Facial Dysmorphism Across the Fetal Alcohol Spectrum

Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford St, London WC1N 1EH, UK. .
PEDIATRICS (Impact Factor: 5.47). 03/2013; 131(3):e779-88. DOI: 10.1542/peds.2012-1371
Source: PubMed


Classic facial characteristics of fetal alcohol syndrome (FAS) are shortened palpebral fissures, smooth philtrum, and thin upper vermillion. We aim to help pediatricians detect facial dysmorphism across the fetal alcohol spectrum, especially among nonsyndromal heavily exposed (HE) individuals without classic facial characteristics.
Of 192 Cape Coloured children recruited, 69 were born to women who reported abstaining from alcohol during pregnancy. According to multifaceted criteria, the remainder were allocated clinically to the FAS (n = 22), partial FAS (n = 26) or nonsyndromal HE (n = 75) categories. We used dense surface modeling and signature analyses of 3-dimensional facial photographs to determine agreement between clinical categorization and classifications induced from face shape alone, to visualize facial differences, and to consider predictive links between face shape and neurobehavior.
Face classification achieved significant agreement with clinical categories for discrimination of nonexposed from FAS alone (face: 0.97-1.00; profile: 0.92) or with the addition of partial FAS (face: 0.90; profile: 0.92). Visualizations of face signatures delineated dysmorphism across the fetal alcohol spectrum and in half of the nonsyndromal HE category face signature graphs detected facial characteristics consistent with prenatal alcohol exposure. This subgroup performed less well on IQ and learning tests than did nonsyndromal subjects without classic facial characteristics.
Heat maps and morphing visualizations of face signatures may help clinicians detect facial dysmorphism across the fetal alcohol spectrum. Face signature graphs show potential for identifying nonsyndromal heavily exposed children who lack the classic facial phenotype but have cognitive impairment.

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    • "igh as 2e5 / 100 for FASD in the developed world ( May et al . , 2014 ; May et al . , 2011 ; May et al . , 2009 ) , making it a leading cause of mental disability . Alcohol is a potent teratogen that can cross the placental barrier and lead to stunted growth ( Ulleland , 1972 ) , facial dys - morphia including smooth philtrum and thin upper lips ( Suttie et al . , 2013 ) , reduced brain volume ( X . Chen et al . , 2012 ; Lebel et al . , 2012 ) , deficits in various forms of learning and memory ( Coles et al . , 1991 ; Lewis et al . , 2015 ) as well as attentional and behavioural problems ( Brown et al . , 1991 ) and psychiatric ill - nesses like depression ( O ' Connor et al . , 2002 ; Roebuck et al ."
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    ABSTRACT: Neurodevelopmental disorders are a group of conditions that arises from impairments of the central nervous system during its development. The causes of the various disorders are heterogeneous and the symptoms likewise are multifarious. Most of these disorders currently have very little available treatment that is effective in combating the plethora of serious symptoms. Brain-derived neurotrophic factor (BDNF) is a fundamental neurotrophin with vital functions during brain development. Pre-clinical studies have shown that increasing BDNF signalling may be a potent way to prevent, arrest or even reverse abnormal neurodevelopmental events arising from a variety of genetic or environmental causes. However, many difficulties make BDNF problematic to administer in an efficient manner. The recent discovery of a small BDNF-mimetic, the naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF), may provide an avenue to allow efficient and safe activation of the BDNF pathway in tackling the symptoms of neurodevelopmental disorders. Here, evidence will be provided to support the potential of 7,8-DHF as a novel treatment for several neurodevelopmental disorders where the BDNF signalling pathway is implicated in the pathophysiology and where benefits are therefore most likely to be derived from its implementation. Copyright © 2015. Published by Elsevier Ltd.
    Neurochemistry International 07/2015; DOI:10.1016/j.neuint.2015.07.021 · 3.09 Impact Factor
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    • "These presentations are likely to be only a small proportion of eligible cases [5], and FAS is the only disorder that can be diagnosed in the absence of information on prenatal alcohol exposure due to the specificity of the three characteristic FAS facial anomalies. Although there is evidence of a correlation between the presence of characteristic FAS facial anomalies, prenatal alcohol exposure and brain dysfunction [18] which suggests that partial expressions of the FAS facial phenotype may be important risk factors for brain damage associated with prenatal alcohol exposure [51,52], there is insufficient evidence to justify relaxation of this referral criterion at this time. "
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    ABSTRACT: Background Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. Method An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed. Results Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the 16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities. Conclusion Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia.
    BMC Pediatrics 07/2014; 14(1):178. DOI:10.1186/1471-2431-14-178 · 1.93 Impact Factor
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    • "Instead, growth deficiencies, facial dysmorphology, and central nervous system dysfunctions are typically used to diagnose and categorize severity of exposure. Diagnosis is challenging as facial anomalies may be subtle or absent (Suttie et al., 2013). "
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    ABSTRACT: Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years) and controls (n = 16, 9.5–11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) thalamus, midbrain, and ventromedial frontal lobe, (2) superior cerebellum and inferior occipital lobe, (3) dorsolateral frontal cortex, and (4) precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions, underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.
    Clinical neuroimaging 04/2014; 5. DOI:10.1016/j.nicl.2014.04.001 · 2.53 Impact Factor
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