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PLoS One. 2012;7(8):e43067. doi: 10.1371/journal.pone.0043067. Epub 2012 Aug 22. Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. Lipinski RJ1, Hammond P, O'Leary-Moore SK, Ament JJ, Pecevich SJ, Jiang Y, Budin F, Parnell SE, Suttie M, Godin EA, Everson JL, Dehart DB, Oguz I, Holloway HT, Styner MA, Johnson GA, Sulik KK. Author information

Abstract 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. PMID 22937012

Abnormal Cortical Thickness Alterations in Fetal Alcohol Spectrum Disorders and Their Relationships with Facial Dysmorphology

Yang Y, Roussotte F, Kan E, Sulik KK, Mattson SN, Riley EP, Jones KL, Adnams CM, May PA, O'Connor MJ, Narr KL, Sowell ER.Cereb Cortex. 2011 Jul 28. [Epub ahead of print]

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Magnetic resonance-based imaging in animal models of fetal alcohol spectrum disorder

O'Leary-Moore SK, Parnell SE, Lipinski RJ, Sulik KK.Neuropsychol Rev. 2011 Jun;21(2):167-85. Epub 2011 Mar 29.

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Zhang C, Turton QM, Mackinnon S, Sulik KK, Cole GJ.Birth Defects Res A Clin Mol Teratol. 2011 Mar;91(3):129-41. doi: 10.1002/bdra.20766. Epub 2011 Feb 9.

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Parnell SE, Sulik KK, Dehart DB, Chen SY.Alcohol. 2010 Nov-Dec;44(7-8):699-705. Epub 2010 Jun 18.

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===Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing.Bolon B, Garman RH, Gundersen HJ, Allan Johnson G, Kaufmann W, Krinke G, Little PB, Makris SL, Mellon RD, Sulik KK, Jensen K.Toxicol Pathol. 2011 Jan;39(1):289-93. Epub 2010 Nov 12.PMID: 21075916 [PubMed - indexed for MEDLINE]Related citations

Ventromedian forebrain dysgenesis follows early prenatal ethanol exposure in mice

Godin EA, Dehart DB, Parnell SE, O'Leary-Moore SK, Sulik KK.Neurotoxicol Teratol. 2011 Mar-Apr;33(2):231-9. Epub 2010 Nov 11.

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A mouse strain where basal connective tissue growth factor gene expression can be switched from low to high

Doherty HE, Kim HS, Hiller S, Sulik KK, Maeda N.PLoS One. 2010 Sep 22;5(9):e12909.

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