In-frame pathogenic variants leading to a cysteine loss at the protein level (−Cys) and thus resulting in loss of disulfide bridges within given fibrillin-1 modules were associated in our series with severe phenotypes: 73% lifelong risk of aortic dissection or surgery (Fig. 1), severe scoliosis frequency similar to that of PTCs (45%), and high risk for the need of ectopia lentis surgery (43%, Table 1). Here, FBN1 is linked to scoliosis.