CLINICAL (MEDICAL) GENETICS Medical Genetics (M1 - M4) M1 : Core 2 M2 : Neuro-genetics (Neurology-Opthalmology - Psychiatry Core) M3 : Pediatrics Clerkship, Integrated workshop M4 : Family Practice Clerkship Medical Genetics within Core 2 Tests Lecture materials and Text Text Gelehrter, Collins, Ginsburg : Principles of Medical Genetics Faculty Eudy, Schaefer, Rizzo Page 1
Genetics in Clinical Medicine Congenital Anomalies An estimated 2-3 % of all newborns have a recognizable congenital anomaly An additional 2-3 % have anomalies not recognizable at birth Neuro-developmental Disorders 3% US population is mentally retarded (80% of these are genetic in origin) Learning disabilities in 5% of school age children Genetics in Clinical Medicine Adverse reproductive outcomes Infertility Spontaneous miscarriages Low birth weight Genetic basis of common disorders Cancer Vascular occlusion Hypertension Diabetes Autoimmune disorders Genetics in Clinical Medicine Public Health Environmental exposures Population screening Page 2
Definitions Medical / Clinical Genetics Genetic Counseling Cytogenetics Molecular Genetics Definitions Genetic Hereditary Familial Genetic Abnormalities are Ubiquitous Genetically we are more similar than different Only 1% of our DNA codes is different It is estimated that everyone has 5-8 genes (out of approximately 100,000) that are abnormal i.e.. recessive mutations As the genetic basis of common disorders are worked out, none of us may be free from genetic disease Page 3
Mutations are common events Average mutation rate = 10-5 to 10-6 per locus per generation Estimates of 50,000 to 100,000 genes in the genome suggests at least one in 10 persons receives a newly mutated gene from one or the other parent (germinal mutation) Somatic mutations occur with a frequency of certainty in every individual The Human Genome Project What is it? How is it going? What can we expect to get out of it? What happens when it is done? Project goals are to identify all of genes coded for 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, transfe related technologies to the private sector, and address the ethical, legal, and social issues (ELSI) that may arise from the project. Page 4
Insights from the Genome Project Number of genes Before project commonly estimated at ~100,000 Genome Project estimates 35 40,000 Recent data 70,000 "In my view, the final number of genes - when it is known - will lie somewhere between their high of 40,000 and our value of 70,000." Principles of Genetic Counseling Family Issues Assignment of fault Whose information is it? Paternity Consanguinity Page 5
Concept of Fault Not on our side of the family Mothers often bear the larger portion of the brunt Whose Information Is It? Right not to know Family members dependent on others information Legal dilemma whose rights supercede whose New HIPPA regulations Paternity Estimated 5-15% of all children have nonpaternity By nature, many molecular genetic test indirectly provide paternity information - informed consent important Mistaken paternity can result in errant genetic test results Page 6
Consanguinity Mating of closely related individuals Delicate issue Prevalence varies greatly by region(s) geographic, ethnic, or religious factors Increases risk of autosomal recessive disorders Communication Issues Provide information only Explanation of difficult concepts Perceptions of problems / needs Sensitive nature of issues Provide Information Non-directive counseling (?) truly possible (?) truly the ideal Page 7
Explanation of Difficult Concepts Patients vary greatly on level of understanding Stress of situation may cloud interpretation / retention Current technology can be quite complicated Your child has Fragile - X syndrome which is an X- linked semidominat trait that shows genetic anticipation due to an expanding trinucleotide repeat in the FMR-1 gene Insert cartoon on 10% Perception of Problems / Needs Families vary greatly in their perceptions of disease burden Families vary greatly in their concepts of the magnitude of risk Page 8
Sensitive Nature of Genetic Disorders Strict adherence to confidentiality and sensitivity are part of all practices of medicine Because of the familial implications and sometimes spectacular events in genetic disorders, meticulous attention needs to be given to confidentiality and release of information Psychosocial Issues Guilt Financial / resources Crisis intervention Guilt Real e.g. Fetal Alcohol Syndrome Perceived maternal anxiety over prenatal care unique medical issues in the family Page 9
Financial / Resources Special Health Care Needs (CSHCN) present many added stresses to families financial loss of insurance time off work (multiple specialists) fear / jealousy of siblings need for respite public curiosity / meddling Crisis Intervention The birth of a child with congenital anomalies represents a loss - of the perceived normal child typical stages of grieving The diagnosis of a genetic disorder in a family may exacerbate existing conflicts / tension Extremely high divorce rate after diagnosis Page 10