Novel mutations in a patient with KBG syndrome and sulfonylurea unresponsive ABCC8- Maturity onset of the Diabetes in Young

Abstract

The proband was a 17-year-old girl born out of non-consanguineous marriage and delivered by vaginal delivery at 32 weeks of gestation. Gross motor skills were slightly delayed. At the age of 13 years, she was diagnosed with diabetes mellitus. There was no history suggestive of autism or attention deficit hyperactive disorders and intellectual disability. On examination, her height (HT) was 133.2 cm (< 3rd centile). The following facial features were observed: triangular facies, macrodontia, thin upper lip, synophrys, low anterior hair line, high nasal bridge, anteverted ears and long eye lashes. Hypertrichosis was present over the back, forearm and lower limbs. Importantly multiple callosities were observed over the plantar surface of each foot. Branchial sinus over the anterior margin of lower end of sternocleidomastoid muscle was detected in either side. Exome sequencing revealed that the proband had a novel heterozygous variant (Asp1187Glu) at ABCC8 and a heterozygous variant (Lys2447del) at ANKRD11. The mutations were confirmed on sanger sequencing. Her mother, who had history of gestational diabetes mellitus, had also this ABCC8 variant. Father and younger brother did not have any one of these variants. The glycaemic status of the proband did not improve with high dose of glimepiride possibly due to altered function of sulfonylurea receptor 1. Here we report a patient with KBG syndrome and sulfonylurea unresponsive ABCC8-MODY associated with second or rarely third branchial cleft anomaly and plantar callosity, which to the best of our knowledge has not been reported earlier.