UNIT IX: GENETIC DISORDERS

Transcription

1 UNIT IX: GENETIC DISORDERS Younas Masih Lecturer New Life College Of Nursing Karachi 3/4/2016 1

2 Objectives By the end of this session the Learners will be able to, 1. Know the basic terms related genetics 2. Discuss chromosomes. 3. Understand the Patho-physiology and clinical manifestations of the diseases like, 4. Down's Syndrome 5. Turner's syndrome 6. Klienfelter s Syndrome 3/4/2016 2

3 Terminology Genes Genes are the basic unit of genetics. Human have only genes in the body These genes account for only about 3 per cent of our DNA. The function of the remaining 97 per cent is still not clear Genes are made of a chemical called DNA 3/4/2016 3

4 Terminology Chromosomes DNA molecules are tightly packed around proteins called histones to make structures called chromosomes. Human beings have 23 pairs of chromosomes in every cell, which makes 46 chromosomes in total. A photograph of a person's chromosomes, arranged according to size, is called a karyotype. The sex chromosomes determine whether you are a boy (XY) or a girl (XX). The other chromosomes are called autosomes. 3/4/2016 4

5 Types of chromosomes 3/4/2016 5

6 Terminology 3/4/2016 6

7 Terminology The largest chromosome, chromosome 1, contains about 8000 genes. The smallest chromosome, chromosome 21, contains about 300 genes. DNA 'deoxyribonucleic acid'. The DNA molecule is a double helix: that is, two long, thin strands twisted around each other like a spiral staircase. 3/4/2016 7

8 Terminology Alleles The genes on each chromosome are arranged in pairs The two members of a gene pair one inherited from the mother and the other from the father, are called alleles. If the members of a gene pair are identical the person is homozygous If the two members are different, the person is heterozygous. 3/4/2016 8

9 Terminology Genotype The genetic information stored in the code The genetic composition of a person is called a genotype Phenotype The physical traits associated with a specific genotype. Phenotype is the observable expression of a genotype in terms of morphologic, biochemical, or molecular traits 3/4/2016 9

10 Terminology If the trait is expressed in the heterozygote it is said to be dominant If it is expressed only in the homozygote, it is recessive A gene mutation is a biochemical event such as nucleotide change, deletion, or insertion that produces a new allele 3/4/

11 Terminology Monosomy: The condition of having a diploid chromosome complement in which one (usually the X) chromosome lacks its homologous partner. Chromosomal abnormality consisting of the absence of one chromosome from the normal diploid number. 3/4/

12 Terminology Trisomy: A condition in which an extra copy of a chromosome is present in the cell nuclei, causing developmental abnormalities. Chrosomal abnormality in which there is one more than the normal number of chromosomes in a cel 3/4/

13 Terminology Polysomy: Congenital defect of having one or more extra chromosomes in somatic cells. Polysomy is a condition in which an organism has at least one more chromosome than normal, i.e. the number of a particular chromosome is not diploid - there may be three or more copies of the chromosome rather than the expected two copies. 3/4/

14 Down syndrome First described in 1866 by John Langon Down Diagnosis was made clinically until 1959 Trisomy 21, or Down syndrome Down syndrome is one of the first symptom complexes associated with mental retardation to be identified as a syndrome. 3/4/

15 3/4/

16 Down s Syndrome All persons with Down syndrome have duplicated chromosome 21 material The origin of the duplicated genetic material can vary Nondisjunction (about 96% of cases) The extra chromosome may arise by abnormal sorting(during meiosis cell division) to produce an extra, free-standing chromosome (trisomy 21). 3/4/

17 Down s syndrome Translocation (3 % of cases) A joining of chromosomes to produce extra chromosome 21 material that is attached to another chromosome In which part of chromosome 21 breaks off and attaches to another chromosome (usually chromosome 14). Mosaicism (1-2%) Is a condition in which cells within the same person have a different genetic makeup. Patients with mixtures of normal and trisomic cells (mosaic Down syndrome) often have milder phenotypes. Percentages of normal cells within the blood sample used for chromosome studies may differ from the percentages of normal cells in other tissues like brain or heart. 3/4/

18 Causes Increased maternal age Drugs Chemicals Radiation 3/4/

19 Clinical features Small, square head. There is upward slanting of the eyes Malformed ears A fat pad at the back of the neck An open mouth Large, protruding tongue The child s hands usually are short and stubby Epicanthal folds (folds around the corner of the eye) 3/4/

20 Clinical features Only a single palmar (i.e., simian) crease Hypotonia Congenital heart defects Increased risk for gastrointestinal malformations. Chances of acute leukemia Alzheimer s disease among older persons 3/4/

21 Turner s Syndrome It is first time described by Henry Turner in Complete or partial Monosomy of X chromosome Hypogonadism Phenotypic female 45,X The disorder affects approximately 1 of every 2500 live births It has been estimated that more than 99% of fetuses are spontaneously aborted in the first trimester 3/4/

22 Turner syndrome Turner syndrome is caused by a missing or incomplete X chromosome. People who have Turner syndrome develop as females. Some of the genes on the X chromosome are involved in growth and sexual development, which is why girls with the disorder are shorter than normal and have incompletely developed sexual characteristics. 3/4/

23 Turner syndrome 3/4/

24 Clinical features Short in stature(rarely exceeding 125cm in height), but her body proportions are normal She does not menstruate and shows no signs of secondary sex characteristics Variations in the syndrome range from essentially none to webbing of the neck with redundant skin folds and low hairline. Non pitting lymphedema of the hands and feet, Congenital heart defects particularly coarctation of the aorta & bicuspid aortic valve 3/4/

25 Clinical features Turner syndrome usually does not affect intelligence. Arms that turn out slightly at the elbow 3/4/

26 klinefelter syndrome 3/4/

27 klinefelter syndrome The term Klinefelter syndrome describes a group of chromosomal disorder in which there is at least one extra X chromosome added to a normal male karyotype, 46,XY. It occurs in about 150 per 100,000 males and is the most frequent chromosomal aberration in males. Male has extra Chromosome Known as XXY male Male has total of 47 chromosomes 3/4/

28 Characteristics These boys are similar to other boys, phenotypically no difference from others Small testicular size is the only consistent physical feature in 47,XXY. Gynecomastia Sparse body hair 3/4/

29 Characteristics Growth/Stature Infants and children have normal heights, weights, and head circumferences. The increase in height is most significant between ages 5 and 8 and results in the mean final height of cm. Affected individuals have longer arms and legs 3/4/

30 Characteristics Fertility Although most patients with Klinefelter syndrome are infertile, there have been a few patients with reports of pregnancy without assisted medical technology, 3/4/

31 Psychological characteristics Intelligence A wide range of intelligence quotient (IQ) has been noted and extends from well below average to well above average. Based on the Wechsler Intelligence Test, Verbal IQ is usually lower than Performance IQ(intelligence quotient) Language development Several longitudinal studies of males with 47,XXY have revealed a tendency for language deficits that often causes academic difficulties during the school years. 3/4/

32 3/4/

33 Behavior and personality The personalities of 47,XXY males are variable. One study characterized 47,XXY males as timid, immature, and reserved, with difficulty relating to their peer group, Whereas other studies described 47,XXY subjects as friendly, kind, helpful, and relates well with other people. Most are described to be quiet, sensitive, and unassertive. 3/4/

34 Etiology The extra X chromosome in 47,XXY results sporadically from either meiotic non disjunction where a chromosome fails to separate during the first or second division of gametogenesis or from mitotic non disjunction in the developing zygote. The likelihood of X chromosome non disjunction increases with advancing maternal age. 3/4/

35 Physical features Small testes Infertility Gynecomastia Long legs and arms Developmental delay Speech and language deficits 3/4/

36 Congenital Abnormalities Congenital abnormalities are usually considered as those that have developed in the absence of a genetic or chromosomal cause, and occur when the baby has developed an abnormality in the womb often for no apparent reason. These abnormalities include hare lip, cleft palate, heart defects, spina bifida, absent limbs or extra digits. Most of these abnormalities are detectable on ultrasound at weeks. 3/4/

37 Examples of Congenital abnormalities 3/4/

38 Congenital Abnormalities Severe congenital abnormalities such as major heart and central nervous system (brain and spinal cord) malformations often result in miscarriage or death of the baby before 24 weeks; these defects can almost always be picked up with ultrasound screening 3/4/

39 Genetic abnormalities Those that occur usually because of a defective gene (length of DNA portion containing a genetic blueprint) that you or your partner are carrying, but not necessarily suffering ill effects from, therefore may not know that you possess. Chromosomal abnormalities include Down s syndrome (trisomy 21; trisomy means three chromosomes instead of two) and rarer, usually lethal syndromes. A chromosome is a ''bundle'' of genetic material, and the normal number contained in cells in our bodies is 46 (22 pairs=44, plus two sex chromosomes X and Y; XX=female, XY=male). In Down's syndrome, which occurs more frequently in older mothers, an extra chromosome 21 is present which can give rise to congenital abnormalities and learning difficulties later on. An absence of a sex chromosome may cause Turner's syndrome (45XO); 3/4/

40 References /chromosomal/turner/ c/highereducation/topics/dnageneschromosome s /questions/qu_272-what-is-the-differencebetween-chromosomal-genetic-and-congenitalabnormalities.html Porth, M. C. (2009). Pathophysiology Concepts of altered health states (7 th ed.). Lippincott Williams & Wilkins. Acknowledgment to sir Shahzad Bashir 3/4/