Genetics, Reproduction and Family Planning
https://www.youtube.com/watch?v=5GPPt0kftfE
Many genes identified in bleeding disorders Haemophilia A Haemophilia B Von Willebrand disease Semin Thromb Hemost 2019; 45(07): 695-707 DOI: 10.1055/s-0039-1687889
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during a pregnancy? • Is there are way to avoid having a pregnancy with the bleeding disorder?
Genetic counselling session https://www.massgeneral.org/tsc/patient-ed/comprehensive- care-genetic.aspx “Genetic counselling is a communication process, which aims to help individuals, couples and families understand and adapt to the medical, psychological, familial and reproductive implications of the genetic contribution to specific health conditions ” Resta et al, (2006) A new definition of genetic counelling: NSGC task force report, J Gen Couns
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during a pregnancy? • Is there are way to avoid having a pregnancy with the bleeding disorder?
Genes encode for proteins Greenwood Genetic Centre. 6 th Ed. Counseling Aids
Alteration in gene can affect production of protein https://cdn.prod-carehubs.net/n2/71b34990bba71dfd/uploads/2018/07/genemutations-aid.png
Haemophilia A • F8 gene instruction is responsible for… Important for blood Factor VIII production clotting • If there is an alteration in the F8 gene… Problem with production of normal Factor VIII Haemophilia A levels
Haemophilia B • F9 gene instruction is responsible for… Important for blood Factor IX production clotting • If there is an alteration in the F9 gene… Problem with production of normal Factor IX Haemophilia B levels
von Willebrand disease • VWF gene instruction is responsible for… Important for adhesion of von Willebrand Factor platelet plug and blood production clotting • If there is an alteration in the VWF gene… Problem with production of normal von Willebrand von Willebrand disease factor
? Family history • New genetic change • Inherited (from one or both parents)
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during pregnancy? • Is there are way to avoid having a pregnancy with the bleeding disorder?
Genes are packaged into chromosomes Greenwood Genetic Centre. 6 th Ed. Counseling Aids
The F8 and F9 gene are both found on the X chromosome
Genetics of Haemophilia • Haemophilia A and Haemophilia B – Men with gene mutation affected by condition – Women with gene mutation usually milder bleeding disorder or unaffected (carrier of haemophilia)
How can girls have haemophilia? X chromosome inactivation non functioning gene XX Very early cell division XX XX Random inactivation of X X X X X X X X one X in each cell Usually switch off roughly ‘half -half ’ - many females have mild bleeding tendency
But rarely a female will have moderate to severe bleeding ‘Skewed’ X chromosome inactivation non functioning gene XX Inactivation can XX XX sometimes be randomly ‘skewed’ one way or the .X X. X. X. other X/X X X Can have almost no cells with a functioning FVIII or FIX gene – very low factor levels and moderate to severe bleeding – similar to that seen in males
Inheritance of Haemophilia
Inheritance of Haemophilia https://ghr.nlm.nih.gov/primer/illustrations/xlinkrecessive.jpg
The VWF gene is located on chromosome 12
Genetics of von Willebrand disease • von Willebrand disease can equally affect men and women • Different types of von Willebrand disease which can be inherited in different ways and can be complex
Inheritance of von Willebrand disease
Inheritance of von Willebrand disease
Other Genetic bleeding disorders Dorgalaleh and Rad, Congenital Bleeding Disorders at https://scholar.google.com/citations?user=75MCVGgAAAAJ&hl=en&oi=sra
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during a pregnancy? • Is there are way to avoid having a pregnancy with the bleeding disorder?
Gene testing https://www.bellairetpp.org/columnseditorials/2019/05/23/ genetic-testing-our-future/ For affected person gene testing may – Confirm diagnosis – Add to understanding of likely prognosis/management – Allow or make simpler testing in other family members – Identify mutation for reproductive planning
Gene testing https://www.bellairetpp.org/columnseditorials/2019/05/23/ genetic-testing-our-future/ • Detection rate targeted diagnostic testing – 95% for haemophilia A – Greater than 95% for haemophilia B – VWD • 65% -85% depending on severity Type 1 • >90% Type 2 • 80-90% Type 3 • Beware – reproductive carrier screening panels
Carrier testing in healthy individuals • Can’t rely on factor levels alone • Genetic carrier testing can clarify chance of having an affected child & may inform pregnancy management • Inform whether need for genetic testing in other family members (cascade testing) • Genetic carrier testing for obligate carriers
Timing of carrier testing • Before / as part of family planning • Understand information and competent to consent to testing • Chance of altered self image • Open communication prior to carrier testing can make a difference
Communication of carrier status • Different for everybody • Privacy vs need/desire to share information • When to discuss with partner? • Fears about how person may respond • Delaying too long can sometimes result in mistrust/resentment • Preparing for conversations can help • Resources - Haemophilia Foundation
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during a pregnancy? • Is there are way to avoid having a pregnancy with the bleeding disorder?
Genetic testing in pregnancy • Decision to test or not to test is very personal – To inform precautions at time of delivery and neonatal period – For psychological preparation – For consideration of termination of pregnancy
Non invasive prenatal screening to determine sex of baby • Non-invasive prenatal testing (NIPT) – No risk to pregnancy – Usually performed from 10 weeks – Detects cell free DNA from fetus in http://pathcarelifesciences.com/nipt/ mothers blood – Checks sex of baby but doesn’t check for altered gene – Small chance of incorrect sex determination – U/S follow up
Chorionic villus sampling (CVS) • 11-12 weeks of pregnancy • Sample of chorionic villi (placenta) • Less than 0.5% (1 in 200) chance of miscarriage from procedure http://pathcarelifesciences.com/nipt/ • Genetic testing for familial mutation performed on specimen
Amniocentesis • 15 weeks onwards • Sample of amniotic fluid • Less than 0.5% (1 in 200) chance of miscarriage from procedure http://pathcarelifesciences.com/nipt/ • Genetic testing for familial mutation performed on specimen
Questions about bleeding disorders https://www.forbes.com/sites/work-in- progress/2019/07/08/if-you-want-to-look-smart-ask- these-questions/#59ddc2db1448 • How did this happen? • Could other family members/ future children have a similar bleeding disorder ? • Gene testing other family members? • Can we test for the bleeding disorder during a pregnancy? • Is there are way to avoid having a pregnancy affected with the bleeding disorder?
Preimplantation genetic diagnosis (PGD) Expensive, not currently Possible for almost all funded in public system in disorders/scenarios that NSW Analysis of DNA from a can be diagnosed few cells only prenatally More technically challenging than prenatal tests
Recommend
More recommend
