Background: Primary lymphedema in children, especially generalized disease with facial involvement, is rare. Objective: We sought to report 3 childhood cases of lymphedema with associated neurologic findings and to provide a pathophysiologic explanation for this association. Methods: Clinical observations, electroencephalography, and neuroimaging studies were evaluated. Microcomparative genomic hybridization was performed in 1 case. Results: The 3 children had primary lymphedema of all 4 limbs and the face. This was confirmed by lymphoscintigraphy, which showed hypoplasia of vessels and hypofixation of lymph nodes. They had nonspecific neurologic disorders and electroencephalography abnormalities, without intellectual deficit. Neuroimaging revealed normal findings. Microcomparative genomic hybridization in 1 patient revealed no cytogenetic anomaly. The outcome was fatal in 1 case with development of visceral lymphedema and coma. Limitations: Genetic studies were performed in only 1 case. Conclusion: These observations suggest that neurologic assessment and electroencephalography are indicated for patients with lymphedema of the limbs and face to identify this syndrome.