Sex Development 11/4 Flashcards
- Describe the clinical characteristics of disorders of sex chromosomes.
Turner Syndrome X, 45 XO signs at birth: webbed neck, prenatal cystic hygroma, puffy hands and feet, heart defection like coarctaction of the aorta normal intelligence short stature infertility due to non-functioning ovaries hormone dysfunction low set ears, broad chest occurs in 1/2500 new born girls
Kleinfelters Syndrome XXY 47 Can be seen in childhood: learning disabilities, delayed speech/langauge, generally quiet small testes tall stature infertility reduced facial and body hair hypospadias occurs in 1/500 to 1/1000 newborns
Jacobs Syndrome XYY learning disabilities speech delays developmental delays behavioral and emotional difficulties autism spectrum disorders tall stature 1/1000 newborn boys
Triple X Syndrome XXX
may have tall stature
increased risk of learning disabilities, delayed speech, delayed motor milestones, seizures, kidney abnormalities
1/1000 newborn girls
AIS (Androgen Insensitive Syndrome)
46, XY
X-linked gene, AR
Mutation causes abnormality of the androgen receptor—testosterone is there but does not recognize as present
5-Alpha Reductase Deficiency
46, XY
Gene: SRD5A2
-mutation causes decreased ability of body to convert testosterone to dihydrotesterone
-phenotype shoes undervirilizedm ale with increased virilization at the time of puberty
Autosomal Recessive
Disorders associated with SRY gene
46 XY or 46 XX
Y-Linked gene (translocation onto X chromosome)
Deletion or absence of the gene results in the full 46, XY sex reverse in most cases, a phenotypically normal female
-Ectopic presence of the SRY gene in a 46, XX individual can result in a phenotypically normal male
-Mutations in the SRY gene in a 46, XY individual results in decreased or absent production of Anti Mullein hormone and under virilization of Male
-causes some fertility problems later in life but otherwise really hard to tell
Denys-Drash & fraiser syndrome: sex reversal with 46, XY due to mutations in the WT1 gene both cause different types of chronic kidney disease (diffuse mesangial sclerosis, focal segmental glomerulosclerosis) increased risk for Wilms tumor WT1- transcription factor for SRY gene
Congenital Adrenal Hyperplasia- Ambiguous genitalia in 46, XX, 21-hydroxylase deficiency
complicated by salt wasting in first few weeks of life and with times of metabolic stress—decreased sodium and chloride, increased potassium
- Describe the genetic regulation of sexual differentiation.
both ovaries and testes result from a common, biopotential gonad
blue/red bubbles in slide on “Genetic Regulation of sex differentiation”
We know a lot more about genes regulating development of the testes
Secondary sex determination: Gonadal development then determines secondary sex characteristics
—includes sex specific organs (penis, seminal vesicle, prostate gland)(vagina,cervix,uterus,fallopian tubes, mammary glands)
—also includes other phenotypic features (vocal cartilage, hair growth, musculature)
- Describe the basic embryology of dimorphic human reproductive organs.
4th week of conception: primordial germ cells form in wall of yolk sac
5th week: Coelomic epithelium becomes genital ridge
6th week of conception: primordial germ cells migrate to the dorsal mesentery of hind gut and enter the undifferentiated gonad
epithelial cells of gonadal ridge proliferate and form primitive sex cords
7th week: differentiation of genital ridge into (sertoli cells—orooduce sperm, and leydig cells—MALE ONLY)
8th week of conception: leydig cells begin producing testosterone, Sertoli cells produce Anti-mullerian hormone, primitive sex cords differentiate into testis cords and rate testes (MALE ONLY)
7th-8th week of conception: primitive sex cords dissociate into irregular clusters, medullary (primitive) cords regress and cortical (secondary) cords are formed—FEMALE ONLY
Difference in Mesonephric (Wollfian) and Paramesonephric (Mullerian) Duct—initially both are present
Men: Wolfing
Women: Mullerian
- Describe the clinical approach to disorders of sexual differentiation.
1st day of life: Obtain FISH studies for sex chromosomes and a karyotype (or chromosomal microarray), consider an ultrasound study to evaluate for gonads and uterus, and s surgical consult with urology
2nd day of life order hormone studies, LH, FSH, Testosterone, Dihydrotestosterone, +/- AMH (Anti Mullein Hormone)
Consider consultation with a specialized disorders of sexual developmental team, if available: Endocrinology, Genetics, Urology, Psychology
Issues to consider: Underlying genetics, family culture and social perspective, medical and surgical outcomes, risks for tumor development, fetal brain development in the context of hormone exposure/future gender identity, future sexuality, future fertility
There’s a pathway for figuring out the exact same of a baby, see the chart on slide 40
