Seminar Genetic & Pediatric Diseases.pptx

Seminar of Genetic & Pediatric Diseases

1. Genetic & Pediatric Diseases Brijesh Kumar Rajwade Chhagan Lal Sonkar D Sunny Daneshwar Thakur Deepali Dhruw Deepti Arya Presented by Roll no. 34-39

2. The slide will cover Genetic Diseases Mutation Mendelian Disorders Structural Abnormalities of Chromosomes Numerical Abnormalities of Chromosomes Pediatric Diseases Tumours of Infancy & Childhood

3. Genetic Diseases Genetic disease is an inherited medical condition caused by gene abnormality. They disrupt the normal cellular homeostasis & produce a group of disease called disorders also known as Genetic disorders. There are many types of genetic abnormalities that affect the structure & function of proteins by translation process.

4. Classification of Human genetic disorders Disorders related to mutation Chromosomal disorders Complex multigenic disorders

5. Mutations The term mutation is applied to permanent change in the DNA of the cell. Mutations affecting germ cells are transmitted to the next progeny producing inherited disorders. Mutation affecting somatic cells give rise to various cancers & congenital malformations.

6. Types of Mutations Point Mutation Nonsense mutation Frameshift mutation Trinucleotide repeat mutation

7. Point Mutation Point Mutation is the result of substitution of a single nucleotide base by a different base i.e. replacement of an aminoacid by another. E.g. - In sickle cell anemia , there is a point mutation by substitution of glutamic acid by valine in the polypeptide chain.

8. Nonsense Mutation It is a type of mutation in which the protein chain is prematurely terminated. E.g.- In thalassemia , the synthesis of alpha or beta globin chain of hemoglobin is partially or totally stops.

9. Nonsense Mutation

10. Frameshift Mutation Frameshift mutation occurs when there is insertion or deletion of one or more base pairs in the DNA sequence. E.g. - O allele in ABO locus.

11. Frameshift Mutation

12. Trinucleotide repeat mutation Trinucleotide repeat mutation is characterised by amplification of a sequence of three nucleotides. Distinguishing feature is that they are dynamic i.e. the degree of amplification increases during gametogenesis. E.g.- Fragile X Syndrome

13. Mendelian Disorders They are the mutation involving single gene defects. They are of 3 types:- Autosomal Dominant Disorders Autosomal Recessive Disorders X-linked Recessive Disorders

14. Marfan Syndrome Marfan Syndrome is a disorder of connective tissues, manifested principally by changes in the skeleton, eyes & cardiovascular system. It results from an inherited defect in an extracellular glycoprotein called fibrillin-1. It's prevelance is estimated to be 1 in 5000.

15. Cystic Fibrosis (Mucoviscidosis) Cystic fibrosis is an inherited disorder of ion transport that affects fluid secretion in exocrine glands & in the epithelial lining of respiratory, gastrointestinal & reproductive tracts. The primary defect in cystic fibrosis is abnormal transport of chloride & bicarbonate ions mediated by Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene present on long arm(q) on chromosome 7.

16. Phenylketonuria :- It is an autosomal recessive disorder caused by a severe deficiency of enzyme phenylalanine hydroxylase (PAH) leading to hyperphenylalaninemia. The biochemical abnormality is an inability to convert phenylalanine into tyrosine. Galactosemia :- It is an autosomal recessive disorder of galactose metabolism in which there is lack of Galactose-1-uridyl transferase (GALT) enzyme . As a result galactose-1-phosphate accumulates in many locations like liver, spleen, kidney, lens of eye, cerebral cortex, heart muscle & erythrocytes.

17. Gaucher’s Disease This is an autosomal disorder in which there is mutation in lysozomal enzyme, acid β-glucosidase which normally cleavage glucose from ceremide. This results in lysosomal accumulation of sphingolipid glucosyl ceramide. Microscopy shows large no. of characteristically distended & enlarged macrophages called Gaucher cells. Clinical features:- Hepatomegaly, Splenomegaly, Lymphadenopathy, Pancytopenia & Thrombocytopenia.

18. Niemann-Pick Disease This is an autosomal recessive disorder characterised by accumulation of sphingomyelin & cholesterol due to defect in enzyme acid sphingomyelinase. Microscopy shows storage of sphingomyelin & cholesterol within lysosomes. The Niemann-Pick Cells are smaller than gaucher cells & their cytoplasm is foamy & vacuolated. Clinical features:- Hepatosplenomegaly, Lymphadenopathy, Loss of vision, Liver cirrhosis, Impaired lung function.

19. Fragile X Syndrome Fragile X Syndrome is the most common genetic cause of intellectual disability in males & overall the second most common cause after Down syndrome. It results from a trinucleotide expansion mutation in the familial mental retardation 1 (FMR1) gene .

20. Numerical Abnormalities Normal karyotype of a human nucleated somatic cell is diploid - 2N (46 chromosome) while the germ cell have haloid - 1N (23 chromosome). There are mainly 2 types of numerical abnormalities i.e. Polyploidy & Aneuploidy.

21. Polyploidy Polyploidy is the term used for no. of chromosomes which is a multiple of haploid no. i.e. triploid or 3N (69 chromosomes) or tetraploid or 4N (92 chromosomes). Polyploidy occurs normally in megakaryocytes & dividing liver cells.

22. Aneuploidy Aneuploidy is the no. of chromosomes which is not an exact multiple of haploid no. i.e. hypodiploid or 2N-1 (45 chromosomes) known as monosomy & hyperdiploid or 2N+1 (47 chromosomes) known as trisomy. Aneuploidy occurs due to non-disjunction i.e. failure of chromosomes to separate normally during cell division during first or second stage of meiosis or mitosis.

23. 3 Clinical Important Syndromes Down Syndrome Klinefelter Syndrome Turner Syndrome

24. Down Syndrome Down syndrome is the most common chromosomal disorder & occurs due to trisomy of 21st chromosome. Clinical features :- Mental retardation, flat face, enlarged & malformed ears, short & broad hands, congenital heart disease, enlarged colon, widely spaced big toes.

25. Klinefelter Syndrome It is a cytogenetic disorder involving sex chromosome. It is characterised by 2 or more X-chromosome (47, XXY) & occurs by trisomy of X-chromosome. Clinical features :- Hypogonadism, extragonadal germ cell tumours, testicular atropy, reduced spermatogenesis leads to infertility, tall height with long legs & gynaecomastia.

26. Turner Syndrome It is most common sex chromosome abnormality in females. It is characterised by loss of X-chromosome (45,XO) occurs by complete or partial monosomy of X-chromosome. Clinical features :- Short height with poorly developed breast, webbing of neck, underdeveloped ovaries, primary amenorrhea, cardiovascular anomalies- aortic constriction, brown spots & pigmented hair.

27. Other Syndromes Edward Syndrome - characterised by trisomy of 18th chromosome. Features are prominent occiput, intellectual disability, microganthia, low set ears, short neck, overlapping fingers and congenital heart defects, renal malformation, limited hip abduction & rocker-bottom feet. Patau Syndrome - characterised by trisomy of 13th chromosome. Features are micropthalmia, microcephaly, polydactyly, cleft lip & palate, umbilical hernia, rocker-bottom feet, cardiac & renal defects.

28. Pediatric Diseases Pediatric Diseases are the diseases affecting from birth to puberty. This period is conventionally subdivided into 4 stages:- Neonatal period :- Birth to first 4 weeks Infancy :- first year of life Early childhood :- 1-4 years Late childhood :- 5-14 years

29. Foetal Hydrops Foetal hydrops refers to oedema, fluid accumulation in the foetus during intrauterine growth. This of 2 types:- Immune hydrops :- Also called as Erythroblastosis Foetalis. It is due to Rh group incompatibility & infrequently ABO incompatibility. Non-immune hydrops :- It is due to cardiovascular defects, chromosomal anomalies & foetal anemia.

30. Sudden Infant Death Syndrome(SIDS) SIDS is unexplained death of infants (under 1yr) also known as crib death, usually during sleep. Although the cause is not known, a few risk factors have been associated with SIDS. Risk factors :- Brain defects, low birth weight, passive smoke in environment, recent respiratory infection, prematurity, inadequate perinatal care & family history of crib death.

31. Tumours of Infancy & Childhood Tumours of infancy & childhood comprise 2% of all malignant tumours but they are the leading cause of death of children usually 4-14 yrs exceeded only by accidents. It is sometimes difficult to seperate true tumours or neoplasms from tumour like lesions in the infant & children. It is of 2 types :- Benign & Malignant

32. Benign Tumours Benign tumours are more common than malignant tumours but they are generally of little immediate consequences. Many of the benign tumours seen in infancy & childhood are actually growth of displaced cells, masses of tissues & their proliferation takes place along with growth of child.

33. Malignant Tumours Malignant tumours are the major cause of death in children. They are different from benign tumours in incidence, frequency, prevelance, tendency & survival. E.g.- Acute leukaemia, Blastoma (neuroblastoma, hepatoblastoma, retinoblastoma, nephroblastoma)

34. References ROBBINS & COTRAN PATHOLOGIC BASIS OF DISEASE, 10th edition, Volume I Textbook of PATHOLOGY Harsh Mohan, 8th edition

35. Thank you!