FLT4 and Milroy disease: Missense variants in the protein kinase domain reported to cause Milroy disease (hereditary lymphedema, OMIM-P 153100) provide evidence for allelic heterogeneity in FLT4. However, robust genotype–phenotype correlations are challenged by the abovementioned frameshift deletion and by a missense substitution in the protein kinase domain in an individual with isolated TOF (Fig. 1a).