When you trace this line down to Anna Leopoldovna and her offspring, it starts to look like genetic disease (a grandson of Ivan V, son of Praskovia Ivanovna, died at the age of 4 as well, offspring of Anna Leopoldovna muddles the research but anyways, girls in this line were often MUCH healthier than boys). Though to be honest, there is no info on frail constitution of Alexis, and deaths of heirs at the early age were not that uncommon.
This is true, so perhaps, a chance for some relief there. An average reign for descendants between twenty-thirty years, health allowing