Juvenile systemic sclerosis (jSSc) and juvenile dermatomyositis (JDM) are rare autoimmune connective tissue diseases that affect the skin and internal organs. Children with jSSc experience skin thickening and ulceration, blood vessel spasm, and impaired gastrointestinal function. Children with JDM also experience blood vessel and muscle abnormalities as inflammation which causes weakness, skin rashes, and impaired gastrointestinal function. Overlap patients experience both jSSc and JDM symptoms, and some studies support more frequent lung disease and calcium deposits, but studies on these patients are extremely limited. Early intervention is essential for minimizing long-term consequences for children. Identifying genes and molecules in overlap patients may help us understand why it occurs and identify therapeutic targets. Our centers are well equipped to investigate this condition due to the expertise of the investigators and access to their data and biospecimen registries: the National Registry of Childhood Onset Scleroderma and Lurie Children’s Cure JM Registry.