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M1: Clinical Genetic Services MT CYTO CYTOGENETICS MR. ANGELICO G. REYES MEDICAL GENETICS GENETIC DISEASES ★ MEDICAL GENETICS...

M1: Clinical Genetic Services MT CYTO CYTOGENETICS MR. ANGELICO G. REYES MEDICAL GENETICS GENETIC DISEASES ★ MEDICAL GENETICS It is the study of human biological variation and TYPES OF GENETIC DISEASE its relationship to health and disease. 1. AUTOSOMAL DOMINANT INHERITANCE It includes: mechanisms of inheritance, cytogenetics, molecular genetics, and formal, statistical, and population genetics. ★ CLINICAL GENETICS It is involved in the diagnosis and management of genetic disorders affecting individuals and their families. SIGNIFICANT MILESTONES IN MEDICAL GENETICS FEATURES Affected children usually have Counseling Established in the USA during 1941, and in affected parents. Clinics the UK in 1946. No skipped generations. There is a 50% chance of a child Gregor Described the pattern of inheritance inheriting the gene from an affected Mendel recognized in human disorders. parent. Archibald Recognized the inheritance pattern of There is no carrier state. Garrod Alkaptonuria as autosomal recessive. Males and females are equally likely to transmit the phenotype and to be Hardy- Established population genetics as a affected. Weinberg basis for calculating carrier frequencies Usually arises via new mutations. Principle for autosomal recessive disorders. COMMON ➔ Achondroplasia (Dwarfism) DNA Discovered by Friedrich Meischer in 1867. DISEASES ➔ Huntington Disease ➔ Charcot-Marie-Tooth Disease Walter First illustration of chromosomes. ➔ Marfan Syndrome Flemming ➔ Von Willebrand Disease James V Described sickle cell anemia as an 2. AUTOSOMAL RECESSIVE INHERITANCE Neel autosomal recessive trait. Linus Identified sickle cell anemia as a Pauling molecular disease. JBS Estimated the mutation rate in humans Haldane based on analysis of 7 human diseases. Theodor Recognized the individuality of Boveri chromosomes related to changes in FEATURES Affected children may have chromosomes to the causes of cancer. unaffected parents. Has skipped generations. George Proposed the “One Gene–One Enzyme” There is a 25% chance of a child Beadle hypothesis in 1941. developing the phenotype by inheriting the gene from two carrier 1  parents. 4. MITOCHONDRIAL INHERITANCE The AR phenotype is seen more commonly with in-breeding. Males and females are equally likely to transmit the phenotype and to be affected. Many AR diseases do not arise via FEATURES There is a 100% chance of all mutations. off-spring developing the COMMON ➔ Albinism phenotype by inheriting the gene DISORDERS ➔ Cystic Fibrosis from an affected female parent. ➔ Hemochromatosis Only females will transmit the ➔ Sickle Cell Anemia phenotype. ➔ Thalassemia There is no male transmission of disease. 3. X-LINKED RECESSIVE INHERITANCE Males and females are equally affected by the disease. COMMON ➔ Leber Hereditary Optic Neuropathy DISORDERS ➔ Mitochondrial Myopathies (MERRF, MELAS) 5. CHROMOSOMAL DISORDERS FEATURES Affected children may have unaffected parents. Has skipped generations. There is a 50% chance of a male child developing the phenotype by inheriting the gene from a carrier female parent. FEATURES a. Structural Abnormalities Only females will transmit the b. Abnormalities of Chromosomal phenotype although males can Number transmit the gene, thereby leading to Generally rise from meiotic carrier states in female offspring. nondisjunction (failure of chromosome There is no male-to-male pairs to separate during cell division) or transmission. through anaphase lag (loss of Males, with only one X chromosome, chromosome during cell division). are more commonly affected because only one altered copy of the COMMON ➔ Angelman Syndrome gene is required to cause disease. DISORDERS ➔ Edward Syndrome ➔ Down Syndrome COMMON ➔ Duchenne Muscular Dystrophy ➔ Klinefelter Syndrome DISORDERS ➔ Glucose-6-Phosphatase Deficiency ➔ Patau Syndrome (G6PD) ➔ Prader-Willi Syndrome ➔ Fragile X Syndrome ➔ Turner Syndrome ➔ Hemophilia A ➔ XYY Syndrome ➔ Hemophilia B 2  CLINICAL GENETIC SERVICES Prenatal ➔ Ultrasound Diagnosis ➔ Fetal Echocardiography ★ GENETIC CLINIC ➔ Amniocentesis a. Confirmation if a genetic disorder is ➔ Chorionic Villus Sampling suspected. b. Genetic Counselling Postnatal ➔ Routine Karyotyping c. Genetic Investigation Diagnosis ➔ Fluorescence In-Situ Hybridization d. Information Regarding Prenatal Diagnosis (FISH) Analysis Largest Genetic Services Providers in the PH ➔ Chromosomal Microarray 1. Institute of Human Genetics Analyses 2. National Institutes of Health 3. UP Manila PEDIGREE There are only ten (10) trained clinical geneticists in the Philippines and zero (0) genetic counsellors. It is a chart that diagrams the inheritance of a trait such as dominant, recessive, and x-linked GENETIC UNITS inheritance or health condition through 1. Clinical Provides clinical services and generations of a family. Genetics Unit counselling to families with or at risk Consultand of genetic disease. - The person with the appointment in the clinic. - This person is seeking genomic health ➔ Out-patient Service ➔ Genetic Metabolic Clinic information but does not have a known ➔ Mucopolysaccharidoses Clinic diagnosis of the disorder for which they are seeking consultation. 2. Molecular Conducts research to study genetic Proband Genetics Unit conditions in the population. - The affected individual who manifests symptoms of a particular disease or ➔ DNA Sequencing condition that brings the family to medical ➔ Microarray attention. ➔ Biobank 3. Biochemical Offers diagnostic testing and ★ PEDIGREE CHART SYMBOLS Genetics management. ➔ Metabolic Disorders ➔ Maple Syrup Urine Disease ➔ Phenylketonuria ➔ Hypothyroidism 4. Hemoglobin Hemoglobinopathies are disorders of opathy Unit the hemoglobin chain which may result in anemia. ➔ Structural Hemoglobinopathies ➔ Thalassemia 5. Cytogenetics Provides postnatal and prenatal Unit congenital services or neonatal screening for congenital disorders. 3  GENETIC COUNSELLING It is a communication process that deals with the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. The process aims to help the individual or family to: GENETIC ASSESSMENT a. Understand the diagnosis. b. Choose the course of action. ★ GENETIC DIAGNOSIS c. Adjust to psychosocial impact. Establishes an accurate diagnosis. Provides information about the following: DEFINITION OF TERMS 1.) Prognosis and Follow Up Diagnostic Confirms a clinical diagnosis in a 2.) Risk of Transmission symptomatic individual. 3.) Disease Prevention Parts of Genetic Diagnosis Presymptomatic Confirms that an individual will develop symptoms later in life. Susceptibility Identifies an individual at increased risk of developing the condition later ★ ESTIMATION OF RISK in life. Absolute terms for risks of developing or Carrier Identifies a healthy individual at risk transmitting particular conditions can be of having children affected by the achieved for single gene disorders. condition. For most conditions, risks are expressed in terms of probabilities calculated from pedigree data or Prenatal Diagnoses an affected fetus. based on empirical risk figures. ★ PSYCHOSOCIAL ISSUES ★ CONSANGUINITY 1.) Guilt and Blame Refers to having descended from the same Parents may blame themselves for passing ancestor — in short, incest. the genes to their children. Consanguinity is most commonly associated with 2.) Reproductive Decision-Making inborn errors of metabolism, most of which are Deciding not to have children. autosomal recessive. 3.) Impact on Extended Family It increases the incidence of multifactorial Mother may be concerned that her daughter disorders such as diabetes, cardiovascular that is pregnant might also be affected. disorders, obesity, and certain types of cancer. 4.) Bereavement Reasons for human inbreeding avoidance on Losing a loved one, such as terminating siblings: pregnancy. 1. Witnessing an infant being taken care of by 5.) Long-Term Support one's mother. 2. Westermarck Effect — growing up in close proximity to a child. 4 ★ LEGAL AND ETHICAL ISSUES A. Informed Consent - A process in which healthcare providers inform a patient about the risks, benefits, and alternativeness if a given procedure. B. Genetic Test in Childhood - Refers to the dilemma in which procedures are being performed on children that are not yet of age to provide consent. C. Confidentiality - Refers to the two-way safekeeping of information such as patient diagnosis and results. D. Unsolicited Information - Finding out that a child’s father is not his real father. E. Non-Directiveness - Promotes the autonomy of the individual, and not the interest of the practitioner. If you’re scared, you do it scared. TONGOL, LANA LAINE N. 5