Diagnosing Rare Diseases: from the Clinic to Research and back

Syllabus

• Week 1

  Introduction to the course

  • Welcome and Introduction

    You will learn what a rare genetic disease is and what are the main inheritance patterns of rare genetic diseases. You will also get introduced to what a medical diagnosis and a genetic diagnosis are.

  • What is a rare disease?

    Rare diseases are diseases which affect a small number of people compared to the general population. Specific issues are raised in relation to their rarity.

  • Are all rare genetic diseases inherited?

    About 70%-80% of rare diseases are of genetic origin. In the remaining 20 to 30%, a rare disease can be caused by factors in the environment such as drug exposure or infections or be due to autoimmunity and are not inherited.

  • Challenges met when diagnosing rare diseases

    The notion of diagnosis in medicine may seem difficult to grasp and the ease of diagnosis varies from one individual to another.

  • What do we call a diagnostic odyssey?

    A diagnostic odyssey is a term which has come to be used to refer to the period from the onset of the first symptoms to the date of a definite diagnosis.

  • The place of patients groups and organisations

    Patients organizations and groups are essential in the diagnostic process and odyssey of many rare diseases patients around the world.

  • Why is it so important to put a name to a disease?

    Putting a name to a disease is a fundamental step in the journey of the patient and his/her relatives. It enables to clarify the prognosis and the progression of the disease and also to implement the appropriate care.

  • Test your knowledge

    What have you learnt and understood this week? Test your knowledge with a multiple choice quizz and reflect on the week's content.

• Week 2

  What is the clinical diagnostic pathway for rare diseases patients?

  • Welcome and Introduction

    In this week, you will learn how a genetic consultation is held, what is the degree of evidence of a medical diagnosis as well as what are the advantages and limitations of a medical diagnosis.

  • How is a first genetic consultation held?

    In this first part, you will learn how a first genetic consultation is prepared and run. The first genetic consultation is the initial step of the geneticist’s investigation.

  • Consenting to genetic testing - practical, ethical and research issues

    In most European countries, a genetic test is subject to a written informed consent containing quite similar information from one European country to another.

  • Medical diagnosis and genetic diagnosis: degree of evidence and challenges

    As you have seen in week 1, three main diagnostic situations (obvious, probable, unknown) can be found in genetics that we are recapitulating and detailing further this week.

  • Diagnosing rare diseases in Europe - collaborations and realities

    Over 30 million Europeans are concerned by a rare disease. How does the EU meets the challenge? Are there differences in addressing the challenge from on EU country to another?

  • Test your knowledge

    What have you learnt and understood this week? Test your knowledge with this quiz! Take also the opportunity to reflect on the week.

• Week 3

  Diving into analysis and interpretation of genetic results

  • Welcome and Introduction

    From prescribing of a genetic test to reporting the results of a genetic test: what happens? what are the challenges met?

  • What are the available tests to diagnose a rare disease?

    You will learn about the tests available in a medical setting to diagnose a rare disease (presumably of genetic origin). You will see the challenges, performance, advantages and disadvantages raised by each of them.

  • Genetic testing in practice

    We will now see more concretely how it works in the genetics clinics practice.

  • How NGS techniques have been a game-changer in clinical genetic services?

    You will now learn about how NGS techniques have been game changers when diagnosing a genetic rare disease.

  • Explanation of the human genome variability and the challenges met when interpreting data

    The human genome has not had as much time to accumulate genetic variation as have the vast majority of species on earth. Nonetheless, there is considerable genetic variation in our species.

  • What are prediction tools?

    The variants and regions of the human genome can be annotated with tens of data sources.

  • Basic principles of bioinformatics and biological analysis

    You will now get introduced to the basic principles of bioinformatics and biological analysis of databases to support the genetic analysis.

  • Multidisciplinarity is the key

    In this item, you will learn how multidisciplinary approaches are essential and rapidly developing in the genetic diagnosis of rare diseases, namely in the context of European Reference Networks (ERN).

  • Reporting results to patients

    You will now learn about five different situations that can be met in the clinical diagnostic practice when reporting the results to the patients.

  • Test your knowledge

    What have you learnt and understood this week? Test your knowledge with this quiz! Take some time to reflect on the week as well.

• Week 4

  What are the research steps to reach a diagnosis?

  • Welcome and Introduction

    When a diagnosis could not be found after state of the art clinical diagnostic tests and process: what research can offer to finally reach a diagnosis for undiagnosed patients?

  • Specific research challenges of cases without diagnosis

    Not finding a diagnosis in a clinical setting should lead to the development of research activities. Those will differ depending if a Variant of Uncertain Significance (VUS) has been identified or not.

  • Reclassification of Variants of Uncertain Significance

    We will explain why researchers should reassess gene tests results to declassify and/or reclassify variants.

  • Family co-segregation

    Understand and exercise around family co-segregation

  • What is clinical and functional reassessment?

    Clinical reassessment can have a role to play in different situations and can lead to the prescription of complementary investigations.

  • How to overcome negative exomes?

    How new research techniques and perspectives can overcome negative exomes.

  • Omics approaches in the diagnosis of rare diseases

    In this subactivity you will get introduced to the different omics approaches. You will understand what they involve and how they can be beneficial in enhancing the diagnosis and treatment plans for rare diseases.

  • Importance of international collaborations

    International collaborations and initiatives are key to tackle undiagnosed rare diseases.

  • Test your knowledge

    Time to assess what you have understood this week and to reflect on the topics of the week.

• Week 5

  What's next after the search for a diagnosis?

  • Welcome and Introduction

    Welcome to the last week of this course! This week opens the reflection to related-research fields that would help grasp both the challenges and the opportunities when diagnosing rare diseases from other perspectives.

  • How basic pathophysiological research can improve a diagnosis?

    Basic research in medicine refers to the study of fundamental knowledge and to the understanding of biological mechanisms and processes that underlie illness and health.

  • Towards multifactorial inheritance

    Towards multifactorial inheritance: How the estimation of risks and assessing the potential role of the environment can contribute to diagnostic evaluation?

  • Next Generation Sequencing: from Diagnosis to Prevention

    Sequencing individual genomes can help detect numerous variants that may be relevant for many applications, including preventive medicine.

  • Why are rare diseases registries and databases especially important?

    To initiate clinical trials or to conduct natural history studies in rare diseases, a sufficient number of patients is often difficult to find.

  • How Social Sciences can help better understand challenges surrounding rare disease diagnosis?

    Social sciences make a significant contribution to our capacity to both understand health problems and challenges beyond medical issues. They also offer interesting avenues to explore in order to offer novel solutions.

  • Next Generation Sequencing in medical practice: can we afford it?

    NGS technologies have emerged as important alternatives to the traditional diagnostic pathway, especially with drastic cost reduction of those techniques. What does it entail from an health-economics perspective?

  • Wrap up and next steps

    A few take home messages and some information on additional training on rare diseases.

Who will you learn with?