Page 17 - Clinical variability in Noonan syndrome with emphasison ear and eye
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INTRODUCTION
Figure 1. Ras/MAPK pathway
Skin features seen in Noonan syndrome are abnormalities in pigmentation (pigmented naevi, café-au-lait spots, lentigines, and keratosis pilaris). Approximately one third of patients have thick, curly hair, and 10% have thin, sparse hair (14).
Etiology and genetics
Noonan syndrome is a genetically heterogeneous autosomal dominant disorder and the incidence is reported to be between 1 in 1000 and 1 in 2500 live births (13,14). Noonan syndrome is part of the RASopathies and the most common syndrome in the RASopathy group. The RASopathies are a clinically defined group of syndromes caused by germline mutations in genes that encode components or regulators of the Ras/ mitogen-activated protein kinase (MAPK) pathway (67). The Ras/MAPK pathway (Figure 1) is one of the best-studied signal transduction pathways and it influences essential developmental processes. Ras proteins are small guanosine nucleotide-bound GTPases and they are activated by extracellular growth factors binding to receptors (including receptor tyrosine kinases (RTK’s), cytokine receptors and extracellular matrix receptors). Ras proteins switch between an active GTP-bound (guanosine triphosphate) form and an inactive GDP-bound (guanine diphosphate) form. Binding of growth factors and RTK’s
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