an account on sex chromosome disorders.

1. PRESENTED BY,
GOPIKA BEENA CHANDRAN
RGITBT, PUNE

2. Chromosomal abnormalities
• Chromosomal mutations are abnormal
changes in the number and structure of
chromosomes.
• Numerical changes are known as ploidy
changes.
• Ploidy changes bring about abnormal
alterations in the karyotype which causes
serious genetic disorders.

4. • Some of the genetic disorders caused by
ploidy changes and abnormal karyotypes are:
a) Autosomal anomalies
b) Sex chromosomal anomalies

6. Sex Chromosome Aneuploids:Female

7. • First reported by Henry Turner & his team in 1938.
• Also called ovarian dysgenesis.
• Abnormal female(sterile) condition (44A + X0).
• Caused by sex chromosomal monosomy, absence
of an X chromosome(XO Syndrome)
• The syndrome affects 1 in 2,500 female births.

8. • Can be caused in two ways:
a) Lack of Barr body.
b) Missing only part of an X chromosome or are
mosaics, with only some cells missing an X.

9.  At birth (looks normal) :
• puffy hands
• impaired lymph flow in feet
 In childhood:
• wide set nipples
• soft nails that turn up at the ends
• slight webbing at the back of the neck
• short stature
• coarse facial features
• low hairline at the back of head
• impaired hearing with frequent ear infection due
to defect in shape of coiled part of inner ear.

10.  At sexual Maturity :
• sparse body hair develops
• rudimentary / immature ovaries
• very small uterus, normal cervix and vagina
• Intelligence is normal.
• “Turner neurocognitive phenotype” may impair
the ability to solve math problems that entail
envisioning objects in three-dimensional
space.
• may cause memory deficits

11. • Offsprings of mosaics are at high risk of having
abnormal numbers of chromosomes.
• XO syndrome is unrelated to the age of the mother.
• Life span is shortened slightly.
• Adults more likely to develop other disorders like
osteoporosis, types 1 and 2 diabetes, and colon
cancer.

12. • many signs and symptoms of XO syndrome result from
the loss of specific genes:
eg:-a) loss of a gonadal dysgenesis gene accounts for
the ovarian failure
b) absence of a transcription factor causes short
stature.
c) Deletion of another gene causes the hearing
defect.

13. What can be done?
• Hormones (estrogen and progesterone) can be
given to stimulate development of secondary
sexual structures for individuals diagnosed
before puberty, and prompt use of growth
hormone can maximize height.

14. • Presence of an extra X chromosome. (3X)
• Occurs in about one in 1000 females.

15. Symptoms
• Tall stature
• Menstrual irregularities
• Rarely mentally retarded
• Tend to be less intelligent than their siblings

16. Sex Chromosome Aneuploids: Male

17. • Due to an extra X chromosome (47, XXY) caused by
chromosomal trisomy.
• First reported by Klinefelter in 1942.
• Results from non disjunction of chromosomes
during gametogenesis.
• Observed in About 1 in 500 males.
• Appear normal in childhood.
• Abnormalities seen in adults.
• Conditions such as 44A + XXYY, 44A + XXXY, 44A +
XXXYY, 44A + XXXXY are also observed.

18. Symptoms
• rudimentary testes and prostate glands
• sparse pubic and facial hair
• They have very long arms and legs, large hands and
feet
• may develop breast tissue( gynaecomastia)
• genetic or chromosomal cause of male infertility.
• Mental retardation in cases of more than 2 X
chromosomes.
• may be slow to learn

19. XXYY
• more severe behavioral problems
• tend to develop foot and leg ulcers, resulting from
poor venous circulation.
• childhood and adolescence include:
 attention deficit disorder
 obsessive compulsive disorder
 learning disabilities
• In the teen years:
 testosterone level is low
 development of secondary sexual characteristics
is delayed, and the testes are undescended
• infertile

20. What can be done?
• Testosterone injections during adolescence can limit
limb lengthening and stimulate development of
secondary sexual characteristics.
• Men with XXY syndrome have fathered children,
with medical assistance.
• Doctors select sperm that contain only one sex
chromosome and use the sperm to fertilize oocytes.

21. XYY Syndrome
• One male in 1,000 has an extra Y chromosome.
• Found by Jacobs et al in 1965, hence called Jacob’s
Syndrome.
• can arise from nondisjunction in the male,
producing a sperm with two Y chromosomes that
fertilizes an X-bearing oocyte.

22. Symptoms
• great height
• acne
• speech and reading problems
• Sterile
• Hypergonadism
• More aggressive than normal people.

23. • Previously called ‘X linked mental retardation’.
• In 1969 , a clue emerged to the genetic basis of X-
linked mental retardation.

24. • The tips at one chromosome end dangled,
separated from the rest of each chromatid by a thin
thread.

25. • When grown under specific culture conditions
(lacking folic acid), this part of the X chromosome
was very prone to breaking—hence, the name
‘fragile X syndrome’.
• affects 1 in 2,000 males and 1 in 4000 females.

26. Symptoms
• Youngsters look normal
• By young adulthood,
 faces are very long and narrow
 a long jaw
 protruding ears.
• The testicles are very large
• Mental impairment
• behavioral problems include mental retardation, learning
disabilities,repetitive speech, hyperactivity, shyness, social anxiety,
a short attention span, language delays, and temper outbursts.

27. INHERITANCE OF FRAGILE X SYNDROME

28. • inherited in an unusual pattern
• transmitted as any X-linked trait is, from carrier mother
to affected son.
• However, penetrance is incomplete.
• One-fifth of males who inherit the chromosomal
abnormality have no symptoms.
• As they pass on the affected chromosome to all their
daughters, are called “transmitting males.”
• A transmitting male’s grandchildren may inherit fragile
X syndrome.

29. How is it caused?
• A triplet repeat mutation.
• Normally, the fragile X area contains about 30
repeats of the sequence CGG, in a gene called
the fragile X mental retardation gene (FMR1).
• In people who have the fragile chromosome
and show its effects, this region is expanded
to 200 to 2,000 CGG repeats.

30. Contd.
• The FMR1 gene encodes fragile X mental
retardation protein (FMRP).
• This protein, when abnormal, binds to and disables
several different mRNA molecules whose encoded
proteins are crucial for brain neuron function.

31. • A distinct type of disorder has been described in the
maternal grandfathers of boys who have fragile X
syndrome.
• mothers of boys with fragile X syndrome reported the
same symptoms in their fathers—
• tremors, balance problems, and then cognitive or
psychiatric difficulties (inability to plan or pay attention,
and inappropriate behaviors).
• The grandfathers’ symptoms worsen with time and can
lead to premature death.

32. FXTAS
• New condition, called fragile X-associated tremor/ataxia
syndrome (FXTAS) developed.
• Ataxia is poor balance and coordination.
• develop tremors
• balance problems
• nervousness
• memory impairment.
• the symptoms of FXTAS arise from excess FMR1 mRNA,
which attracts and disables other mRNAs.

35. • rare, being estimated to occur in about
1/30,000 live births.
• if the translocated chromosome is lyonised (X
inactivation) , the genes on the translocated
autosome also get inactivated.
• Mechanism of inactivation is not clear.
• Unbalanced X; autosome translocation can
result in multiple congenital
abnormalities/mental retardation syndrome
due to chromosomal imbalance.