Common Genetic Disease

It is since two decade that there is an increasing awareness of the importance of genetic factors in the aetiology and pathogenesis of many disorders affecting man. Perhaps of most importance, is that this knowledge has also led the possible means of prevention of such disorders through genetic counselling and antenatal diagnosis.

Down's syndrome:

This occurs in about once in 700 live-births and is characterized by flat face with widely spaced and upward slanting eyes, epicanthic folds, brachycephaly, malformed ears broad and/or short neck and a single transverse palmer crease. Patients with Down's syndrome are invariably mentally retarded, but have a pleasant, quite personally and show a great fondness for music. About 1% of cases of Down's syndrome are mosaics, that is, they possess two different cell lines, one of which has a normal chromosome constitution, the other an extra chromosome 21. This arises as result of non-disjunction occurring at or after the first zygotic division and is very rarely inherited. The clinical picture may often be considerably modified in some of these cases.

Turner's syndrome: this was the first sex chromosome aneuploidy to be described in females. An XO sex chromosome constitution is the commonest abnormality and also arises by non-disjunction, but unlike Klinefelter's syndrome, Turner's syndrome does not show relationship with maternal age. Turner's syndrome may also result from isochromosomes, deletions and rings involving the X chromosome. The main clinical features of Klinefelter's Turner's syndrome are listed respectively, Sterility, small testes, Eunuchoid body proportions, Gynaeco mastia, Mental retardation and primary amenorrhoea, Sterility, Lack of secondary sexual characteristics, short stature and various congenital abnormalities.

Genetics of Haemophilia A: The factor VIII gene is localised on the X chromosome making haemophilia A, a sex linked disorder. Thus on pedigree grounds all daughters of haemophilia are obligate carriers and sisters have 50% chance of being a carrier. If a carrier has a son, he has 50% chance of haemophilia, and daughter has 50% chance of being a carrier. Haemophilia 'breeds true' within a family, as all members will have the same abnormality of a factor VIII gene, i.e. if one individual has severe haemophilia all other affected will also have a severe form of the disorder. Female carriers of haemophilia tend to have a reduced factor VIII levels because of random inactivation of the X chromosome in developing foetus. An indication of carrier ship can be ascertained by measurement of factor VIIIC: von Willebrand factor (vWF) ratio is reduced in carrier compared to normal individuals.

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