PMID- 22937012
OWN - NLM
STAT- MEDLINE
DCOM- 20130425
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Ethanol-induced face-brain dysmorphology patterns are correlative and 
      exposure-stage dependent.
PG  - e43067
LID - 10.1371/journal.pone.0043067 [doi]
LID - e43067
AB  - Prenatal ethanol exposure is the leading preventable cause of congenital mental 
      disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires 
      identification of a specific pattern of craniofacial dysmorphology, most 
      individuals with behavioral and neurological sequelae of heavy prenatal ethanol 
      exposure do not exhibit these defining facial characteristics. Here, a novel 
      integration of MRI and dense surface modeling-based shape analysis was applied to 
      characterize concurrent face-brain phenotypes in C57Bl/6J fetuses exposed to 
      ethanol on gestational day (GD)7 or GD8.5. The facial phenotype resulting from 
      ethanol exposure depended upon stage of insult and was predictive of unique 
      patterns of corresponding brain abnormalities. Ethanol exposure on GD7 produced a 
      constellation of dysmorphic facial features characteristic of human FAS, 
      including severe midfacial hypoplasia, shortening of the palpebral fissures, an 
      elongated upper lip, and deficient philtrum. In contrast, ethanol exposure on 
      GD8.5 caused mild midfacial hypoplasia and palpebral fissure shortening, a 
      shortened upper lip, and a preserved philtrum. These distinct, stage-specific 
      facial phenotypes were associated with unique volumetric and shape abnormalities 
      of the septal region, pituitary, and olfactory bulbs. By demonstrating that early 
      prenatal ethanol exposure can cause more than one temporally-specific pattern of 
      defects, these findings illustrate the need for an expansion of current 
      diagnostic criteria to better capture the full range of facial and brain 
      dysmorphology in fetal alcohol spectrum disorders.
FAU - Lipinski, Robert J
AU  - Lipinski RJ
AD  - The Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, 
      North Carolina, United States of America. lipinski@med.unc.edu
FAU - Hammond, Peter
AU  - Hammond P
FAU - O'Leary-Moore, Shonagh K
AU  - O'Leary-Moore SK
FAU - Ament, Jacob J
AU  - Ament JJ
FAU - Pecevich, Stephen J
AU  - Pecevich SJ
FAU - Jiang, Yi
AU  - Jiang Y
FAU - Budin, Francois
AU  - Budin F
FAU - Parnell, Scott E
AU  - Parnell SE
FAU - Suttie, Michael
AU  - Suttie M
FAU - Godin, Elizabeth A
AU  - Godin EA
FAU - Everson, Joshua L
AU  - Everson JL
FAU - Dehart, Deborah B
AU  - Dehart DB
FAU - Oguz, Ipek
AU  - Oguz I
FAU - Holloway, Hunter T
AU  - Holloway HT
FAU - Styner, Martin A
AU  - Styner MA
FAU - Johnson, G Allan
AU  - Johnson GA
FAU - Sulik, Kathleen K
AU  - Sulik KK
LA  - eng
GR  - T90 DE021986/DE/NIDCR NIH HHS/United States
GR  - P60 AA011605/AA/NIAAA NIH HHS/United States
GR  - U24 RR021760/RR/NCRR NIH HHS/United States
GR  - AA011605/AA/NIAAA NIH HHS/United States
GR  - P50 AA011605/AA/NIAAA NIH HHS/United States
GR  - P50 DE016215/DE/NIDCR NIH HHS/United States
GR  - P41 EB015897/EB/NIBIB NIH HHS/United States
GR  - DE-16215-05/DE/NIDCR NIH HHS/United States
GR  - AA007573/AA/NIAAA NIH HHS/United States
GR  - U24 CA092656/CA/NCI NIH HHS/United States
GR  - U01 AA017124/AA/NIAAA NIH HHS/United States
GR  - T32 AA007573/AA/NIAAA NIH HHS/United States
GR  - P30 HD003110/HD/NICHD NIH HHS/United States
GR  - T90DE021986-01/DE/NIDCR NIH HHS/United States
GR  - R00 AA018697/AA/NIAAA NIH HHS/United States
GR  - AA017124/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120822
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Brain/abnormalities/*embryology
MH  - Ethanol/*adverse effects
MH  - Face/abnormalities/*embryology
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/etiology/pathology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Pregnancy
PMC - PMC3425589
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/09/01 06:00
MHDA- 2013/04/26 06:00
PMCR- 2012/08/22
CRDT- 2012/09/01 06:00
PHST- 2012/04/25 00:00 [received]
PHST- 2012/07/16 00:00 [accepted]
PHST- 2012/09/01 06:00 [entrez]
PHST- 2012/09/01 06:00 [pubmed]
PHST- 2013/04/26 06:00 [medline]
PHST- 2012/08/22 00:00 [pmc-release]
AID - PONE-D-12-12392 [pii]
AID - 10.1371/journal.pone.0043067 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e43067. doi: 10.1371/journal.pone.0043067. Epub 2012 Aug 22.