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.

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.

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.

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

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.

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

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.

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

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.

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.

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

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.

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?

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

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

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.

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

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

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.

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

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

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).

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

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

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?

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.

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

Understand and exercise around family co-segregation

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

How new research techniques and perspectives can overcome negative exomes.

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.

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

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

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.

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

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

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

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.

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?

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