Towards Best Practice Guidelines for Genetic Testing of Monogenetic Subtypes of Diabetes Mellitus (WC2010-109)

Background

Starting date: 01/03/2011

Diabetes mellitus is mostly considered a multifactorial disease: it is assumed to result from multiple interactive genetic and environmental factors. However, monogenetic subtypes of diabetes mellitus also exist. These include maturity-onset diabetes of the young (MODY), permanent neonatal diabetes mellitus (PNDM), and maternally inherited diabetes and deafness (MIDD). MODY is the most common form of monogenetic diabetes mellitus. It describes a clinically heterogeneous group of disorders that are characterized by an onset usually before the age of 25 years, non insulin dependent diabetes and an autosomal dominant mode of inheritance. Making a diagnosis based on the clinical picture can be difficult because of similarities in presentation between types. People with MODY may therefore be misdiagnosed as type 1 or 2 diabetes. People with MODY, however, are generally not overweight and do not have other risk factors for type 2 diabetes such as abnormal blood fat levels or high blood pressure. While both type 2 diabetes and MODY run in families, people with MODY typically have a positive family history in multiple generations.

Molecular genetic testing may help in correctly classifying the diabetes subtype, predicting the likely clinical course and choosing the accurate therapeutic strategy (personalized medicine). Moreover, it may help in identifying family members at risk, who can subsequently be offered regularly monitoring and, if necessary, early treatment. In addition, family members can be exempted from medical controls when they are not at increased risk. 

In the Netherlands, the number of individuals tested for one or more MODY genes is considerably lower than would be expected based on the estimated prevalence, which may be due to the lack of any translational research and guidelines. In the current study, we therefore aim to develop consensus guidelines by providing a platform for experts in the field and discussing their opinions on the current and best practice of genetic testing of monogenetic subtypes of diabetes mellitus, including barriers for implementations of guidelines.