Since the calico belongs to almost ten different breeds, no specific health issue is associated with them. However, male calicos are prone to Klinefelter syndrome due to an additional X chromosome. Klinefelter syndrome is associated with a shorter lifespan, increased body fat, a propensity for broken bones, and behavioral problems.
This happens due to the XXY combination. Rather than XY chromosomes, males have an XXY chromosome combination, which results in Klinefelter syndrome. However, they can still lead healthy and full lives but also need some extra care.