Costello syndrome: Clinical diagnosis in the first year of life

M. Cristina Digilio, Anna Sarkozy, Rossella Capolino, M. Beatrice Chiarini Testa, Giorgia Esposito, Andrea De Zorzi, Renato Cutrera, Bruno Marino, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review


We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene. Phenotypical overlap of CS with Noonan (NS) and cardiofaciocutaneous syndrome (CFCS), particularly in neonatal age, is well known. Diagnostic features useful for recognition of CS in the first year of life are the following: (1) fetal and neonatal macrosomia with subsequent slow growth due to severe feeding difficulties, (2) developmental delay, (3) particularly coarse facial dysmorphisms and gingival hyperplasia, (4) skeletal anomalies as osteoporosis and metaphyseal enlargement, (5) hypertrophic cardiomyopathy (HCM) with asymmetric septal thickening and systolic anterior motion of the mitral valve, and (6) specific atrial arrhythmias. Following a clinical suspect of CS based on specific features, molecular screening of HRAS gene mutations should precede analysis of the other genes in the Ras-MAPK pathway implicated in related disorders with overlapping phenotypes.

Original languageEnglish
Pages (from-to)621-628
Number of pages8
JournalEuropean Journal of Pediatrics
Issue number6
Publication statusPublished - Jun 2008


  • Cardiofaciocutaneous syndrome
  • Costello syndrome
  • HRAS gene
  • Noonan syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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