Deficiency of tenascin-X causes abnormal elastin fiber morphology and reduced collagen levels in the dermis.17 Haploinsufficiency of TNXB causes the hypermobile type of Ehlers–Danlos syndrome, which is more prevalent in females compared to males.18,19 This connective tissue disorder subtype is characterized by joint hypermobility and easy bruising, both symptoms of lipedema.19 Our study is the first exomewide analysis to identify ECM-related rare genetic variants in families with lipedema. Here, TNXB is linked to connective tissue disorder.