Kavvoura FK., Owen KR.
© 2014 Elsevier Ltd. All rights reserved. Whereas most people with diabetes mellitus have type 1 (T1DM) or type 2 diabetes (T2DM), there are other inherited forms of diabetes and insulin resistance syndromes, which represent about 2-5% of all cases of diabetes. Monogenic forms of pancreatic β-cell dysfunction include maturity-onset diabetes of the young (MODY) and neonatal diabetes (NDM), with MODY being the most common form of inherited diabetes. The long-term response to sulfonylurea drugs in MODY due to HNF1A and HNF4A mutations and NDM due to KCNJ11 and ABCC8 mutations are excellent examples of pharmacogenetics. Mitochondrial diabetes is maternally inherited and almost always associated with sensorineural deafness. Monogenic severe insulin resistance can be divided into adipose tissue defects (lipodystrophies, characterized by abnormal fat distribution) and disorders of insulin signalling. Molecular diagnosis of inherited diabetes has important implications for patients, allowing personalized management and screening of their relatives. Misclassification of monogenic diabetes or severe insulin resistance as T1DM and T2DM is common and new tools for prioritizing suspected cases for genetic testing are needed.