Search

An 18-year-old female with palmoplantar keratoderma, hyperhidrosis, facial verruciform papillomatosis, coarse face, growth retardation and developmental delay presented to our outpatient clinic. A diagnosis of Costello syndrome was made, and genetic counseling and a molecular genetic analysis were initiated. By this means, a heterozygous missense mutation in exon 2 of the HRAS gene, designated c.34GA (p.Gly12Ser), was detected, confirming the clinical diagnosis. Costello syndrome belongs to the group of clinically and genetically heterogeneous RASopathies with cutaneous symptoms. Collectively, the RASopathies are caused by mutations in different genes, which lead to dysregulation of the RAS/MAPK (mitogen-activated protein kinase) signaling pathway. This signaling route regulates the delicate balance between cell proliferation and differentiation, and plays an important role in embryogenesis and carcinogenesis. In the RASopathies with cutaneous symptoms, overlapping clinical findings may hamper making an accurate diagnosis. Therefore, a molecular genetic analysis may be useful, as in the patient described here.