Human Genome 2023.pptx dr hussein e abass

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1. Human Genome Spinal Muscular Atrophy Trisomy 21 Dr Hussein Abass Consultant of Pediatrics September 2023

2. Human Cell

3. There are about 37.2 Trillion Human Cells in the adult human body, varying from about 20 to 40 trillion depending on the sex, age and weight, and a roughly equal number of bacterial cells. The human cells have been categorized into about 300 Cell Types based on location and function within the body .

4. Human Chromosomes

5. Chromosomes vary in number and shape among living organisms. Most bacteria have one or two circular chromosomes. Humans, along with other animals and plants, have linear chromosomes . In fact, each species of plants and animals has a set number of chromosomes. A fruit fly, for example, has four pairs of chromosomes, while a rice plant has 12 and a dog, 39. In humans, the twenty-third pair is the sex chromosomes, while the first 22 pairs are called autosomes. Typically, biologically female individuals have two X chromosomes (XX) while those who are biologically male have one X and one Y chromosome (XY). However, there are exceptions to these rules. Chromosomes are also different sizes. The human X chromosome is about three times larger than the human Y chromosome, containing about 900 genes, while the Y chromosome has about 55 genes. The unique structure of chromosomes keeps DNA tightly wound around spool-like proteins, called histones. Without such packaging, DNA molecules would be too long to fit inside cells! For example, if all of the DNA molecules in a single human cell were unwound from their histones and placed end-to-end, they would stretch 6 feet.

6. James Watson and Francis Crick has made a major contribution in 1953 to the development of the structure of DNA. The Nobel Prize in Physiology or Medicine in 1962 was awarded to James Watson, Francis Crick and Maurice Wilkins for their discovery of the molecular structure of DNA, which helped solve one of the most important of all biological riddles.

7. DNA is the information molecule for all living organisms. All of the DNA of an organism is called its genome. Some genomes are incredibly small, such as those found in viruses and bacteria, whereas other genomes can be almost unexplainably large, such as found in some plants. It is still quite puzzling why there does not appear to be a consistent correlation between biological complexity and genome size. For example, the human genome contains about 3 billion nucleotides . While 3 billion is a big number, the rare Japanese flower called Paris japonica has a genome size of roughly 150 billion nucleotides , making it 50 times the size of the human genome. To date, humans are the only life form that has successfully sequenced its own genome, yet there are many life forms on earth that have genomes substantially larger from the human genome.

8. Each cell contains 6 pg of DNA , so the total amount of DNA in the body is: Total DNA = 35 trillion cells × 6 pg /cell = 210 trillion pg To convert picograms to kilograms, we divide by 10^12 (one trillion): Total DNA mass = 210 trillion pg ÷ 10^12 pg /kg = 0.21 kg .

9. DNA

10. The applications of Genetic Engineering have brought about great progress in the field of health care in terms of accurate diagnosis of diseases, as well as in the therapeutic aspect and production of pharmaceutical products, which has led to the emergence of new medical sciences, including gene therapy and the science of using genomes in the pharmaceutical industries (genomic pharmacy). pharmacogenomics , as well as Public Health Genomics . Gene Therapy is the process of introducing healthy genes into cells to correct the functioning of ineffective genes in order to treat the disease. The idea is based on introducing a functionally effective gene into the cells by uploading the genes to a medium known as a carrier. The vector then infects the target cells and introduces the gene into the cell, thus reproducing the missing protein. Target cells can be transfected either by extracting the cells, culturing them, transfecting them ex vivo and then re-implanting them into the patient, or directly in vivo. As for the science of using genomics in the pharmaceutical industry (pharmaceutical genomics), it is one of the branches of pharmaceutical science that deals with the effect of genetic diversity on the response to drugs in patients by linking gene expression with the effectiveness or toxicity of the drug.

11. Gene Therapy has shown promising results in the treatment of human diseases, including Tumors , Autoimmune disorders , and infectious diseases . Normally, gene therapy is generated by transferring specific genetic information into target cells to alter their functions in disease therapy. In particular, gene therapy can be used for replacing or blocking mutated genes that cause diseases. Moreover, recent reports have demonstrated that gene therapy can also be used for inserting target genes against diseases. Meanwhile, many studies have indicated that vectors play a significant role in delivering genes. Different types of delivery vectors have been designed in the past few years of studies. Among them, several kinds of virus-based vectors, such as retroviral vectors, lentiviral vectors, adenoviral vectors, as well as adeno-associated viral vectors , are widely used in gene therapy development. Besides, many advanced technologies, such as genetic engineering, recombinant DNA technique, as well as mRNA technology, have been utilized in improving the performance of gene therapy in disease treatments.

12. The Genome is the entire set of DNA instructions found in a cell. In humans, the genome consists of 23 pairs of chromosomes located in the cell’s nucleus, as well as a small chromosome in the cell’s mitochondria. A genome contains all the information needed for an individual to develop and function.

13. 1- Number of Human Being in 2023 = 8.1 Billion People 2- Number of Human Cells = 37.2 Trillion Cells 3- Number of Human Genes = 20,000 – 25,000 Gene 4- Number of Human Diseases = about 100,000 Disease 5- There are over 6,000 known genetic disorders in humans.

14. Classifications of Diseases : The most widely used classifications of disease are Topographic, by bodily region or system Anatomic, by organ or tissue Physiological, by function or effect Pathological, by the nature of the disease process Etiologic (causal) Juristic, by speed of advent of death Epidemiological Statistical. Any single disease may fall within several of these classifications.

15. The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional • formally begun in October 1990 and completed in 2003 . • to discover all the estimated 20,000 to 25,000 human genes and make them accessible for further biological study. Time line of Human Genome Project 1970 Fredrick Sanger developed a technique for DNA sequencing, known as the Sanger’s method of DNA sequencing 1985 Robert Sinsheimer at UCSC proposed the idea of sequencing the human genome. 1986 The U.S. Dept of Energy and the National Institute of Health came forward to fund the Human Genome Project. The Human Genome Project took 13 years and thousands of researchers. The final cost: $3.0 billions.

16. Benefits of Human Genome Project Research : - A- Benefits of HGP Research Medical Benefits - improved diagnosis of disease - earlier detection of predispositions to disease - rational drug design - gene therapy and control systems for drugs - pharmacogenomics “personal drugs” - organ replacement - B- Benefits of HGP Research Microbial Genome Research - new energy sources (biofuels) - environmental monitoring to detect pollutants - protection from biological and chemical warfare - safe, efficient toxic waste cleanup

17. - C- Benefits of HGP Research DNA Forensics - identify potential suspects at crime scenes - exonerate wrongly accused persons - identify crime and catastrophe victims - establish paternity and other family relations - identify endangered and protected species as an aid to wildlife officials (prosecution of poachers) - detect bacteria and other organisms that may pollute air, water, soil, and food - match organ donors with recipients in transplant programs - determine pedigree for seed or livestock breeds - authenicate consumables such as caviar and wine - D- Benefits of HGP Research Agriculture and Livestock - disease-, insect-, and drought-resistant crops - healthier, more productive, disease-resistant farm animals - more nutritious produce - biopesticides - edible vaccines incorporated into food products - new enviornmental cleanup uses for plants like tobacco

18. - E- Benefits of HGP Research Evolution and Human Migration - use germline mutations in lineages to study evolution - study migration of different population groups based on female genetic inheritance - study mutations on the evolutionarily stable Y chromosome to trace lineage and migration - compare breakpoints in the evolution of mutations with ages of populations and historical events - F- Benefits of HGP Research Risk Assessment - assess health damage and risks caused by radiation exposure, including low-dose exposures - assess health damage and risks caused by exposure to mutagenic chemicals and cancer-causing toxins - reduce the likelihood of heritable mutations

19. Human Genome : Made up of DNA, which has four different chemical building blocks: DNA from all organisms is made up of the same chemical and physical components. The DNA sequence (3 billion bases) is the particular side- by-side arrangement of bases along DNA strand (e.g. ATTCCGGA) for each unique individual. These are called bases that and are abbreviated A, T, C, and G. Form the rungs of the double-helix model. Estimates of 20-25,000 genes in the human genome. The human genome is arranged into 24 distinct chromosomes (range from 50-250 million base pairs each). To put into perspective:  To get an idea of the size of the human genome present in each of our cells, consider the following analogy: If the DNA sequence of the human genome were compiled in books, the equivalent of 200 volumes the size of a Manhattan telephone book (at 1000 pages each). This would take about 9.5 yrs to read out loud at a rate of 10 bases per second. This would also take up 3 gigabytes of computer data storage space to store the entire nucleotide sequence of the human genome.

20. The Human Genome Project (HGP) was formally started in October 1990 and was expected to run for 15 years, but was finished early after 13 years in 2003. The Department of Energy's Human Genome Program and the National Institutes of Health's National Human Genome Research Institute (NHGRI) together sponsored the U.S. Human Genome Project. It is an international effort: Some 18 countries have participated in the worldwide effort, with significant contributions from the Sanger Center in the United Kingdom and research centers in Germany, France, and Japan. They allocated money to many laboratories across the U.S. to complete the research.

21. Overall Goals of HGP: To determine the complete sequence of the 3 billion chemical base pairs that make up DNA. Identify all human genes: Approximately 20,000-25,000 genes in human DNA Determine the sequences of the 3 billion chemical base pairs that make up human DNA Store this information in databases Improve tools for data analysis Make them accessible for further biological study. Address the ethical, legal, and social issues (ELSI) that may arise from the project.Transfer related technologies to the private sector Relate studies involving parallel sequencing of other “model” organisms to help develop the technology and interpret human gene function. Called Comparative Genomics Has included humans, rats, mice, fruit flies, and E. coli and other types of bacteria.

22. James Watson and Francis Crick has made a major contribution in 1953 to the development of the structure of DNA. They combined the physical and chemical data and proposed DNA as double helical twisted molecules connected together by hydrogen bonds. DNA is a backbone for all life and this model has helped to unlock the genetic code of all living organisms. It has also made to believe that the genetic pieces of information are held inside the structure and makes a new copy of the entire molecule and transfers it in a series of a generation.

23. DNA molecules are composed of a sequence of four nucleotide monomers namely Adenine (A), Cytosine (C), Thymine (T), and Guanine (G). - Nitrogen bases - Deoxyribose sugar - A phosphate group 1. Nitrogen bases Nitrogen-containing base functions in bonding nucleic acids and are also termed nucleobases due to their role in nucleic acid. DNA is composed of two major nitrogen bases: Purine and Pyrimidine. Two nucleotides of purine are Adenine (A) and Guanine (G) and pyrimidine are Cytosine (C) and Thymine (T). Two bases of a nucleotide pair each other with a hydrogen bond and forms two strands of double helix structure. Hydrogen atoms of amino groups act as a donor while carbonyl oxygen and ring nitrogen act as an acceptor. Adenine always pairs up with Thymine by two hydrogen bonds (A=T) similarly, Guanine pairs up with Cytosine forming triple hydrogen bonds (G≡C). Chargaff’s rule states that purine and pyrimidine bases should have a 1:1 stoichiometric ratio i.e , the amount of adenine must be equal to the amount of thymine and that similar to guanine and cytosine. The helix contains ten nucleotides in each turn with an internucleotide distance of 3.4A° whereas full turn helix length is 34A° with 20A° diameter.

24. This helical turning forms two grooves: Major grooves and minor grooves. The major groove appears deep and wide and is the specific binding site of proteins while the minor groove is the distance between two strands. 2. Deoxyribose sugar Deoxyribose sugar is a five-carbon atom sugar molecules that lack one hydroxyl group on the 2’ carbon i.e , one oxygen molecule is absent thus its name deoxyribose sugar. It is a cyclic molecule with five carbon atoms, among which four are carbon molecules and one oxygen molecules which are arranged in a cyclic manner. Due to its flexible structure, it can be twisted into various conformations like in canonical B-DNA, the sugar configuration is C2’ endo. The deoxyribose sugar molecule for all nucleobase is the same. When a nucleobase is attached to a deoxyribose sugar it becomes a nucleoside. The 1’ carbon of the pentose sugar bonds with the nitrogenous base and the 5’ end carbon atom bonds to the phosphate group. Then, the phosphate group bonds to the 5’ end of the nucleotide. All these bonding are followed by hydrogen carbon. During replication, several enzymes are involved in the breakdown of hydrogen bonding which later forms a newly stranded DNA molecule.

25. These newly formed ribose molecules attach with nitrogenous bases and a phosphate group before being deoxygenated and later become deoxyribose and become an independent DNA molecule. 3. A phosphate group A phosphate group is a backbone for every single strand of the DNA molecule. The chemical structure of the phosphate group comprises a functional group with a phosphorous atom bonded with four oxygen atoms in which 3 are singly bonded and one with a double bond. The phosphate group remains exterior of the DNA and are attached to the 5’ of each sugar atom and forms phosphodiester bond. The phosphate group functions as an energy donor when DNA synthesizes. Phosphate groups when attaches to the nucleoside form nucleotide molecules.

26. Types of Genetic Testing : Diagnostic testing . If you have symptoms of a disease that may be caused by genetic changes, sometimes called mutated genes, genetic testing can reveal if you have the suspected disorder. For example, genetic testing may be used to confirm a diagnosis of cystic fibrosis or Huntington's disease. Presymptomatic and predictive testing . If you have a family history of a genetic condition, getting genetic testing before you have symptoms may show if you're at risk of developing that condition. For example, this type of test may be useful for identifying your risk of certain types of colorectal cancer. Carrier testing . If you have a family history of a genetic disorder — such as sickle cell anemia or cystic fibrosis — or you're in an ethnic group that has a high risk of a specific genetic disorder, you may choose to have genetic testing before having children. An expanded carrier screening test can detect genes associated with a wide variety of genetic diseases and mutations and can identify if you and your partner are carriers for the same conditions. Pharmacogenetics . If you have a particular health condition or disease, this type of genetic testing may help determine what medication and dosage will be most effective and beneficial for you. Prenatal testing . If you're pregnant, tests can detect some types of abnormalities in your baby's genes. Down syndrome and trisomy 18 syndrome are two genetic disorders that are often screened for as part of prenatal genetic testing. Traditionally this is done looking at markers in blood or by invasive testing such as amniocentesis. Newer testing called cell-free DNA testing looks at a baby's DNA via a blood test done on the mother. Newborn screening . This is the most common type of genetic testing. In the United States, all states require that newborns be tested for certain genetic and metabolic abnormalities that cause specific conditions. This type of genetic testing is important because if results show there's a disorder such as congenital hypothyroidism, sickle cell disease or phenylketonuria (PKU), care and treatment can begin right away. Preimplantation testing . Also called preimplantation genetic diagnosis, this test may be used when you attempt to conceive a child through in vitro fertilization. The embryos are screened for genetic abnormalities. Embryos without abnormalities are implanted in the uterus in hopes of achieving pregnancy

27. Genome Sequencing When genetic testing doesn't lead to a diagnosis but a genetic cause is still suspected, some facilities offer genome sequencing — a process for analyzing a sample of DNA taken from your blood. Everyone has a unique genome, made up of the DNA in all of a person's genes. This complex testing can help identify genetic variants that may relate to your health. This testing is usually limited to just looking at the protein-encoding parts of DNA called the exome.

28. Types of Genetic Tests 1-Single gene testing . Single gene tests look for changes in only one gene. Single gene testing is done when your doctor believes you or your child have symptoms of a specific condition or syndrome. Some examples of this are Duchene muscular dystrophy or sickle cell disease. Single gene testing is also used when there is a known genetic mutation in a family. 2-Panel testing . A panel genetic test looks for changes in many genes in one test. Genetic testing panels are usually grouped in categories based on different kinds of medical concerns. Some examples of genetic panel tests are low muscle tone, short stature, or epilepsy. Panel genetic tests can also be grouped into genes that are all associated with higher risk of developing certain kinds of cancer, like breast or colorectal (colon) cancer. 3-Exome sequencing looks at all the genes in the DNA (whole exome) or just the genes that are related to medical conditions (clinical exome). 4-Genome sequencing is the largest genetic test and looks at all of a person’s DNA, not just the genes. 5-Testing for changes other than gene changes : --Chromosomes. DNA is packaged into structures called chromosomes. Some tests look for changes in chromosomes rather than gene changes. Examples of these tests are karyotype and chromosomal microarrays. -- Gene expression . Genes are expressed, or turned on, at different levels in different types of cells. Gene expression tests compare these levels between normal cells and diseased cells because knowing about the difference can provide important information for treating the disease. For example, these tests can be used to guide chemotherapy treatment for breast cancer.

29. Sampling for Genetic Tests : Blood sample . A member of your health care team takes the sample by inserting a needle into a vein in your arm. For newborn screening tests, a blood sample is taken by pricking your baby's heel. Cheek swab . For some tests, a swab sample from the inside of your cheek is collected for genetic testing. Amniocentesis . In this prenatal genetic test, your doctor inserts a thin, hollow needle through your abdominal wall and into your uterus to collect a small amount of amniotic fluid for testing. Chorionic villus sampling . For this prenatal genetic test, your doctor takes a tissue sample from the placenta. Depending on your situation, the sample may be taken with a tube (catheter) through your cervix or through your abdominal wall and uterus using a thin needle.

30. Types of Karyotying : 1. Banding 2. Fluorescence in Situ Hybridization (FISH) 3. Comparative Genomic Hybridization (CGH)

31. Types of Genetic Test Results Positive – the test found a genetic change known to cause disease. Negative – the test did not find a genetic change known to cause disease. Sometimes a negative result occurs when the wrong test was ordered or there isn’t a genetic cause for that person’s symptoms. A “true negative” is when there is a known genetic change in the family and the person tested did not inherit it. If your test results are negative and there is no known genetic change in your family, a negative test result may not give you a definite answer. This is because you might not have been tested for the genetic change that runs in your family. Uncertain – a variant of unknown or uncertain significance means there isn’t enough information about that genetic change to determine whether it is benign (normal) or pathogenic (disease causing). A good way to think about genetic testing is as if you’re asking the DNA a question. Sometimes we don’t find an answer because we weren’t asking the right question or science just didn’t have the answer yet.

32. مرض ضمور العضلات الشوكى Spinal Muscular Atrophy SMA

33. أعلن الرئيس عبد الفتاح السيسي يوم الأربعاء 30/6/2021 أن الدولة المصرية ستتحمل تكلفة علاج الأطفال المصابين مرض الضمور العضلي بالدواء الجديد Zolgensma من شركة نوفارتس السويسرية والتي تبلغ ثمن الجرعة الواحدة منه 2 مليون دولار لكل طفل. ومن الجدير بالذكر أن مصر بها 204 حالات مصابة بهذا المرض ، بينها 57 حالة لأطفال تحت سن عامين ، وهم الأكثر حظا ولهم فرصة أكبر للشفاء من هذا المرض. وعلى هذا تم تشكيل لجنة فرعية تأمين صحى بكل محافظة لفحص وتشخيص وتقييم الحالات وعمل التحاليل اللازمة ( رسم عضلات ثم تحليل جينات لتحديد الجين المعيب ) وتحديد الحالات المطابقة لمعايير إعطاء هذا الدواء وسيبدأ علاج الحالات حتى سن سنتين والتى لا تحتاج لمساعدة تنفسية ثم تقوم هذه اللجان الفرعية برفع تقريرها للجنة العليا بوزارة الصحة لبحث الحالة ومدى إستحقاقها وإنطباق المعايير عليها وتقوم بتوفير الآليه التى يتم بها توفير الدواء بالتعاون من صندوق تحيا مصر وتم تخصيص ثلاثة مراكز لتلقي العلاج هي مستشفى معهد ناصر ومستشفى الجلاء العسكري ومستشفى عين شمس الجامعي . ومرفق هنا جدول بعناوين ومواعيد العيادات المتخصصة لفحص مرضى ضمور العضلات الشوكى بعد التسجيل فى الهوت لاين على الرقم 106 .

34. الحجز على الخط الساخن رقم 106

35. Spinal Muscular Atrophy (SMA) is an inherited neuromuscular disorder characterized by progressive skeletal muscle hypotonia affecting voluntary movements. A recessive mutation in the survival motor neuron 1 (SMN1) gene, which is required for proper production of the SMN protein, leads to irreversible loss of α motor neurons in the ventral spinal cord and motor nuclei in the lower brainstem. Symmetric, proximal greater than distal, and progressive muscle weakness is the hallmark symptom. SMA is the second most common autosomal recessive disorder worldwide and the most common cause of infant mortality, with an estimated incidence of 1 in 10,000 live births and estimated prevalence of 1 to 2 per 100,000 persons .Approximately 2% of SMA cases are de novo mutations.

36. The pathogenesis of SMA centers around a mutation in the SMN1 gene that causes the absence of exon 7, which encodes 90% of the genetic material for the SMN protein. The other 10% of genetic material is encoded by the survival motor neuron 2 (SMN2) gene. SMN2 and SMN1 share 99% of nucleotide identity, except that SMN2 does not transcribe exon 7. However, the SMN2 gene copy number is the most important modifier for SMA disease severity. If an individual has a higher number of SMN2 copies in the absence of SMN1, the prognosis may be better.5 SMA is classified by types 0 to 4 with lower numbers reflecting greater clinical severity .

37. Proximal spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an early-onset, autosomal recessive neurodegenerative disease characterized by the loss of spinal α-motor neurons. This loss of α-motor neurons is associated with muscle weakness and atrophy. SMA can be classified into five clinical grades based on age of onset and severity of the disease. Regardless of clinical grade, proximal SMA results from the loss or mutation of SMN1 (survival motor neuron 1) on chromosome 5q13. In humans a large tandem chromosomal duplication has lead to a second copy of the SMN gene locus known as SMN2. SMN2 is distinguishable from SMN1 by a single nucleotide difference that disrupts an exonic splice enhancer in exon 7. As a result, most of SMN2 mRNAs lack exon 7 (SMNΔ7) and produce a protein that is both unstable and less than fully functional. Although only 10–20% of the SMN2 gene product is fully functional, increased genomic copies of SMN2 inversely correlates with disease severity among individuals with SMA. Because SMN2 copy number influences disease severity in SMA, there is prognostic value in accurate measurement of SMN2 copy number from patients being evaluated for SMA. This prognostic value is especially important given that SMN2 copy number is now being used as an inclusion criterion for SMA clinical trials. In addition to SMA, copy number variations (CNVs) in the SMN genes can affect the clinical severity of other neurological disorders including amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). This review will discuss how SMN1 and SMN2 CNVs are detected and why accurate measurement of SMN1 and SMN2 copy numbers is relevant for SMA and other neurodegenerative diseases.

38. Degeneration of alfa motor neurons

39. Lower Motor Neurone Somatic Motor Neurons Located in the brainstem and further divide into three categories: alpha, beta, and gamma. 1-Alpha motor neurons innervate extrafusal muscle fibers and are the primary means of skeletal muscle contraction. The large alpha motor neuron cell body can be either in the brainstem or spinal cord. In the spinal cord, the cell bodies are found in the anterior horn and thus are called anterior horn cells. From the anterior horn cell, a single axon goes on to innervate many muscle fibers within a single muscle. The properties of these muscle fibers are nearly identical, allowing for controlled, synchronous movement of the motor unit upon depolarization of the lower motor neuron. 2-Beta motor neurons are poorly characterized, but it has been established that they innervate both extrafusal and intrafusal fibers. 3-Gamma motor neurons innervate muscle spindles and dictate their sensitivity. These neurons primarily respond to stretch of the muscle spindle. Despite being named a “motor neuron,” these neurons do not directly cause any motor function. It is thought that they get activated along with alpha motor neurons and fine-tune the muscle contraction (alpha-gamma coactivation). A disruption in either alpha or gamma motor neurons will result in a disruption of muscle tone .

40. 1- Nusinersen = Spinraza ---- $625,000 to $750,000 in the first year, and then around $375,000 every year after . 2- Risdiplam = Evrysdi --- $382,500 3- Onasemnogene abeparvovec = Zolgensma --- $2.1 million

41. Myopathies Definition Myopathies are disorders with structural changes or functional impairment of muscle. It does not include upper motor neuron lesions, lower motor neuron lesions, myasthenia gravis which also causes muscle weakness.

42. Dystrophinopathies include 1- Severe form of disease known as Duchenne Muscular Dystrophy DMD 2- Milder form , called Becker muscular dystrophy (BMD). Both are inherited as X linked . progressive muscle diseases resulting from a defect in the dystrophin gene (DMD) resulting in a complete (DMD) or partial (BMD) deficiency of the dystrophin structural protein. incidence of 1 in 3500 boys DMD incidence of 1 in 18,000 Boys BMD

43. Treatment of DMD : 1- Exercise , physiotherapy , wheelchair , occupational therapy . 2- Corticosteroids prednisone 0.75 mg/kg/d or deflazacort 0.9 mg/kg/d is recommended to be started at 4 to 6 years of age 3- Ataluren = Translarna 4- Creatine supplements 5- Treating swallowing problems 6- Treating heart complications 7- Corrective surgery

44. Treatment of Myopathies

45. Cardiomyopathy being the Main Cause of Death in these patients

46. Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of childhood or adult-onset muscular dystrophies causing progressive proximal muscle weakness and rarely spreading to involve distal muscles as well as bulbar muscles. Over 40 different types have been identified. Treatment is supportive and should be tailored as much as possible to each individual and specific type of LGMD. Management to prolong survival and improve the quality of life includes weight control, physical therapy, and stretching exercises to improve mobility and prevent contractures; use of mechanical aid to improve ambulation and mobility; orthopedic referral for foot deformity and scoliosis; cardiopulmonary monitoring; and social and emotional support.

47. Trisomy 21

48. CDC : Down syndrome continues to be the most common chromosomal disorder. Each year, about 6,000 babies are born with Down syndrome, which is about 1 in every 700 babies born.

49. Types of Down Syndrome There are three types of Down syndrome. People often can’t tell the difference between each type without looking at the chromosomes because the physical features and behaviors are similar. 1- Trisomy 21 : About 95% of people with Down syndrome have Trisomy 21. With this type of Down syndrome, each cell in the body has 3 separate copies of chromosome 21 instead of the usual 2 copies. 2- Translocation Down syndrome : This type accounts for a small percentage of people with Down syndrome (about 3% ). This occurs when an extra part or a whole extra chromosome 21 is present, but it is attached or “trans-located” to a different chromosome rather than being a separate chromosome 21. 3- Mosaic Down syndrome : This type affects about 2% of the people with Down syndrome. Mosaic means mixture or combination. For children with mosaic Down syndrome, some of their cells have 3 copies of chromosome 21, but other cells have the typical two copies of chromosome 21. Children with mosaic Down syndrome may have the same features as other children with Down syndrome. However, they may have fewer features of the condition due to the presence of some (or many) cells with a typical number of chromosomes.

50. Diagnosis Prenatal Trisomy 21 may be diagnosed through direct analysis of fetal chromosomes, by karyotype or DNA microarray, obtained from amniocentesis, chorionic villus sampling, or percutaneous umbilical blood sampling. Use standard operating procedures to decide whether to accept prenatal diagnoses without postnatal confirmation (e.g. in cases of termination of pregnancy or unexamined fetal death). With trisomy 21, second-trimester maternal serum levels of AFP and unconjugated estriol are about 25 percent lower than normal levels and maternal serum hCG is approximately two times higher than the normal hCG level. The Triple Test is usually performed at 15 to 18 weeks of gestation . Postnatal Trisomy 21 can be strongly suspected or diagnosed clinically during the neonatal period by recognizing the typical physical traits. Clinical diagnosis should be confirmed by genetic testing (typically, karyotype from infant’s blood or tissue).

51. Types of Karyotype tests 1- Blood test which is the most common way to perform chromosome testing in adults, infants and children. 2- Bone aspiration and biopsy which tests a sample of bone marrow in people with certain cancers or blood disorders. 3- Amniocentesis which takes a sample of amniotic fluid. This is the protective fluid that surrounds the developing fetus. 4- Chorionic villus sampling (CVS) which takes a sample of cells from the placenta. This is an organ that develops in the uterus during pregnancy to provide oxygen and nutrients to the fetus.

52. Conditions or Disorders are Commonly Associated with Down Syndrome : 1- Heart defects – 50% have CHDs 2- Vision problems -- More than half of children with Down syndrome have vision problems, including cataracts , near-sightedness, "crossed" eyes, and rapid, involuntary eye movements. 3- Hearing loss. Up to three-quarters of children with Down syndrome have some hearing loss. also tend to get a lot of ear infections. 4- Infections. Infants with Down syndrome have a 62-fold higher rate of pneumonia, Caregivers also should make sure that children with Down syndrome receive all recommended immunizations to help prevent certain infections. 5- Hypothyroidism 6- Blood disorders.—leukemia , anemia 7- Hypotonia 8- Problems with the upper part of the spine.—atlantoaxial instability 9- Disrupted sleep patterns and sleep disorders. 10- Gum disease and dental problems. 11- Epilepsy. 12- Digestive problems. 13- Celiac disease. 14- Mental health and emotional problems.

53. Treatment Down syndrome is a lifelong condition. Services early in life will often help babies and children with Down syndrome to improve their physical and intellectual abilities. Most of these services focus on helping children with Down syndrome develop to their full potential. These services include speech, occupational, and physical therapy, and they are typically offered through early intervention programs in each state. Children with Down syndrome may also need extra help or attention in school, although many children are included in regular classes.

54. إرشادات منظمة الصحة العالمية التي يجب اتباعها لتجنب الإصابة بالأمراض الوراثية : 1- عدم زواج الأقارب ، لإحتمالية إنجاب أطفال مصابين بالأمراض الوراثية. 2 - اللجوء إلى المراكز الطبية المتخصصة ، لإجراء دراسة مفصلة للتاريخ المرضي للعائلة ، وإجراء التحاليل الطبية والوراثية اللازمة قبل الزواج. 3- يجب على السيدات خلال فترة الحمل ، تجنب التعرض للملوثات البيئية ، مثل الإشعاع أو الكيماويات أو المبيدات ، أو تناول العقاقير الطبية دون إستشارة الطبيب . 4 - إتباع أنظمة غذائية صحية ، تحتوي على الفواكه ، والخضرات ، والحبوب الكاملة ، فضلًا عن الأطعمة الغنية بالبروتين. 5- غسل الخضروات والفواكه جيدًا قبل تناولها. 6- مكافحة السمنة ، التي تتسبب في الإصابة بالسكري وأمراض القلب. 7- الإقلاع عن التدخين . 8- التقليل من التعرض للتدخين السلبي 9- ممارسة التمارين الرياضة بشكلٍ منتظم، لتنشيط الدورة الدموية ومنعًا لزيادة الوزن.

55. Thank You