Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities.

Background

Milroy disease (MD) is rare and autosomal dominant resulting from mutations of the vascular endothelial growth factor receptor-3 (VEGFR-3 or FLT4), which leads to dysgenesis of the lymphatic system.

Methods

Here we report a Chinese MD family with 2 affected members of two generations. We identified the mutation of c.3075G>A in one allele of FLT4 in Chinese population firstly. The father and child presented lymphedema under knees both. Unfortunately, the child was premature delivered for a car accident of the mother and then died of asphyxia. Then we gathered the tissue of the lower-limb from the child with permission from the parents and ethic committee. We stained the tissue with lymphatic marker D2-40 and hematoxylin-eosin to explore the histological changes. Afterwards, we compared the results with a normal child who unfortunately died of premature delivery also.

Results

It is firstly identified the mutation of FLT4: c.3075G>A in Chinese population, and the mutation Inherited in the lineage. The histological evaluation indicated: (1) The number of lymphatic vessels decreased; (2) The morphology and structure of lymphatic vessels was abnormal. And what is added to our knowledge: (1) Capillary hyperemia and phlebectasia is severe; (2) Vascular malformations; (3) The number of vascular endothelial cells and vascular smooth muscle cells decreased; (4) Large sheets of epidermis desquamated; (5) The numbers of cutaneous appendages reduced in MD.

Conclusions

Based on the new findings, we assume that mutation of FLT4 not only affect the lymphogenesis, but also the angiogenesis, and epidermis structure.