Sex chromosome disorders

an account on sex chromosome disorders.

1. DISORDERS OF SEX CHROMOSOMES 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.

3. Some of the genetic disorders caused by ploidy changes and abnormal karyotypes are: Autosomal anomalies Sex chromosomal anomalies

4. Sex Chromosome Aneuploids:Female

5. 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. Turner’s Syndrome

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

7. 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.

8. 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

9. 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 .

10. 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.

11. 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.

12. Presence of an extra X chromosome. (3X) Occurs in about one in 1000 females. TRIPLO-X

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

14. Sex Chromosome Aneuploids : Male

15. 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. Klinefelter’s Syndrome

16. 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

17. 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

18. 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 .

19. 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 .

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

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

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

23. 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.

24. 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.

25. INHERITANCE OF FRAGILE X SYNDROME

26. 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.

27. 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 .

28. 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.

29. 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.

30. 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.

31. X autosome translocations 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.