Microcephaly, Epilepsy, and Diabetes Syndrome 1: A Moroccan Case Report of Novel Compound Heterozygous <i>IER3IP1</i> Mutations and Literature Review

Abstract

Abstract Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1) is a very rare autosomal recessive neurodevelopmental disorder (OMIM#614231) characterized by the triad microcephaly with simplified gyration, neonatal permanent diabetes and infantile epileptic encephalopathy. Its occurrence is due to biallelic mutations in the IER3IP1 gene, which encodes for the Immediate Early Response 3 Interacting Protein 1 (IER3IP1). To date, only eleven cases have been reported worldwide. Here, we describe the twelfth case from northern Morocco. This 4-month-old patient, born to a healthy non-consanguineous couple presented with microcephaly, epileptic seizures and insulin-requiring permanent neonatal diabetes. Brain MRI revealed simplified gyration with partial agenesis of the corpus callosum. Targeted next generation sequencing identified the patient as compound heterozygous for two IER3IP1 variants; a novel nonsense mutation, p. Leu79Ter, and a previously reported pathogenic variant, p. Val21Gly. This report extends the phenotypic and genotypic spectrum of MEDS1 syndrome and provides further evidence of the role of IER3IP1 in neural and pancreatic development, emphasizing the clinical importance of genetic screening in cases of early-onset diabetes and epilepsy especially when accompanied by significant head growth failure in a newborn infant. Further research into the pathophysiology of IER3IP1 may potentially lead to new therapeutic approaches.