Monogenic Forms of Diabetes Resulting from Beta-Cell Dysfunction

Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing beta-cell dysfunction, which accounts for the majority of cases. Patients can usually be divided into three clinical categories; maturity-onset diabetes of the young (MODY) which is dominantly inherited familial diabetes, neonatal diabetes diagnosed under the age of 6 months and monogenic diabetes syndromes which are characterized by multiple non-pancreatic features. In each clinical category there are several aetiological genes, which usually result in a discrete clinical phenotype. Genetic diagnosis is now possible in >80% of cases and is crucial in determining appropriate management, predicting clinical course, screening affected relatives, and genetic counselling of unaffected family members. Importantly, in many of the most common causes of monogenic beta-cell diabetes, making a diagnosis can result in greatly improved treatment. However diagnosis can be challenging because of low prevalence rates in a diabetes clinic (1–3%) and the majority of patients are therefore misdiagnosed as having type 1 (T1D) or type 2 diabetes (T2D). Features that distinguish these disorders are discussed.