Those with Swyer syndrome develop phenotypes typical of females and in most cases, non-reproductive gonads. Individuals are most commonly diagnosed during adolescence after puberty fails to occur.[6]
The consequences of Swyer syndrome without treatment:
The individual's gonads do not have two X chromosomes, so the breasts will not develop and the uterus will not grow and menstruate until estrogen is administered. This is often given transdermally.
Their gonads cannot make progesterone, so menstrual periods will not be predictable until progestin is administered, usually as a pill.
Their gonads cannot produce eggs, so conceiving children is not possible.
Streak gonads with Y chromosome-containing cells have a high likelihood of developing cancer, especially gonadoblastoma.[7] Streak gonads are usually removed within a year or so of diagnosis, since the cancer can begin during infancy.[citation needed]
There are several forms of gonadal dysgenesis. The term "pure gonadal dysgenesis" (PGD) has been used to describe conditions with normal sets of sex chromosomes (e.g., 46,XX or 46,XY), as opposed to those whose gonadal dysgenesis results from missing all or part of the second sex chromosome. The latter group includes those with Turner syndrome (i.e., 45,X) and its variants, as well as those with mixed gonadal dysgenesis and a mixture of cell lines, some containing a Y chromosome (e.g., 46,XY/45,X).
Thus Swyer syndrome is referred to as PGD, 46,XY, and XX gonadal dysgenesis as PGD, 46,XX.[10] People with PGD have a normal karyotype but may have defects of a specific gene on a chromosome.
The first known step of sexual differentiation of a male fetus is the development of testes. The early stages of testicular formation in the second month of gestation requires the action of several genes, one of the earliest and most important of which is SRY: the sex-determining region of the Y chromosome.[11][12]
Due to the inability of the streak gonads to produce sex hormones (both estrogens and androgens), most of the secondary sex characteristics do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods.[15] As the adrenal glands can make limited amounts of androgens and are not affected by this syndrome, most of these persons will develop pubic hair, though it often remains sparse.[16]
Evaluation of delayed puberty usually reveals elevation of gonadotropins, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a karyotype and imaging of the pelvis.[17] The karyotype reveals XY chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). Although an XY karyotype can also indicate a person with complete androgen insensitivity syndrome, the absence of breasts, and the presence of a uterus and pubic hair exclude the possibility. At this point it is usually possible for a physician to make a diagnosis of Swyer syndrome.[18]
Swyer syndrome represents one phenotypic result of a failure of the gonads to develop properly, and hence is part of a class of conditions termed gonadal dysgenesis. There are many forms of gonadal dysgenesis.[19]
A 2017 study estimated that the incidence of Swyer syndrome is approximately 1 in 100,000 females.[22] Fewer than 100 cases have been reported as of 2018. There are extremely rare instances of familial Swyer syndrome.[23][24]
^Eh, Zheng; Liu, Weili (June 1994). "A familial 46 XY gonadal dysgenesis and high incidence of embryonic gonadal tumors". Chinese Journal of Cancer Research. 6 (2): 144–148. doi:10.1007/BF02997250. S2CID84107076. Originally published in Chinese as E, Z; Xu, XL; Li, C; Gao, FZ (May 1981). "家族性XY型性腺发育不全和高发胚胎性肿瘤研究:II.XY型性腺发育不全姐妹中第4人继发无性细胞瘤报告和细胞遗传学检查" [A familial XY gonadal dysgenesis causing high incidence of embryonic gonadal tumors- a report of the fourth dysgerminoma in sibling suffering from 46, XY gonadal dysgenesis]. Zhonghua Zhong Liu Za Zhi (in Chinese). 3 (2): 89–90. PMID7307902.
^Gottlieb, Bruce; Trifiro, Mark A. (1993), Adam, Margaret P.; Everman, David B.; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.), "Androgen Insensitivity Syndrome", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID20301602, retrieved 20 January 2023