The causes for PWS without capillary malformations are currently unknown. Some cases of PWS are a result of mutations on the RASA1 gene which is located on chromosome 5 at position 14.3. This mutation is only applicable to patients with capillary malformations. RASA1 gene is responsible for making p120-RasGAP protein. This protein regulates the RAS/MAPK signaling pathway. RAS/MAPK signaling pathway is used for transmitting signals from the outside the cell to the cell’s nucleus. This pathway is very important as it directs cell functions such as growth, proliferation and controls the cell movement. The p120-RasGAP protein regulates the RAS/MAPK pathway by acting as a negative regulator of the signaling pathway. It turns off signals. Mutations in the RASA1 gene disrupt the normal formation of p120-RasGAP protein and result in a nonfunctional protein. The protein no longer regulates the RAS/MAPK signaling pathway. However, according to NIH Genetics Home Reference, it is still unclear how exactly the disruption of p120-RasGAP protein formation leads to vascular abnormalities and limb overgrowth. But it is a known fact that somehow p120-RasGAP protein is crucial for the normal development of the vascular system and its complex network of blood vessels such as arteries, veins and capillaries. Based on current knowledge, disruption of p120-RasGAP protein is the reason behind blood vessel malformations which in turn lead to all sorts of problems such as: overgrowth in limbs, excess blood flow near the surface of the skin which leads to port wine stains and even heart failure can occur. The severity of the symptoms is based on extent of the malformations.
Parkes Weber syndrome
Neu–Laxova syndrome
Stratton Parker syndrome
Madras motor neuron disease
Temple–Baraitser syndrome
Dejerine–Sottas disease
De Barsy syndrome
Shapiro syndrome