Those with Swyer syndrome develop phenotypes typical of females and nonfunctional ovaries. Individuals are most commonly diagnosed during puberty after menstruation fails to occur (primary
amenorrhea).[3]
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 without
embryo transfer. There has been a case of unassisted pregnancy in one woman with XY gonadal dysgenesis, who had a predominantly 46,XY karyotype – a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X), and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X) – who gave birth to a 46,XY female with complete gonadal dysgenesis.[4]
Streak gonads with Y chromosome-containing cells have a high likelihood of developing cancer, especially
gonadoblastoma.[5] Streak gonads are usually removed within a year or so of diagnosis, since the cancer can begin during infancy.[citation needed]
Seven other genes have been identified with probable associations that are as-yet less clearly understood.[7]
Pure gonadal dysgenesis
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.[8] People with PGD have a normal karyotype but may have defects of a specific gene on a chromosome.
Pathogenesis
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.[9][10]
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.[13] 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.[14]
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.[15] 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.[16]
Related conditions
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.[17]
Upon diagnosis,
estrogen and
progestogen therapy is typically commenced, promoting the development of female characteristics.
Hormone replacement therapy can also reduce the likelihood of osteoporosis.[1]
Epidemiology
A 2017 study estimated that the incidence of Swyer syndrome is approximately 1 in 100,000 females.[20] Fewer than 100 cases have been reported as of 2018. There are extremely rare instances of familial Swyer syndrome.[21][22]
History
Swyer syndrome was first described by G. I. M. Swyer in 1955 in a report of two cases.[21]
^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