Case report
A 16-year-old female who presented to adolescent gynaecology with primary amenorrhea. Her BMI was 23 with normal secondary sexual characteristics and no evidence of hematocolpos. Pelvic ultrasound revealed a peripubertal uterus with a thin endometrial lining; both ovaries were small and featureless, with no developing follicles. Further radiological imaging with MRI revealed a small anteverted uterus with follicular activity in the right ovary, but the left ovary was not clearly visualised.
Laboratory findings indicated elevated levels of Follicle-stimulating hormone (FSH), Luteinising hormone (LH) and female testosterone. The 17-beta oestradiol, Free androgen index (FAI), thyroid and prolactin levels were within normal range. Karyotype analysis identified a 46 XY genotype; therefore, she was referred to the regional genetics service, which confirmed a diagnosis of Swyer’s Syndrome (Gonadal dysgenesis).
Due to the potential for malignant transformation of the underdeveloped gonads, she was counselled to undergo surgical removal of the ovaries. At an initial operation, the left ovary was not identified; therefore, a laparoscopic bilateral salpingectomy and only a right oophorectomy were performed. She underwent a further robotic minimal access surgical exploration of the left pelvic side wall and excision of residual streak gonadal tissue at the regional oncology centre. The regional gynaecology oncology and specialist (germ cell) multidisciplinary team (MDT) were involved in her management. The histopathology of the specimens removed at the two surgical procedures showed gonadoblastoma. She is currently on a combined oral contraceptive pill (COCP) akin to hormone replacement therapy (HRT) for cardiovascular disease and osteoporosis risk reduction. She remains under ongoing follow-up with the adolescent gynaecology clinic.
Discussion
Swyer syndrome (46XY complete gonadal dysgenesis) was first described by Swyer in 1955 as a condition where individuals with a 46XY karyotype develop female external genitalia but lack functional gonads [1]. The underlying genetic cause is usually a mutation or deletion in the SRY gene, which encodes the testis-determining factor(TDF) critical for testicular differentiation [2].
The absence of functional testes in individuals with a male genetic composition leads to a female phenotype with streak gonads, resulting in infertility, primary amenorrhea, and an increased risk of gonadal malignancies.
The incidence of Swyer syndrome is estimated to be 1 in 30,000 to 1 in 100,000 live births, often diagnosed during adolescence when individuals fail to menstruate [3].
These streak gonads, while capable of some limited cellular activity, are non-functional and pose a risk for the development of germ cell tumours, which can occur in up to 30% of individuals with this condition, including dysgerminomas and gonadoblastomas [4,5]. The risk of tumour formation increases with age, particularly post-puberty, underlining the importance of early gonadectomy [6].
The majority of individuals with Swyer syndrome present with primary amenorrhea, typically around the age of 15 to 16 years. There is a complete absence of menstruation and secondary sexual characteristics such as breast development and pubic hair. A pelvic ultrasound or MRI often reveals streak gonads and a small uterus [7]. Endocrine evaluation typically reveals hypergonadotrophic hypogonadism, with elevated gonadotropins like FSH, LH, and sex steroid levels(estradiol, testosterone) within the low-normal female reference range.[8].
Genetic testing is critical to confirm the diagnosis, revealing a 46XY karyotype despite the presence of a female phenotype [9]. This definitive diagnostic step is essential for distinguishing Swyer syndrome from other disorders of sexual development (DSDs).
Swyer syndrome is a rare but clinically significant condition that requires early diagnosis and multidisciplinary management. Gonadectomy, hormone replacement therapy, and psychosocial support are integral components of care. Advances in ART provide fertility options, and regular follow-up is necessary to monitor for malignancy and optimise long-term health outcomes.
Early intervention, including gonadectomy and hormone replacement therapy (HRT), is essential to mitigate the risk of malignancy and to support sexual and reproductive health. (HRT) is initiated to induce breast development, maintain bone health, and support cardiovascular function(10).
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