RAS-MAPK pathway disorders: important causes of congenital heart disease, feeding difficulties, developmental delay and short stature.
The disorders described as the neuro-cardio-facio-cutaneous conditions (NCFCs) may all present with symptoms that are common in paediatric practice. They result from germline mutations in genes encoding kinases and other proteins interacting in the RAS-MAPK pathway. This review summarises these disorders, discussing their presenting features and clinical course, identifying overarching similarities and, conversely, features that can help to discriminate one condition from another. The genetic basis and importance of precise clinical diagnosis and molecular diagnostic confirmation when possible is discussed, given each condition's different prognosis, and the need to remain vigilant for specific complications.
Wright
Emma M M Burkitt
EM
University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, UK. bronwyn.kerr@cmft.nhs.uk
Kerr
Bronwyn
B
D000015:Abnormalities, Multiple / Q000235:genetics*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D019959:Feeding and Eating Disorders of Childhood / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020935:MAP Kinase Signaling System / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D013577:Syndrome