Facial Dysmorphism Across the Fetal Alcohol Spectrum

Suttie, Michael; Foroud, Tatiana; Wetherill, Leah; Jacobson, Joseph L.; Molteno, Christopher D.; Meintjes, Ernesta M.; Hoyme, H. Eugene; Khaole, Nathaniel; Robinson, Luther K.; Riley, Edward P.; Jacobson, Sandra W.; Hammond, Peter

doi:10.1542/peds.2012-1371

Cited by 115 publications

(131 citation statements)

References 42 publications

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“…Of particular note, ND-PAE criteria failed to reliably identify the presence of partial FAS and FAS, which diagnoses incorporate cardinal facial features that are highly specific to the effects of prenatal alcohol exposure. 20 Although the impairment cut-off for ND-PAE may be conservative in this study, the low sensitivity of the DSM-5 criteria is in part rooted in its organizational structure. The DSM-5 criteria as is imply a shared neurobehavioral profile among patients affected by ND-PAE.…”

Section: Discussionmentioning

confidence: 88%

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Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

2017

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Section: Discussionmentioning

confidence: 88%

“…20 These facial characteristics include short palpebral fissures, smooth philtrum and thin upper lip, and were measured in consort with the Canadian guidelines 8 and the 4-digit code. 7 Given the specificity of these facial features to prenatal alcohol effects, classification of ND-PAE should be correlated to FAS and partial FAS.…”

mentioning

confidence: 99%

Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

2017

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“…Facial dysmorphology was characterized by dense surface modeling of 3-dimensional images (21). Principal components (PCs) were derived by reducing 28,000 data points using a mathematical representation resulting in 10 facial, 10 philtral, and 10 profile PCs.…”

Section: Association Analysis In the Collaborative Initiative On Fetamentioning

confidence: 99%

L1 coupling to ankyrin and the spectrin‐actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis

et al. 2018

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Ethanol causes fetal alcohol spectrum disorders (FASDs) partly by inhibiting cell adhesion mediated by the L1 neural cell adhesion molecule. Ethanol interacts with an alcohol binding pocket in the L1 extracellular domain (ECD), and dephosphorylation of S1248 in the L1 cytoplasmic domain (CD) renders L1 adhesion insensitive to inhibition by ethanol (L1 insensitive). The mechanism underlying this inside-out signaling is unknown. Here we show that phosphorylation of the human L1-CD at S1152, Y1176, S1181, and S1248 renders L1 sensitive to ethanol by promoting L1 coupling with ankyrin-G and the spectrin-actin cytoskeleton. Knockdown of ankyrin-G or L1 mutations that uncouple L1 from ankyrin reduce L1 sensitivity to ethanol, but not methanol, consistent with a small conformational change in the extracellular alcohol binding pocket. Phosphorylation of Y1176 and ankyrin-G coupling with L1 are higher in NIH/3T3 clonal cell lines in which ethanol inhibits L1 adhesion than in ethanol-resistant NIH/3T3 clonal cell lines. Similarly, phosphorylation of Y1176 is higher in C57BL/6J mice that are sensitive to ethanol teratogenesis than in ethanol resistant C57BL/6N mice. Finally, polymorphisms in genes that encode ankyrin-G and p90rsk, a kinase that phosphorylates S1152, are linked to facial dysmorphology in children with heavy prenatal ethanol exposure. These findings indicate that genes that regulate L1 coupling to ankyrin may influence susceptibility to FASD.-Dou, X., Menkari, C., Mitsuyama, R., Foroud, T., Wetherill, L., Hammond, P., Suttie, M., Chen, X., Chen, S.-Y., Charness, M. E., Collaborative Initiative on Fetal Alcohol Spectrum Disorders. L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis. FASEB J. 32, 1364FASEB J. 32, -1374FASEB J. 32, (2018. www.fasebj.orgFetal alcohol spectrum disorder (FASD) is the most common preventable cause of intellectual disability (1, 2). At the most severe end of the spectrum are children with fetal alcohol syndrome (FAS), a disorder marked by typical facial dysmorphology, pre-and/or postnatal growth deficiency, neurobehavioral impairment, and structural or functional brain abnormalities. The facial dysmorphology of FAS arises from alcohol exposure during gastrulation, but ethanol can disrupt brain development throughout gestation (3). Consequently, many children with prenatal alcohol exposure and normal facial morphology still demonstrate cognitive, behavioral, and social impairment (2). Although FASD is preventable, fetal alcohol exposure still occurs frequently before pregnancy recognition and often later in gestation, despite the known risks (4).Genetic factors modify the risk of FASD (5). Ethanol teratogenicity differs markedly in genetically related animal strains (6), and human monozygotic twins demonstrate higher concordance for FAS than dizygotic twins (7).

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“…2, 46 Borenstein et al 47 reported that using 3D volumes of the fetal head in order to define the relative position of the maxilla and mandible in fetuses with trisomy 18 compared to chromosomally normal individuals improves the detection rate to 92%. Although fetal alcohol syndrome refers to facial dysmorphisms, 48 research has not reported variations in fetal facial movements. Given the changes in the facial anatomy, there is the potential to establish not only the dysmorphism by analyzing the fetal facial anatomy but also variations in movements.…”

Section: Use Of Ultrasound Images Can We Use Fetal Facial Movements Fmentioning

confidence: 99%

What the Fetal Face can tell Us: A Discussion of the Evidence, Implications and Potential for Further Research

Reissland

2014

Donald School Journal of Ultrasound in Obstetrics and Gynecology

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This paper reviews findings in fetal development research using two-dimensional and four-dimensional ultrasound imaging and how these techniques have been applied to increase understanding of the fetus. The limitations of differences in language and methods used to code and score images between research groups will also be explored, reaching the conclusion that a reliable coding scheme for fetal facial movements is essential. Furthermore, applications of the new technology studies of bonding between parent and fetus, cross-cultural research on fetal facial development and medical applications are discussed.

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Facial Dysmorphism Across the Fetal Alcohol Spectrum

Cited by 115 publications

References 42 publications

Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study

L1 coupling to ankyrin and the spectrin‐actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis

What the Fetal Face can tell Us: A Discussion of the Evidence, Implications and Potential for Further Research

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