Prof Ramachandran Muthiah
Morning star hospital, India
Title: Malignancy risk in neonatal Costello syndrome
Biography
Biography: Prof Ramachandran Muthiah
Abstract
Costello syndrome is a rare RASopathy resulting from germline mutations of the protooncogene HRAS. Many of these mutations affect SHP2, SOS1, RAS, RAF and MEK proteins It was discovered by Dr. Jack Costello, a New Zealand paediatrician in 1977. Dr. White says. Costello syndrome is now known to be one of a group of related disorders,, caused by abnormal functioning of the Rasâ€mitogenâ€activated protein kinase (RAS/MapK) pathway. Ras/MAPK pathway is an essential signaling pathway that controls cell proliferation, differentiation, survival and its dysregulation causes clinically overlapping genetic disorders, called as ‘Rasopathies’.In this pathway, Ras, a GTPase, transmits extracellular signaling from receptor tyrosine kinases to two serine/threonine kinases (Raf and MEK) and, finally, to the activation of MAPKs. Frequency of malignancy in mutation positive cases is 11%. In the Japanese and North American series, the commonest mutation was the G12S missense substitution