Turner syndrome
- Complete/partial absence of one X chromosome (45, XO)
- Short stature, webbed neck, broad chest
- Females often do not undergo puberty
- Infertility (due to ovarian dysgenesis), risk of cardiovascular and kidney abnormalities
Klinefelter syndrome
- Males with an extra X chromosome (47, XXY)
- Tall stature, reduced muscle mass, gynecomastia, sparse body hair
- Testicular atrophy (shrinking)
- Infertility (due to impaired spermatogenesis), risk of breast cancer and osteoporosis
Altered FSH release
- Altered FSH levels can affect puberty and reproductive functions
- In females, FSH stimulates ovarian follicle growth
• Abnormal FSH levels result in irregular menstrual cycles and infertility
- Males: FSH stimulates spermatogenesis
• Abnormal FSH levels lead to reduced sperm production
SRY gene
- Sex-determining region Y gene, located on the Y-chromosome
- Initiates testis determination, leading to androgen secretion and male differentiation
- Presence of SRY → testicular development → fertile, typical puberty
- Absence of SRY → ovarian development
Swyer syndrome
- SRY mutation 1
- 46, XY individuals, but phenotypically female
- Due to failure in testicular development
- Female external genitalia
- Lack of functional ovaries
- Absence of uterus and fallopian tubes
- Infertile due to lack of functional ovaries
- Oestrogen replacement therapy is necessary for sexual development, bone health
SRY translocation
- SRY is normally located on the Y chromosome
- Translocation to the X chromosome can cause disorders of sex development
, - Infertility, risk of gonadal tumours
- Gender identity issues
- If a foetus is conceived from a sperm cell with an X chromosome bearing the SRY gene,
it will develop as a male despite not having a Y chromosome
De la Chapelle syndrome
- Translocation of SRY to an X chromosome
- 46, XX individuals, but phenotypically male
- Male external genitalia with testicular development
- Normal fertility if testes are present
- Hormone replacement therapy is possibly needed for masculinization and secondary
sexual characteristic development
X-inactivation
- Random silencing of one of the two X chromosomes in females
- Xist initiates inactivation, Tsix negatively regulates Xist expression
- The chromosome remains inactive throughout cell divisions. If Tsix fails to suppress
Xist on the intended active X chromosome, both X chromosomes may be partially
inactivated or fail to inactivate properly, leading to abnormal gene dosage effects
- Primary sex characteristics: Disrupted normal ovarian development and function
- Secondary sex characteristics: Underdeveloped, irregular or absent menstrual cycles,
delayed puberty
- Genetic females (XX) with disrupted X-inactivation typically identify as female, but
abnormalities can affect gender expression due to hormonal imbalances
- Reduced fertility or infertility (due to disrupted ovarian function)
- Physical and intellectual development are affected if critical genes on X chromosomes
are not properly regulated
Androgen insensitivity syndrome (AIS)
- Mutation in the androgen receptor gene on the X chromosome
- Individuals with AIS typically have a 46, XY karyotype
- Inability of androgens to exert their effects, resulting in incomplete masculinization
- Male:
• Male genotype (46, XY)
• Undescended/incompletely descended testes due to lack of response to androgens
• Typically female external genitalia, sparse body hair, and breast development at
puberty due to aromatization of androgens to oestrogens
• Infertile
