Diabetic Medicine | 2021
Basic and clinical science posters: Neuropathy
Abstract
Objective: It is not known whether syndromic subtypes of monogenic diabetes should be routinely tested in patients with suspected MODY irrespective of clinical features. Methods: We sequenced 26 monogenic diabetes genes (including 17 genes causing syndromic diabetes) and the mitochondrial m.3243A>G mutation in 1277 probands referred for MODY genetic testing and lacking clinical features suggestive of a specific subtype. We compared clinical features of patients with syndromic subtypes to nonsyndromic subtypes, and to patients with the same syndromic subtype identified by clinically selected genetic testing. Results: 294/1277 (23%) probands had monogenic diabetes. 56/294 (19%) of these had a syndromic subtype. m.3243A>G (n = 23) and HNF1B (n = 18) were the fourth and fifth most common causes in patients referred for MODY testing. No patient with m.3243A>G or HNF1B diabetes had typical syndromic features. Only 3/23 (13%) of patients with m.3243A>G diabetes reported a personal or family history of deafness compared to 52/55 (95%) identified by clinically selected m.3243A>G testing (p < 0.0001). Renal structural disease was not reported in HNF1B diabetes patients but was reported in 45/50 (90%) patients identified by clinically selected HNF1B testing (p < 0.0001). Syndromic subtypes as a group compared to nonsyndromic subtypes had similar diabetes features (age diagnosis, BMI and HbA1c) but were less likely to have a parent with diabetes (57% vs. 81%, p < 0.0001) and more likely to have additional extrapancreatic features (23% vs. 6%, p < 0.0001). Conclusions: Syndromic subtypes are relatively common in patients referred for MODY testing and should be routinely tested even if patients lack syndromic clinical features. Basic and clinical science posters: Neuropathy