Variants in nuclear genes that encode products routed to the mitochondrion are in green print in Figure 1A and listed for the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG) in Figure 1B. The 17 POLG variants with their linkage to neuromuscular (M607459+) and dysautonomia (M612662+) symptoms [38,39], echoed by the diverse mitochondrial DNA variants of Figure 1B, suggest mitochondrial depletion with brain–muscle energy deficiency as the way in which mitochondrial dysfunction contributes to EDS. Here, POLG is linked to Ehlers-Danlos syndrome.