Podoconiosis: an important but forgotten cause of non-filarial lymphoedema

Podoconiosis is a preventable, non-infectious and non-communicable cause of lymphoedema leading to chronic swelling of the foot and lower leg. Most prevalent in Africa, Central America and India, it is caused by long-term exposure to irritant red volcanic clay soil. Risk factors for disease are related to the absence or inadequacy of footwear. However, not all those at risk develop the disease, indicating that both genetic and environmental predispositions contribute to disease development. Symptoms of podoconiosis include asymmetrical limb swelling with associated itching, burning sensation and lymphatic ooze. Late stages are characterised by irreversible swelling and joint fixation. Due to the disfiguring nature of the disease, those affected often experience social stigmatisation. Associated economic losses result from reduced productivity and absenteeism. The disease must be differentiated from conditions such as filarial lymphoedema and congenital lymphoedema, which can have similar presentations, such that appropriate therapy can be implemented. Primary management of podoconiosis is prevention which involves the regular use footwear such as shoes and education of the disease. In the early stages of podoconiosis, compression therapy and limb elevation delays clinical progression in affected individuals. In later stages, changes are irreversible; however, additional therapy can include surgical intervention and limb elevation for symptom control. Psychosocial care is also needed to address the mental distress associated with the disease. Despite the preventable nature of podoconiosis, it remains prevalent in developing countries, necessitating further investment of resources.

A novel mutation in the conserved sequence of vascular endothelial growth factor receptor 3 leads to primary lymphoedema

Objective To investigate whether lymphoedema in a Chinese family showed the hereditary and clinical characteristics of Milroy disease, an autosomal dominant form of congenital lymphoedema, typically characterized by chronic lower limb tissue swelling due to abnormal lymphatic vasculature development, and to perform mutational analyses of vascular endothelial growth factor receptor ( VEGFR)3. Methods Individuals from a three-generation family affected by congenital lymphoedema were clinically assessed for Milroy disease. Mutation analysis of VEGFR3 was performed using DNA from family members and healthy controls. Results Out of 20 family members, eight were diagnosed with hereditary lymphoedema. Mutation analyses revealed a novel mutation site for c.3163 G>A, resulting in a p.1055D>N mutation in the second tyrosine kinase domain of VEGFR3, which was present in affected individuals only (absent in all unaffected family members and 130 healthy controls). Computed functional analyses showed the mutation may lead to structural alterations with a probability of 0.99999 of being disease causing. Conclusion A novel mutation associated with Milroy disease was identified in a Chinese family, expanding our knowledge of VEGFR3 gene function and providing a potential molecular target for treating hereditary lymphoedema.