Costello Syndrome

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 Ras‐mitogen‐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. Costello syndrome is a severe developmental disorder characterised by postnatal growth retardation with delayed skeletal maturation, psychomotor retardation, cutis laxa, and acanthosis nigricans. Excessive mucopolysaccharides, which accumulate in cultured fibroblasts of patients with Costello syndrome (CS). Intracellular accumulation of chondroitin non-sulphate, as a cause of functional deficiency of the 67 kDa elastin binding protein, has been described in fibroblasts of patients with Costello syndrome.This gives support to the previous hypothesis of a defect in lysosomal degradation