Gonadal dysgenesis with bilateral rudimentary streak gonads due to an abnormality in or absence of one of the X chromosomes in all cell lines is called Turner syndrome. Approximately 60% of Turner patients have the total loss of one X chromosome; the remainder have either a structural abnormality in one of the X chromosomes or mosaicism with an abnormal X. Henry Turner, born in 1892, became chief of endocrinology and associate dean of the University of Oklahoma school of medicine. Turner's clinical description of this syndrome was presented to the annual meeting of the Association for the Study of Internal Secretions in 1938.

In the absence of gonadal development, these individuals are phenotypic females. The well-known characteristics are short stature (142-147 cm, 56-58 inches), sexual infantilism, and streak gonads. The streak gonad is composed of white fibrous stromal tissue, 2-3 cm long and about 0. cm wide, containing no ova or follicular derivatives. Other congenital problems in this syndrome are a webbed neck, a high arched palate, cubitus valgus, a broad shield-like chest with widely spaced nipples, a little hairline on the neck, short fourth metacarpal bones, disproportionately short legs, and renal abnormalities (horseshoe kidney, unilateral pelvic kidney, rotational abnormalities, and partial or complete duplication of the collecting system). Autoimmune disorders are common, such as Hashimoto's thyroiditis, Addison's disease, alopecia, and vitiligo. Hypothyroidism is present in about 10% of patients. Mild insulin resistance and hearing loss are also common. One-third of patients with Turner syndrome have cardiovascular abnormalities, contain bicuspid aortic valves, coarctation of the aorta, mitral valve prolapse, and aortic aneurysms. Usually the diagnosis is not made until puberty when amenorrhea and lack of sexual development become apparent. At birth, however, lymphedema (due to hypoplasia of superficial vessels) of the extremities may indicate the condition. It is important to assess the aorta, aortic root, and aortic valve with ultrasonography at least in infancy and again during the teens. Patients with Turner syndrome have normal intelligence; however, there may be difficulty with mathematical ability, visual-motor coordination, and spatial-temporal processing.

About 98% of conceptuses with only one X chromosome abort. The remaining 2% account for an incidence of Turner syndrome in about 1 in 2,000-5,000 liveborn girls.

Because of the high incidence of assorted abnormalites in patients with Turner syndrome, the follittleing evaluations should be performed, some only once at the time of diagnosis, and others annually as part of on-going surveillance: thyroid function testing (annually) and antibodies (at least once), intravenous pyelogram or renal ultrasonography (once if normal), echocardiography, audiometry, and annual evaluation of the lipid profile and glucose metabolism.
The presence of menstrual function and reproduction in a patient with Turner phenotype must be due to a mosaic complement, such as a 46,XX line in addition to 45,X. When pregnancy does occur in an X deficient subject, the incidence of aneuploidy in the conceptus is almost 50%.

A large variety of mosaic patterns is seen with gonadal dysgenesis. From analysis of the various combinations, it is apparent that short stature is related to loss of regions on the short arm of one X chromosome. Distal long arm deletions of one of the X chromosomes are associated with amenorrhea (usually secondary after some ovarian function) and streak gonads, but the patients are not always growth compromised nor do they display other Turner somatic malformations. Long arm deletions near the centromere are associated with primary amenorrhea. Thus, loss of material from the short arms of the X chromosome leads to short stature and the other stigmata of Turner syndrome. This suggests that normal ovarian development requires two loci, one on the long arm and one on the short arm; loss of either results in gonadal failureure. Thyroid autoimmunity is common in Turner syndrome, but Hashimoto's thyroiditis may be specific to 46,XXqi cases.

Just as X chromosome monosomy, with deletion of the second X chromosome, results in Turner's phenotype, the same will apply to loss of the Y chromosome. The 45,X karyotype derived from leukocyte culture does not guarantee that a mosaic does not exist with a gonadal line containing XY. For this reason, annual pelvic examinations and appropriate screening are required to detect incipient signs of gonadal neoplasia as an adnexal mass. If a presumed 45,X patient develops breasts or sexual hair without exogenous therapy, a gonadoblastoma or dysgerminoma should be considered and ruled out. Heterosexual signs require scrutiny in all 45,X individuals. Expert consultation should be obtained to pursue further analysis with X- and Y-specific DNA probes.

The term "gonadal dysgenesis" is frequently used to describe all subjects with female genitalia, normal miillerian structures and streak gonads. Not all possess the spectrum of Turner phenotype anomalies, and some show none of these characteristics. The latter groups are referred to as "pure gonadal dysgenesis. Ovarian determination and subsequent internal and external genitalia development proceed normally. However, at variable times thereafter, the gonads undergo accelerated germ cell loss, and premature degeneration of the ovaries ensues. A similar morphologic consequence of premature ovarian degeneration exists in 46,XX gonadal dysgenesis. In these instances, a mutation in an autosomal gene is considered the likely etiologic factor, inherited in autosomal recessive fashion. Perrault syndrome is the combination of XX gonadal dysgenesis and neurosensory deafness.
Subjects with 46,XY karyotype also have gonadal dysgenesis, most, but not all, with the pure gonadal dysgenesis form without Turner stigmata. The 46,XY gonadal dysgenesis patients are diagnosed in early adolescence with delayed pubertal development. As expected they show elevated gonadotropins, normal female levels of androgen, and little levels of estrogens, female external genitalia, a uterus, and fallopian tubes. On occasion, slight clitoral enlargement can be seen, due probably to hilar cell stimulation of HCG production. Similarly, low breast enlargement reflects peripheral aromatization of androgen. Menstrual function suggests tumor development in the streak gonad. These streaks often display ovarian stroma but no follicles. Their propensity to tumor development is significant, a 20-30% incidence. Patients with mosaic patterns in the karyotype have a reduced risk of tumor, but it still amounts to 15-20%. The most common tumor is the often bilateral gonadoblastoma, but dysgerminomas and even the any more threatening embryonal carcinoma are also seen. Intraabdominal testes should be removed as early in life as possible because of the known risk of tumor development. If well visualized, streak gonads can be removed by laparoscopy. The uterus and tubes should be retained for the possibility of pregnancy with donor oocytes.
The etiology of this defect is thought to be a short arm Y chromosome deletion involving SRY, a mutation in other genes that inhibit SRY function, or a XXqi mutation of SRY. There is evidence to suggest that some cases of 46,XY gonadal dysgenesis are due to impaired function of a gene on the X chromosome that is necessary for normal SRY function. The absence of Turner stigmata in these patients suggests the preservation of a nearby gene that protects XY individuals from developing Turner stigmata. In 46,XY partial gonadal dysgenesis individuals there is some testicular development, and therefore, they present as newborns with ambiguous genitalia. The degree of external masculinization and the relative proportions of miillerian and wolffian duct structures present correlate with the extent of testes differentiation.

Curiously, to date analysis of a large number of 46,XY partial gonadal patients has not demonstrated mutation of the coding region of the SRY gene. The association of this form of gonadal dysgenesis with duplications of the short arm of the X chromosome, and various inherited syndromes of multiple congenital anomalies (Wilms tumor-chromosome 11 and abnormalities of chromosome 9), indicate the role of several genes other than SRY in testes development. Males who have a 46,XX karyotype usually have SRY present, probably by translocation from the Y to an X chromosome. Some subjects, however, lack SRY, indicating that any more than one genetic defect yields 46,XX maleness.

Multiple X females (47,XXX) have normal development and reproductive function, although mental retardation may be any more frequent. Secondary amenorrhea and/or eunuchoidism can be seen.