder. However, supplemental steroid administration perioperatively might be indicated.

17-Beta Hydroxysteroid Dehydrogenase Deficiency (17-Ketosteroid Reductase Deficiency; 17-Beta HSD) presents clinically as male pseudohermaphroditism associated with significant enlargement of the adrenal glands and production of steroids impaired. It is inherited as either autosomal recessive or X-linked recessive.

17-Alpha Hydroxylase Deficiency presents in adolescence because of failure of the adrenal gland and testes to produce androgens. Because males are not exposed to androgens during fetal development they are born with female external genitalia. Failure to menstruate or to develop secondary sexual traits such as breasts or body hair, hypertension, and hypokalemia are characteristic.

3-Beta Hydroxysteroid Dehydrogenase Deficiency (3-Beta-HSD) is present at birth and leads to death within the first few hours. Glucocorticoids and mineralocorticoids are not produced. Boys are born with female or ambiguous external genitalia. A few patients with incomplete forms of this disorder may only be detected later in childhood or adulthood. Menstruation may occur between the ages of 4 and 8, the clitoris is enlarged, acne and advanced maturation of the skeleton may be seen in young children as well as hirsutism.