Genetic diseases are increasing due to factors like environmental pollution and improved diagnostic techniques. In China, it is estimated that 1 million new patients develop inherited disorders each year. Genetic diseases can be classified as chromosomal abnormalities, single gene disorders, and polygenic disorders. While most genetic diseases cannot be cured, treatment options include dietary restrictions, removing harmful substances, supplementing lacking substances, and gene therapy shows promise for some conditions. Prevention involves genetic counseling and prenatal testing.

1. Genetic Diseases (Inherited Diseases) Zou Xiao-bing Department of Pediatrics 3rd Affiliated Hospital Sun Yat-sen University

2. Great changes in medicine one of the biggest victories in medicine over the past 100 years is that infectious diseases have decreased dramatically, for example, smallpox was eradicated, poliomyelitis will soon be eradicated and pertusis , diphtheria , malaria , measles are diminishing

3. The reasons of the changes in medicine Social progress planned immunization Advances in medical sciences better nutrition

4. Genetic diseases are increasing

5. Reasons Environment pollution caused by development : mutagenic substances come from industrial wastes , nuclear wastes and modern human life, drug abuse such as the use of thalidomide . Improved diagnostic techniques include biochemical techniques, cytogenetic techniques and more important, molecular genetic techniques.

6. Epidemiology of genetic diseases in China It is estimated that ,each year in China , there are 20,000,000 live birth neonates. 5% of them will suffer from inherited disorders or birth defects. it means that each year there are 1,000,000 new patients. Over 10,000 kind of inherited diseases are found by now.

8. Basic of genetics Cell is the basic unit of human body . Chromosome is the carrier of inheritance and gene. Normal cell contain 23 pairs chromosomes , with about 30,000 structural genes

9. Basic of genetics chromosomes exist in pair, so genes exist in pair. Paired genes could be divided into dominant gene and recessive gene. traits are controlled by the genes One gene one enzyme theory the abnormal chromosomes and genes result in genetic diseases.

10. Classification of Genetic Diseases Chromosomal abnormalities: including euploid ,21 trisomy, 45,XO(turner syndrome) and structure abnormal such as 5P- and 14 ring. Gene diseases including single gene diseases such as PKU and polygenic diseases such as diabetes.

11. Classification of Genetic Diseases Chromosome diseases :quantity or structure of chromosome is abnormal autosomal chromosome diseases sex-linked chromosome diseases Gene diseases single gene inherited diseases (mendel model) polygenic inherited diseases :diabetes, asthma, congenital cardiac abnormalities, cleft lip, gastric ulcer, obesity, schizophrenia etc.

12. Classification of single gene inherited diseases Autosomal dominant inherited diseases brachydactyly 、  -thalassemia, marfan syndrome Autosomal recessive inherited diseases PKU 、 albinism X-linked dominant inherited diseases G-6PD deficiency, vit-D resistant rickets X-linked recessive inherited diseases hemophilia 、 Y-linked trait: hairy ear syndrome

13. Manifestation of genetic diseases Features in common:mental retardation 、 developmental delay, simian crease and abnormal dermatoglyphics , microcephaly and macrocephaly ,abnormal of genital organs,malformation of limb and extremities, spine and anal abnormal specific features:fair skin and unpleasant odor of PKU, White skin of albinsim, facial abnormalities of Down syndrome and thalassemia

14. Diagnosis approaches of genetic diseases Samples used blood amniotic fluid skin hair different kind of cells approaches chromosome analysis biochemical test Enzyme analysis gene analysis pedigree analysis dermatoglyphics

15. Treatment of Genetic Diseases Most genetic diseases couldn’t be cured. better care from family better welfare of the society function training gene therapy has show us a bright future, ADA(Adenosine Deaminase) deficiency, can be treated by gene therapy. (bone marrow transplantation and stem cell transplantation belong to gene therapy, ß- thalassemia can be treated by BMT)

16. Treatment of some single gene diseases Restrict specific food (Dietary restriction) : PKU-phenylalanine, G6PD deficiency-broad bean and aspirine Discharge harmful substances ( wilson disease-copper, thalassemia-iron); Supply lacking substances (hemophilia A- factor 8)

17. Prevention of genetic diseases Genetic counseling, marriage guidance and risk assessment find the carrier of the parents with abnormal gene prenatal diagnosis by amniocentesis and chorionic villous biopsy

18. DOWN SYNDROME First described by John Langdon Down in 1866, the syndrome is named after him. in 1956, Tijo found human cell contained 46 chromosomes. In 1959, Lejeune identified the underlying chromosomal abnormality of affected individuals having a additional #21 chromosome. It is the commonest chromosomal disease. Maternal age is linked to the syndrome.

19. Manifestation of Down Syndrome Facial abnormalities:small head,recessed nose, small ears and mouth mental retardation:IQ score less than 60 development delayed ,short statue , obesity, fingers are short and stubby, simian crease on the palm congenital heart disease and other malformations can be found in most cases.

21. Classification of Down Syndrome Trisomy 21 (account for 95% of the individuals). Translocation Down syndrome (4%) Mosaic Down syndrome (1%) translocation down syndrome don’t differ congnitively and medically from those with trisomy 21. but mosaic down syndrome is less severe because their trisomy cells are interspersed with normal cells.

22. Etiology of trisomy 21 Nondisjunction of chromosome #21 in meiosis

23. Etiology of translocation down syndrome During prophase of meiosis in a parent,there may be a transfer of a portion of one chromosome to another

24. Etiology of mosaic down syndrome death Develop to a mosaic down syndrome Nondisjunction of zygote during early stage

25. TURNER SYNDROME Karyotype of turner syndrome is 45 XO affected individuals are female in appearance , ovarian dysgenesis causing inferity, short stature, webbing of the neck, wildly spread nipples, cubitus valgus.

26. Klinefelter Syndrome Karyotype is 47,XXY the typical clinical features include male in appearance, inferity, gynaecomastia in adolessence, mental retardation, high and thin stature (usually over 180cm)

27. 47 XYY Syndrome Karyotype is 47 XYY The affected individuals are male in appearance, high and thin with increased tendency to be violent and so are more common in prison or to be a hero in wartime. END

28. Phenylketouria (PKU) Autosomal recessive disease inborn error of metabolism reason is the lack of phenylalanine hydroxylase or an essential co-factor(BH4) mental retardation and seizure dietary phenylalanine restriction in early infant is very important for mental development.

29. Clinical manifestations of PKU Mental retardation seizure, irritability abnormal EEG fair skin unpleasant odor of urine

30. Congenital hypothyroidism Result from deficient production of thyroid hormone. Clinical features include coarse facies,dry skin, hoarse cry, hypotonia, umblical hernia, constipation, prolonged jaundice, TSH↑ ， thyroxine↓ need life long supplement of thyroxine.

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32. 45, XO TURNER SYNDROME

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39. Mental retardation and autism-like symptom Long face and big ears

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