Journal of Infertility and Reproductive Biology, 2015, Volume 3, Issue 1, Pages: 160-164 160 Clinical diagnosis and management of Swyer syndrome exhibiting different genetic variants: Current review of the literature Serkan Kahyaoglu Department of Reproductive Endocrinology, Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara, Turkey Abstract All genetical causes of pure gonadal dygenesis, Swyer syndrome, have not been discovered yet. Clinical and molecular studies are needed to identify novel genetic alterations that result in this type of sexual differentiation disorder. Swyer syndrome is a rare form of gonadal dysgenesis syndromes characterized with a 46, XY karyotype. A non-functional Y chromosome caused by various genetic mutations results in a deficient testis determining pathway and cessation of AMH and androgen secretion. As a result, normally developed mullerian structures (upper two thirds of vagina, cervix, uterus and fallopian tubes) stand by nonmasculinized internal and external genitalia. Several genes are involved in the process of sex differentiation, including SRY, RSPO1, SOX9, NR5A1, WT1, NR0B1 and WNT4. Among genetic mutations resulting with a deficient testis determining pathway, for 10-15% of patients a mutation that inactivates the SRY gene located on the long arm of Y chromosome is the ethiological factor. Defect in a different testis determining factor (TDF) such as the SF-1 gene is proposed as another etiological factor resulting with Swyer syndrome. The absence of known mutations in the SRY gene indicates that molecular defects could be present in the untranslated regulatory regions of the SRY gene or presence of other deficient gene(s) could explain the disorder. A phenotypically female patient presenting with primary amenorrhea, delayed puberty, normal internal genitalia except streak gonads and hypergonadotropic hyponadism should be evaluated by advanced genetic investigations to discover novel mutations for pure gonadal dysgenesis. Keywords: Swyer syndrome, Amenorrhea, Gonadoblastoma, Streak gonad, Disorders of sex development, Y chromosome 1. Introduction 1.1. Definition of Swyer syndrome Sexual differentiation depends upon a series of complex events. Variations in any of the pathways affecting gonadal differentiation can lead to conditions called disorders of sex development (DSDs) where the phenotype and genotype are discordant. A previous statement that was simultaneously published in Europe and the United States States revealed that previous terms such as intersex, hermaphrodite and sex reversal should be abandoned (1, 2). Instead, the term (DSDs) has been proposed to * Corresponding Adrress: Serkan Kahyaoglu, Department of Reproductive Endocrinology, Yenimahalle-Ankara, Turkey. Tel: +905058868040, E-mail: mdserkankahyaoglu@gmail.com replace these terms and DSDs have been categorized into 46,XX DSD; 46,XY DSD and chromosomal DSD according to their chromosomal component (3). These disorders may have some aspects such as infertility and the need for feminising surgery or gonadectomy. Genetic sex is determined at conception, when the ovum is fertilised by aspermatozoa containing X or Y chromosome. The presence of the Y chromosome will direct testicular development, through a switch gene called sex determining region of Y (SRY) gene present on its short arm (4). SRY gene coordinated with other testes determining factors (TDFs), influences the differentiation of the undifferentiated gonad into testicular tissue (5). The hormones produced by testicular tissue promote further genital