46,XX<unk>  46,XX<unk>  is characteristic of female hypogonadism with a karyotype of 46,XX. Streak ovaries are present with non-functional tissues unable to produce the required sex steroid oestrogen. Low levels of oestrogen effect the HPG axis with no feedback to the anterior pituitary to inhibit the secretion of FSH and LH. FSH and LH are secreted at abnormal elevated levels. Improper levels of these hormones will cause a failure to initiate puberty, undergo menarche, and develop secondary sex characteristics. If sufficient functional ovarian tissue is present, limited menstrual cycles can occur. The pathogenesis of 46,XX<unk>  is unclear, as it can manifest from a variety of dysregulations. Interruption during ovarian development in embryogenesis can cause 46,XX<unk>  with cases of abnormalities in the FSH receptor and mutations in steroidogenic acute regulatory protein (StAR protein) which regulates steroid hormone production. 46,XY<unk>  46,XY<unk>  is characteristic of male hypogonadism with karyotype 46,XY. In embryogenesis, the development of the male gonads is controlled by the testis determining factor located on the sex-determining region of the Y chromosome (SRY). The male gonad is dependent on SRY and the signalling pathways initiated to several other genes to facilitate testis development. The aetiology of 46,XY<unk>  can be caused by mutations in the genes involved in testis development such as SRY, SOX9, WT1, SF1, and DHH. If a single or combination of these genes are mutated or deleted, downstream signalling is disrupted, leading to malformation of male external genitalia. SRY acts on gene SOX9 which drives Sertoli cell formation and testis differentiation. An absence in SRY causes SOX9 to not be expressed at the appropriate time or concentration, leading to a deficiency in testosterone and anti-Müllerian hormone production. Inadequate levels of testosterone and anti-Müllerian hormone disrupts the development of Wolffian ducts and internal genitalia that are key to male reproductive tract development. The lack of the male associated steroid hormones drives Müllerian duct development and promotes the development of female genitalia.<unk>  streaks replace the tissues of the testes, resembling ovarian stroma absent of follicles. 46,XY<unk>  can remain unsuspected until delayed pubertal development is observed. Approximately 15% of cases of 46,XY<unk>  carry de novo mutations in the SRY gene, with an unknown causation for the remaining portion of 46,XY<unk>  patients. Mixed<unk>  Mixed<unk> , also known as X0/XY mosaicism or partial<unk> , is a sex development disorder associated with sex chromosome aneuploidy and mosaicism of the Y chromosome. Mixed<unk>  is the presence of two or more germ line cells. The degree of development of the male reproductive tract is determined by the ratio of germ line cells expressing the XY genotype. Manifestations of mixed<unk>  are highly variable with asymmetry in<unk>  development of testis and streak gonad, accounted for by the percentage of cells expressing XY genotype. The dysgenic testis can have adequate functional tissue to produce satisfactory levels of testosterone to cause masculinisation. Mixed<unk>  is poorly understood at the molecular level. The loss of the Y chromosome can occur from deletions, translocations, or migration failure of paired chromosomes during cell division. The chromosomal loss results in partial expression of the SRY gene, giving rise to abnormal development of the reproductive tract and altered hormone levels. Turner syndrome Turner syndrome, also known as 45,X or 45,X0, is a chromosomal abnormality characterised by a partial or completely missing second X chromosome, giving a chromosomal count of 45, instead of the typical count of 46 chromosomes. Dysregulation in meiosis signalling to germ cells during embryogenesis may result in nondisjunction and monosomy X from separation failure of chromosomes in either the parental gamete or during early embryonic divisions. The aetiology of Turner syndrome phenotype can be the result of haploinsufficiency, where a portion of critical genes are rendered inactive during embryogenesis. Normal ovarian development requires these vital regions of the X chromosome that are inactivated. Clinical manifestation include primary amenorrhea, hypergonadotropic hypogonadism, streak gonads, infertility, and failure to develop secondary sex characteristics. Turner syndrome is not diagnosed until a delayed onset of puberty with Müllerian structures found to be in infantile stage. Physical phenotypic characteristics include short stature, dysmorphic features and lymphedema at birth. Comorbidities include heart defects, vision and hearing problems, diabetes, and low thyroid hormone production. Endocrine disruptions Endocrine disruptors interfere with the endocrine system and hormones. Hormones are critical for the correct events in embryogenesis to occur. Foetal development relies on the proper timing of the delivery of hormones for cellular differentiation and maturation. Disruptions can cause sexual development disorders leading to<unk> .
Gonadal dysgenesis
Thyroid dysgenesis
XY gonadal dysgenesis
Cryptorchidism
Primordial dwarfism
Müllerian agenesis
Renal agenesis
Supernumerary kidney