TEMPLATE DESIGN © SWYER’S SYNDROME : A Case Report Ramli, I., Win Mar, J. & Salzihan, S. Universiti Sains Malaysia Clinical Features DiscussionsDiscussions (cont..) References Clinical History ; A 18 year-old Malay schoolgirl was referred from a general practitioner for “Primary Amenorrhoea”. On further questioning, there was no cyclical abdominal pain or any abdominal mass. There was no bowel or urinary symptoms. She had two sisters whom attained menarche at the age of 14 year-old. Her developmental history also was normal.There was no significant past medical or past surgical history. On Examination : Her height was 158 cm, weight 52 kg. No webbed neck. Her breast was underdeveloped ( Tanner Stage II ). There was no axillary hair. There was no palpable abdominal mass. Labia majora – normal but underdeveloped labia minora. The pubic hair was sparse. Hymenal ring present Vaginal opening was noted. Per rectal examination ?Hypoplastic uterus ?absence of cervix The risk of gonadoblastoma and dysgerminoma in women with Swyer syndrome has been estimated to be between 15 to 35%, and current practice is to perform bilateral gonadectomy as soon as the diagnosis is made. It is thought that gonadoblastomas arise from persisting undifferentiated gonadal tissue within the dysgenetic gonads. This tissue is similar in appearance to that found in the embryonic gonad prior to the expression of SRY gene and contains germ cells scattered in stroma and presertoli—granulosa cells. Gonadoblastoma is a form of neoplasm that almost exclusively develops in dysgenetic gonads, and it can occur at a young age. The median age at gonadectomy was 18 years (range 9–33 years). Histology of the gonad was available in 22 women and demonstrated streak gonads with no evidence of malignancy in 12, dysgerminoma in 7 and gonadoblastoma in 3. The youngest case reported in the literature was in a 9-monthold infant with ambiguous genitalia. The uterine size and shape was assessed in eight women after completion of induction of puberty, and the uterine cross-section was found to be significantly lower than that in normal controls. Fertility was achieved with ovum donation in three women, all of whom had live births and one subsequently had a second successful pregnancy. A multidisciplinary team of surgeons, endocrinologists, gynaecologists and psychiatrists should be involved in the procedure to optimize the psychosocial, social and surgical outcome. Early diagnosis of Swyer syndrome is necessary in view of the risk of dysgerminoma that can develop at an early age. Adequate hormone replacement is required to maintain bone mineral density and may improve the uterine size and shape. Investigations Hormonal assay: Serum FSH : 69.5 mIU/ml ↑ Serum LH : 25.5 mIU/ml ↑ Testosterone : 2.0 nmol/L ↓ Progesterone : 2.4 nmol/L ↓ Oestradiol : 43 pmol/L ↓ Prolactin : 334 uIU/ml Cytogenetic study; 46, XY [20] Cytogenetic analysis carried out in 20 metaphases showed 46,XY karyotype pattern SRY gene - present Laparoscopic findings: Uterus was hypoplastic, fibrocollagenous body was seen. Both fallopian tubes were normal. Streak gonads were seen both sides. The cervix was not visualised. Peritoneal surface was normal Proceeded to excision of gonadal tissues laparoscopically Swyer's syndrome is XY gonadal dysgenesis. Incidence 1:80,000 birth. A type of hypogonadism in which no functional gonads are present to induce puberty. Externally female person with XY chromosomes. The gonads are found to be partially non-functional streaks. Pathogenesis: The first known step of sexual differentiation of XY fetus is the development of testes. It requires the action of several genes. The earliest and most important is SRY genes. (sex-determining region of Y chromosome). Mutations of SRY genes account for many cases of Swyer syndrome. The indifferent gonads fail to differentiate into testes. Without testes, no testosterone or antimullerian hormone (AMH) are produced. Without testosterone the external genitalia fail to virilize, resulting in normal female genitalia Without AMH, the mullerian ducts developed to normal internal female organs. A baby who is externally a girl is born and is normal in all anatomic respects except that the girl has a non-functional streak gonads instead of ovaries or testes. A defect of the reproductive system typically unsuspected until puberty fails to occur. The appear to be normal girls and are generally considered so. Clinical Presentations : Delayed puberty – 90% Gonadoblastoma – 6% Diagnosis: Elevation of gonadotrophins Karyotyping Pelvic imaging The consequences of streak gonads : No oestrogen production The breasts will not develop The uterus will not grow No progestrone production No menstrual periods No ovum production Likelihood of developing gonadoblastoma Swyer syndrome: presentation and outcomes. L Michala,a D Goswami,b SM Creighton,a GS Conwaya a Department of Reproductive Health, UCL Institute for Women’s Health, Elizabeth Garrett Anderson Hospital, London, UK BJOG - 6 February 2008 Stoicanescu D, Belengeanu V, et al. (2006). "Complete Gonadal Dysgenesis With XY Chromosomal Constitution". Acta Endocrinologica (Buc) 2 (4): 465–70."Complete Gonadal Dysgenesis With XY Chromosomal Constitution"