17q12 Recurrent Deletion Syndrome – a rare cause for diabetes mellitus type MODY5

 

Objective:

Maturity onset diabetes of the young type 5 (MODY5) represents a rare monogenetic entity of diabetes mellitus and is caused by mutations of hepatocyte nuclear factor 1 homeobox β (HNF1β). Whereas clinical characteristics and therapeutic management of MODY5 are increasingly better defined, consideration of the frequent association of MODY5 with 17q12 Recurrent Deletion Syndrome is often missed.

Methods/Results:

We report the case of a woman with 17q12 Recurrent Deletion Syndrome presenting with diabetes mellitus and abnormal liver and kidney function at the stage of diagnosis at the age of 36. The patient had mild facial dysmorphism with frontal bossing and notable intellectual disability. Diabetes mellitus was characterized by rapidly developing insulin dependence without ketoazidosis. HNF1β gene deletion was detected by molecular genetic analysis. Magnetic resonance imaging confirmed multiple renal cysts and pancreatic atrophy as common features of 17q12 Recurrent Deletion Syndrome.

Conclusion:

The 17q12 Recurrent Deletion Syndrome describes the clinical onset of MODY5 combined with structural or functional abnormalities of the kidney and neurodevelopment or neuropsychiatric disorders. HNF1β gene deletion can be found in about 50% of patients with MODY5. Since HNF1β deletions are virtually always associated with 17q12 Recurrent Deletion Syndrome and common genetic analyses for evaluation of MODY5 are often unable to detect the deletion of the 1.4 megabases gene region, initial attention of the syndromal features at the stage of diagnosis is of considerable importance. A wide variety of additional clinical features, including heart and brain malformations have already been reported and require interdisciplinary patient care.