Indian Undiagnosed Diseases Program (I-UDP) – The Unmet Need

Genomics is an integral part of many pediatric diseases spanning all sub-specialities. While many genetic disorders are diagnosed with the currently available genomic tests, there still are many patients who do not receive a definitive diagnosis. The Indian Undiagnosed Diseases Program is a multicenter effort to address these challenges and unmet needs of rare disease patients where current available genetic tests have failed to make a diagnosis. It embodies the principles of collaborative effort across multispecialty disciplines, and uses detailed phenotype. Diagnostic methods are tailored to patient specifics and the large genomic data is interrogated with precise, in-house bioinformatics pipelines using patient-specific phenotype to build the diagnostic algorithm. The inception of this research initiative in India is a step towards creating awareness and appreciation of the needs for our undiagnosed cohorts to enable appropriate management in this era of precision medicine.

Vici Syndrome with a Novel Mutation in EPG5

Background: Vici syndrome is a neurodevelopmental disorder of the autophagy pathway.Almost all cases reported have the cardinal features of agenesis of corpus callosum,cataract, cardiomyopathy, immunodeficiency and hypopigmentation. Casecharacteristics: 8-month-old boy with developmental delay, myoclonic jerks, repeatedrespiratory infections, coarse facial features, cataract and hypopigmented hair.Echocardiography revealed dilated cardiomyopathy and magnetic resonance imaging ofbrain suggested agenesis of corpus callosum. Exome sequencing detected a novelhomozygous nonsense mutation in the EPG5 gene. Outcome: Establishing a definitediagnosis helped in proper prognostication, providing genetic counseling and prenataldiagnosis to the family. Message: Though uncommon, presence of the characteristicfeatures makes Vici syndrome a clinically recognizable cause of developmental delay.