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Flashcards in Disorders of the Sex Chromosomes Deck (47):

Chromosomal sex in males

Embryo with Xy sex chromosomes


Chromosomal sex in females

Embryo with XX sex chromosomes



An individual with both ovarian and testicular tissue


Female psueudohermaphrodite

An individual with 46, XX karyotype and nl ovarian tissue, but with ambiguous or male external genitalia
A derogatory term


Male pseudohermaphrodite

An individual with a 46, XY karyotype and nl testicular tissue but with ambiguous or female external genitalia
A derogatory term


What is important for determining the sex chromosome constitution of pts with ambiguous development of the external genitalia?

A karyotype


Disorders of Sex Development (DSD)

The term used to describe hermaphroditism and psuedohermaphroditism


Cause of female pseudohermaphroditism

Congenital adrenal hyperplasia (CAH), an inherited autosomal recessive disorder of hormone synthesis by the adrenal glands
Mutation of CyP21A2 that causes lack of 21-hydroxylase, needed by the adrenal gland to produce cortisol and aldosterone
The body produces more androgen


Tx for female pseudohermaphroditism

Medical, surgical and psychocsocial management is associated with improved fertility rates and nl female gender identity


Cause of male pseudohermaphroditism

Disorders of testis development during embryogenesis
Abnormalities of gonadotropins
Inhertited disorders of testosterone biosynthesis and metabolism
Abnormalities of androgen target cells


Androgen insensitivity syndrome

A mutation in the X-linked androgen receptor (AR) gene causes XY males to become phenotypic females
Gonads develop into testes and produce testosterone, dihydrotestosterone (DHT) and AMH
The body still responds to AMH, causing the female duct system to degenerate
The body cannot respond to testosterone and dHT because the AR gene is defective, so the male duct system degenerates and the genitalia develop as female structures


Dosage compensation

A mechanism that regulates the expression of sex-linked gene products
Human females have random inactivation of one X chromosome in all somatic cells to balance the expression of X-linked genes in males and females


Process of X chromosome inactivation

1. Pairing X chromosomes
2. Selecting which X chromosome to inactivate by expression of XIST gene (inactivated chromosome is coated with XIST RNA), located in a region of the X chromosome called the X inactivated center (Xic)
-XIST is only expressed from the inactive X chromosome and it serves to silence most (but not all) genes on the inactive X


Barr body

An inactivated X chromosome, tightly coiled
XY males have no inactive X chromosomes and no Barr bodies


Mosaicism in females

Some cells express the mother's X chromosome and some cells express the father's X chromosome
-Inactivated chromosome can come from either mother or father
-Inactivation occurs early in development
-Inactivation is permanent; all descendants of a particular cell have the same X inactivated


Hypohidrotic ectodermal dysplasia

Mutation in EDA gene
X-lined recessive
Affects skin, hair, nails, teeth, sweat glands
Females are mosaic bc of random X-chromosome inactivation


Twins and X-chromosome inactivation

Random X inactivation can cause twins with identical genotypes to have different phenotypes


What is the only stage of sex determination that is established at fertilization?

Chromosomal sex


What are the three levels of sexual determination?



Gonadal sex differentiation

For the first 7 or 8 wks, the embryo is neither male nor female
-Two undifferentiated gonads
-Both male and female reproductive duct systems develop
Genes cause gonads to develop as testes or ovaries, establishing gonadal sex


SRY gene

Sex-determining region of the Y chromosome
Located near the end of the short arm of the Y chromosome
Plays a major role in causing the undifferentiated gonad to develop into a testis



A steroid hormone produced by the testis
Male sex hormone
Stimulates development of the mesonephric ducts (formerly called Wolffian ducts) in the embryo; the male ducts


Anti-Mullerian hormone (AMH)

Hormone produced by developing testis that causes breakdown of the paramesonephric ducts (formerly called Mullerian ducts) in the embryo; the female ducts


Female development

Requires the absence of the Y chromosome (and SRY gene) and the presence of two X chromosomes
Embryonic gonad develops as an ovary
In the absence of testosterone, the mesonephric (Wolffian) duct system degenerates
In the absence of AMH, the paramesonephric (Mullerian) duct system forms female reproductive system


Gonadal sex of males

Sex-determining region of the Y chromosome (SRY) brings about development of undifferentiated gonads into testes
Testes secrete masculinizing hormones, including testosterone, a potent androgen


Gonadal sex of females

No Y chromosome, so no SRY. With no masculinizing influence, undifferentiated gonads develop into ovaries
No androgens secreted


Phenotypic sex of males

In presence of testicular hormones, undifferentiated reproductive tract and external genitalia develop along male lines.


Phenotypic sex of females

With no masculinizing hormones, undifferentiated reproductive tract and external genitalia develop along female lines


What are clinical indicators of a sex chromosome abnormality and the need for cytogenetic and molecular analyses?

Delayed onset of puberty
Ambiguous genitalia


What are the most common sex chromosome defects in liveborn infants?

Trisomies (XXY, XYY, and XXX) followed by monosomy for the X


What is required for development in the sex chromosomes?

At least one copy of the X chromosome
Increasing numbers of X or Y chromosomes causes progressively greater disturbances in phenotype and behavior


Klinefelter syndrome (47, XXY)

Chromosomal inheritance
Due to nondisjunction in maternal or paternal meiosis I; some have additional X chromosomes
1 in 500-1,000 male live births


Clinical features

Male phenotype, but may fail to develop nl secondary sex characteristics
Tall and thin, relatively long limbs
Small testes, produce few or no sperm
Some degree of breast development
Learning disabilities


Management of Klinefelter syndrome

Tx with testosterone
Counseling regarding probable infertility
Intervention to manage learning disabilities


Genetic counseling for Klinefelter

Recurrence is rare and can be detected by prenatal chromosomal analysis


47,XYY syndrome

Chromosomal inheritance
Due to nondisjunction in paternal meiosis II
1 in 1,000 male live births


Clinical features of 47,XYY syndrome

Male phenotype and fertile
Tend to have learning disabilities and behavioral problems
Relatively tall stature


Management of 47,XYY syndrome

Anticipatory guidance and support for learning disabilities


Genetic counseling for 47,XYY syndrome

Recurrence is rare and can be detected by prenatal chromosomal analysis. Transmission is rare


Trisomy X (47,XXX)

Chromosomal inheritance
Nondisjunction in maternal meiosis I
1 in 1,000 live births


Clinical features of Trisomy X

Female phenotype
Somewhat above average in stature
70% of pts have some learning problems


Management of Trisomy X

Anticipatory guidance and support for developmental impairment


Genetic counseling for Trisomy X

Recurrence is rare


Turner syndrome (45,X and variants)

Chromosomal inheritance
Due to nondisjunction or loss of a structurally abnormal X or Y chromosome
70-80% of pts conceived from sperm lacking a sex chromosome
Many are mosaics, with a cell line containing 46 chromosomes with a structurally abnormal X or Y
1 in 3,000-4,000 female live births


Clinical features of Turner syndrome

Female phenotype but fail to develop nl secondary sex characteristics
Short stature, primary amenorrhea and usually infertile
Coarctation of aorta, renal anomalies
Lymphedema common at birth, "webbing" of the neck
Nl intelligence but learning disabilities, esp visual-spatial perceptual problems, are common


Management of Turner syndrome

Tx with hormones to promote secondary sexual development
Surgical correction of congenital heart defects
Anticipatory guidance and early intervention to overcome learning disabilities
GH therapy for stature


Genetic counseling for Turner syndrome

Recurrence is rare