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Costello syndrome: clinical diagnosis in the first year of life

European Journal of Pediatrics volume 167, pages 621–628 (2008)Cite this article

Abstract

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.

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Abbreviations

CS:

Costello syndrome

NS:

Noonan syndrome

CFCS:

cardiofaciocutaneous syndrome

MRI:

magnetic resonance imaging

HCM:

hypertrophic cardiomyopathy

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Author information

Affiliations

  1. Medical Genetics, Pediatric Cardiology, Bronchopneumology, Bambino Gesù Hospital, Rome, Italy

    M. Cristina Digilio, Rossella Capolino, M. Beatrice Chiarini Testa, Andrea de Zorzi & Renato Cutrera

  2. IRCCS-CSS, San Giovanni Rotondo and CSS-Mendel Institute, Rome and Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy

    Anna Sarkozy, Giorgia Esposito & Bruno Dallapiccola

  3. Pediatric Cardiology, Department of Pediatrics, University La Sapienza, Rome, Italy

    Bruno Marino

Authors
  1. M. Cristina Digilio
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  2. Anna Sarkozy
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  3. Rossella Capolino
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  4. M. Beatrice Chiarini Testa
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  5. Giorgia Esposito
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  6. Andrea de Zorzi
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  7. Renato Cutrera
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  8. Bruno Marino
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  9. Bruno Dallapiccola
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Correspondence to M. Cristina Digilio.

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Digilio, M.C., Sarkozy, A., Capolino, R. et al. Costello syndrome: clinical diagnosis in the first year of life. Eur J Pediatr 167, 621–628 (2008). https://doi.org/10.1007/s00431-007-0558-0

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  • DOI: https://doi.org/10.1007/s00431-007-0558-0

Keywords

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