Craniofacial and dental development in Costello syndrome

Alice F. Goodwin, Snehlata Oberoi, Maya Landan, Cyril Charles, Jessica C. Massie, Cecilia Fairley, Katherine A Rauen, Ophir D. Klein

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n=41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development.

Original languageEnglish (US)
Pages (from-to)1425-1430
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number6
StatePublished - 2014
Externally publishedYes


  • Costello syndrome
  • Craniofacial development
  • CS
  • Enamel
  • Gingival hyperplasia
  • Malocclusion
  • MAPK pathway
  • Occlusion
  • Ras
  • RASopathy
  • Receptor tyrosine kinase
  • Signal transduction
  • Tooth development

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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