PMID- 24668879
OWN - NLM
STAT- MEDLINE
DCOM- 20150113
LR  - 20211021
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 164A
IP  - 6
DP  - 2014 Jun
TI  - Craniofacial and dental development in Costello syndrome.
PG  - 1425-30
LID - 10.1002/ajmg.a.36475 [doi]
AB  - 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.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Goodwin, Alice F
AU  - Goodwin AF
AD  - Program in Craniofacial and Mesenchymal Biology, and Division of Craniofacial 
      Anomalies, Department of Orofacial Sciences, University of California San 
      Francisco, San Francisco, California.
FAU - Oberoi, Snehlata
AU  - Oberoi S
FAU - Landan, Maya
AU  - Landan M
FAU - Charles, Cyril
AU  - Charles C
FAU - Massie, Jessica C
AU  - Massie JC
FAU - Fairley, Cecilia
AU  - Fairley C
FAU - Rauen, Katherine A
AU  - Rauen KA
FAU - Klein, Ophir D
AU  - Klein OD
LA  - eng
GR  - F30-DE022205/DE/NIDCR NIH HHS/United States
GR  - R01-AR062165/AR/NIAMS NIH HHS/United States
GR  - R01 DE021420/DE/NIDCR NIH HHS/United States
GR  - R01-DE021420/DE/NIDCR NIH HHS/United States
GR  - F30 DE022205/DE/NIDCR NIH HHS/United States
GR  - R01 AR062165/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140325
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - Cardiofaciocutaneous syndrome
SB  - IM
MH  - Abnormalities, Multiple/embryology/genetics
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Costello Syndrome/*genetics
MH  - Craniofacial Abnormalities/*embryology/*genetics
MH  - Dental Enamel Hypoplasia/embryology/genetics
MH  - Ectodermal Dysplasia/embryology/genetics
MH  - Facies
MH  - Failure to Thrive/embryology/genetics
MH  - Female
MH  - Gingival Hyperplasia/embryology/genetics
MH  - Heart Defects, Congenital/embryology/genetics
MH  - Humans
MH  - MAP Kinase Signaling System/*genetics
MH  - Male
MH  - Malocclusion/embryology/genetics
MH  - Mitogen-Activated Protein Kinases/genetics
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Proto-Oncogene Proteins p21(ras)/*genetics
MH  - Tooth/embryology
MH  - Tooth Abnormalities/embryology/genetics
MH  - Young Adult
PMC - PMC4115793
MID - NIHMS604109
OTO - NOTNLM
OT  - CS
OT  - Costello syndrome
OT  - MAPK pathway
OT  - RASopathy
OT  - Ras
OT  - craniofacial development
OT  - enamel
OT  - gingival hyperplasia
OT  - malocclusion
OT  - occlusion
OT  - receptor tyrosine kinase
OT  - signal transduction
OT  - tooth development
COIS- Conflict of interest: none.
EDAT- 2014/03/29 06:00
MHDA- 2015/01/15 06:00
PMCR- 2015/06/01
CRDT- 2014/03/27 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2013/12/31 00:00 [accepted]
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/01/15 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - 10.1002/ajmg.a.36475 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2014 Jun;164A(6):1425-30. doi: 10.1002/ajmg.a.36475. Epub 2014 
      Mar 25.