Clinical Genetics Services for Haemophilia This report on Clinical Genetic Services for Haemophilia has been compiled by the Genetics Working Party on behalf of the United Kingdom Haemophilia Centre Doctors’ Organisation. Review Date: May 2018 Contents Preface…………………………………………………………………………………………5 Executive Summary .................................................................................................................... 6 Membership of Working Party ................................................................................................... 8 Section 1. Introduction .............................................................................................................. 9 1.1 Genetic counselling ...................................................................................................... 9 1.2 Confidentiality and clinical records ........................................................................... 10 1.3 Information and Informed Consent ............................................................................ 10 1.4 Carriers of haemophilia .............................................................................................. 10 1.5 Genetic testing of children ......................................................................................... 10 1.6 UKHCDO Genetic Laboratory Network.................................................................... 10 1.7 Required resources ..................................................................................................... 11 1.8 Levels of evidence ...................................................................................................... 11 1.9 Future ......................................................................................................................... 11 Section 2. Provision of services .............................................................................................. 12 2.1 Setting the scene ......................................................................................................... 12 2.2 Ensuring quality of genetic healthcare services ......................................................... 12 2.3 Recommendations ...................................................................................................... 14 2.4 Practical issues ........................................................................................................... 14 Section 3. Consent and written information............................................................................ 16 3.1 Introduction ................................................................................................................ 16 3.2 Process ........................................................................................................................ 16 3.3 Information ................................................................................................................. 17 Section 4. Data management ................................................................................................... 18 4.1 Family genetic records ............................................................................................... 18 4.2 Genetic Family Recall systems .................................................................................. 19 4.3 Contacting relatives to offer genetic counselling ....................................................... 19 4.4 Storage of data and sharing of that data. .................................................................... 20 4.5 Access to records of a relative.................................................................................... 20 4.6 Disclosure of information about a relative without consent ...................................... 21 4.7 Genetic testing in persons unable to give consent...................................................... 22 Page 2 Section 5. Pregnancy and prenatal diagnosis .......................................................................... 23 5.1 Confirmation of diagnosis .......................................................................................... 23 5.2 Counselling................................................................................................................. 23 5.3 Prenatal diagnosis ....................................................................................................... 24 5.4 Invasive prenatal diagnostic tests ............................................................................... 25 5.4.1 Chorionic villus sampling ................................................................................... 25 5.4.2 Amniocentesis ..................................................................................................... 27 5.4.3 Third trimester amniocentesis ............................................................................. 28 5.4.4 Cord blood sampling ........................................................................................... 28 5.5 Non-invasive prenatal diagnostic tests ....................................................................... 30 5.5.1 Ultrasound Assessment ....................................................................................... 30 5.5.2 Free fetal DNA in the maternal circulation ......................................................... 30 5.5.3 Preimplantation genetic diagnosis ...................................................................... 31 5.6 Termination of pregnancy .......................................................................................... 32 Section 6. Genetic testing in children ..................................................................................... 34 6.1 Males with haemophilia ............................................................................................. 34 6.2 Females who are potential carriers ............................................................................. 34 Section 7. The Clinical - Laboratory Interface ....................................................................... 37 7.1 Liaison and communication ....................................................................................... 37 7.2 Requests for Genetic Testing ..................................................................................... 37 7.2.1 Sample requirements and patient identification: ................................................. 38 7.3 Mutation Data ............................................................................................................. 38 7.4 Laboratory Database .................................................................................................. 39 7.5 Laboratory Reports ..................................................................................................... 39 7.6 Mutation databases on the Internet............................................................................. 40 Section 8. Genetic Diagnosis and Management of complex cases ......................................... 41 8.1 No mutation detectable using standard techniques .................................................... 41 8.2 Using probability to inform potential carriers ............................................................ 42 8.3 Mosaicism .................................................................................................................. 42 8.4 Females with haemophilia .......................................................................................... 43 8.5 Novel mutations ......................................................................................................... 44 8.6 Testing of carriers in the absence of an affected individual ....................................... 44 Page 3 Appendix I…. ........................................................................................................................... 46 Appendix II ............................................................................................................................... 49 References……………………………………………………………………………………50 Page 4 Preface During the intervening period since the previous second edition of these guidelines (Ludlam et al, 2005), there have been both significant developments in laboratory genetic techniques and also an increasing awareness of the importance of demonstrating and enhancing the quality of the clinical service. These revised guidelines describe the value of new scientific techniques, such as the use of free fetal DNA in the maternal circulation to determine the sex of the developing embryo, and the potential place for pre-implantation genetic diagnosis. The importance of the quality of genetic counselling, although considered in the previous edition, is given further space here particularly in relation to the training of those who provide the service and the arrangements for helping consultees. An enhanced section on issues around the genetic testing of children offers guidance to those who may be faced with requests from parents requesting genetic testing of girls who are at risk of being carriers. Perhaps the principal message of this guideline is that there must be not only high quality of care by each member of the healthcare team but that the members of the extended team must work seamlessly together. This collaboration is not only between those providing clinical care and counselling for haemophilia and other clinical services, e.g. obstetric, but also there must be a close and defined working relationship with those with responsibility