17q12 microdeletion is a rare syndrome that presents with variable features resulting in long term challenges. Early surveillance is necessary for the diagnosis, and the associated with the syndrome. In this case report, we present 17q12 microdeletion syndrome in Di-Di twins born at 31 3/7 weeks gestation. wTin A presented with intellectual disability, patent ductus arteriosus, retrognathia, club feet, and seizure-like activity, and twin B presented with renal cysts, large pericardial effusion, PDA and PFO with left to right shunts. This report provides screening recommendations for renal abnormalities, maturity-onset diabetes of the young type 5 (MODY5), Autism Spectrum Disorder (ASD), developmental delay, intellectual disability, schizophrenia, and Mullerian agenesis to assist pediatricians involved in the medical care of patients with 17q12 microdeletion syndrome.