Milroy's primary congenital lymphedema in a male infant and review of the literature.

BACKGROUND: Milroy's primary congenital lymphedema is a non-syndromic primary lymphedema caused mainly by autosomal dominant mutations in the FLT4 (VEGFR3) gene. Here, we report on a 6-month-old boy with congenital non-syndromic bilateral lymphedema at both feet and tibias, who underwent molecular investigation, consisted of PCR amplification and DHPLC analysis of exons 17-26 of the FLT4 gene. The clinical diagnosis of Milroy disease was confirmed by molecular analysis showing the c.3109G>C mutation in the FLT4 gene, inherited from the asymptomatic father. This is a known missense mutation, which substitutes an aspartic acid into a histidine on amino acid position 1037 of the resulting protein (p.D1037H), described in two other families with Milroy disease. A thorough genetic molecular investigation and clinical evaluation contributes to the provision of proper genetic counseling for parents of an affected child with Milroy disease. The herein described case, which is the third reported so far with c.3109G>C mutation, adds data on genotypic-phenotypic correlation of Milroy disease. The relative literature regarding the pathophysiology, molecular basis, clinical spectrum and treatment of Milroy disease is reviewed.