The absence of lymphoedema in both parents, the congenital onset and persistent nature of the affected individuals' lymphoedema and the absence of additional clinical features such as distichiasis, microcephaly, chorioretinopathy, intellectual disability, hypotrichosis, telangiectasia and lack of mutations in all genes previously associated with other known forms of inherited primary lymphoedema strongly suggest that the symptoms are part of a novel clinical entity termed PIEZO1-associated hereditary lymphoedema. Here, PIEZO1 is linked to lymphedema.