1. Craniofacial Dysmorphism & Fetal Alcohol Exposure
Tatiana Foroud and Peter Hammond (PIs)
Leah Wetherill, Mike Suttie

2. Update on Image Collection
Site
As of Jan 2013 Images
(# subjects)1
As of April 2014 Images
As of February 2015 Images
San Diego
239 (215)
349 (273)
416 (312)
UCLA/USC
52 (52)
75 (67)
104 (88)
Atlanta
147 (147)
203 (203)
248 (248)
Minneapolis
50 (50)
174 (139)
238 (236)
Ukraine
47 (34)
159 (95)
South Africa (Jacobson)
223 (223)
517 (312)
South Africa (May)
37 (37)
South Africa (PASS)
1,738 (1,221)
2,361 (1,221)
Totals
2,533 (1,979)
3,763 (2,286)
4,080 (2,549)
1 Some subjects have longitudinal image collection

3. Racial Distribution of Subjects
Alcohol Exposure

4. Update on Saliva Collection
Site
As of Jan 2013
As of April 2014
As of Feb 2015
San Diego
131
287
421 (246)
UCLA/USC 45
110
159 (108)
Atlanta 28
194
353 (227)
Minneapolis
170
349 (194)
Ukraine 01
South Africa (Jacobson)
225
South Africa (PASS)
1 Collection of samples done as part of parent protocol

5. Use of DNA for Research GWAS completed in 240 individuals
700,000 SNPs genotyped (Illumina OmniExpress)
Variable alcohol exposure and phenotype
Data used for candidate gene studies
Genotype x alcohol interaction
Developmental Project completing GWAS in another 327 subjects
2 million SNPs being genotyped (Illumina MEGA)

6. FYN
philtrum
pc2
philtrum
pc9
executive
function
CC mid
posterior

7. New Directions
Develop multidimensional phenotypes that can be used for analysis
Focus of the RSA symposium in June 2015

8. Analysis Objectives
Develop a screening tool that would utilize the data from the 3D facial images and could be widely used to accurately identify individuals with a high likelihood of alcohol exposure
Recruit & analyze facial imaging data from very young populations to develop a screening tool that accurately identifies high risk individuals for future intervention
Combine face images, neurobehavioral data & brain images to identify common pathways & improve diagnosis of prenatal alcohol exposure
Extend existing and develop novel techniques and associated software to cope with demands of larger datasets and more diverse comparison of controls, alcohol exposed and other developmentally delayed subjects while accommodating multiple anatomical images per subject
Extend preliminary genetic studies through collection of DNA samples for new subjects and focused analysis to replicate candidate genes identified in basic science components.

9. COMPLETED TATIANA Analysis Objectives
Develop a screening tool that would utilize the data from the 3D facial images and could be widely used to accurately identify individuals with a high likelihood of alcohol exposure
Recruit & analyze facial imaging data from very young populations to develop a screening tool that accurately identifies high risk individuals for future intervention
Combine face images, neurobehavioral data & brain images to identify common pathways & improve diagnosis of prenatal alcohol exposure
Extend existing and develop novel techniques and associated software to cope with demands of larger datasets and more diverse comparison of controls, alcohol exposed and other developmentally delayed subjects while accommodating multiple anatomical images per subject
Extend preliminary genetic studies through collection of DNA samples for new subjects and focused analysis to replicate candidate genes identified in basic science components.
COMPLETED
TATIANA

10. Face–cognitive impairment in exposed children not diagnosable as FAS/PFASHE
(Suttie et al, Pediatrics, 2013)

11. HE1FAS-like HE2 CTRL like
Face–cognitive impairment in exposed children not diagnosable as FAS/PFAS
(Suttie et al, Pediatrics, 2013)
HE1
FAS
WISC IQ
65.5
65.4
CVLT-C1
40.0
42.7
CVLT-C2
84.3
88.5
HE2 HC
WISC IQ
73.3
CVLT-C1
47.3
45.8
CVLT-C2
93.7
93.2
HE1FAS-like
HE2
CTRL
like

12. N=192 (JACOBSEN) Cape- Coloured N=227 (CIFASD) Caucasian
Recapitulate Pediatrics paper analysis
from Cape Coloured to CIFASD Caucasian
Suttie et al (2013) Pediatrics, 131 (3), e779-e788
HC = 69
FAS = 22
HE = 75
HC = 69
FAS/PFAS = 48
HE = 75
N=192
(JACOBSEN)
5yr-15 yr
Cape-
Coloured
HC = 121
FAS = 34
HE = 74
N=227
(CIFASD)
5yr-15+ yr
Caucasian

13. Does HE face predict cognitive impairment ?
CAPE
CAUCASIAN + HISPANIC
FAS
HE FAS-like
HE control-like

14. Does HE face predict cognitive impairment ?
CAPE
CAUCASIAN ONLY
FAS
HE FAS-like
HE control-like

15. Probability of agreeing with clinical diagnosis of pair of faces – 1 HC & 1 FAS
HC vs FAS
CAPE
CAUCASIAN CM
LDA
SVM
PROFILE
0.97
0.83
0.85
0.88
FACE
0.95
0.87
MALAR
0.79
0.80
NOSE
0.90
0.92
0.91
0.94
PHILTRUM
0.72
0.78
0.86
Cape FAS
Caucasian FAS

16. Facial growth reduction due to prenatal alcohol exposure (PAE): Cape >> Caucasian

17. Homogeneity of PAE induced facial dysmorphism : Cape FAS > Caucasian FAS

18. Mean curvature at point on face surface (not normalised)
“concave”
“flat”
“convex”

19. Groove & curl at point on philtrum
subnasale
lip centre
CURL
GROOVE

20. The philtrum: the curl and groove of it
low groove/high curl
high groove/high curl/
CURL
low groove/low curl
high groove/low curl
GROOVE

21. Variation in philtrum groove & pillar definition).
Variation in philtrum groove & pillar definition

22. Mean groove & philtral pillar definition :
Cape Control << Caucasian Control
CONTROL
shape
curl
groove C A P E C A U

23. PAE induced effect on philtrum groove/pillars:
Cape FAS << Caucasian FAS
CONTROL
FAS
shape
curl
groove
shape
curl
groove C A P E C A U

24. Cape vs Caucasian differences explaining discrimination variation with location
FAS facial growth delay: Cape > Caucasian
FAS facial dysmorphism: Cape more homogeneous
HC upper philtrum smoothness: Cape > Caucasian
FAS philtrum smoothness: Caucasian > Cape (?)
FAS malar region effect: Cape > Caucasian
CIFASD Hispanic & African-American analysis to be completed

25. Measuring volume of philtral groove
facet on
philtrum
facet on
lid
positive
voxel
projection
plane
negative
voxel
curl

26. PHILTRUM VOLUME vs AGE: Caucasian controls

27. Tentative Measure of Philtrum Smoothness “Philtrum Groove Index”
subnasale
lip centre
Philtrum Groove Index = Philtrum Volume / Philtrum Length
corresponds to average cross sectional area

28. CAUCASIAN:Philtrum Groove Index vs PFL (HC=45; FAS=15; HE=40)
* Pearson coeff 0.315, p=0.035 for controls

29. CAPE:Philtrum Groove Index vs PFL (HC= 64; FAS=17 )
* Pearson coeff 0.356, p < 0.01 for controls

30. Face screening tool
TOOL

31. 3dMD camera vs Canfield H1 hand-held

32. 3dMD CCA386
H1 CCA386

33. H1 CCA386
3DMD CCA386
H1 vs 3DMD means
H1 MEAN SIG
3DMD MEAN SIG

34. Philtrum Volume 3dMD vs H1

35. Mean FAS (N=12) vs Mean HC (N=21) Face & CC and Philtrum & CC

36. Profile+CC closest mean classification
Vs Wiscfullscalecomp
MEAN HC
MEAN FAS

37. Correlation of Philtrum Groove Index & Corpus Callosum PCA Modes
Pearson
0.381**
0.363*
0.349*
Sig (2-tailed)
0.010
0.014
0.019
Mode 9
1% variance
Mode 29
0.06% variance
Mode 2
14.2% variance

38. Papers Cape – Caucasian differences - DRAFT
Screening tool – DRAFT USER DOC
Prenatal with PASS – CIFASD report close to draft
Face-cognition-brain – DRAFT end of April

39. CIFASD IV – Future Face Work
Automated Landmarking (using 2D and 3D)
Automated Analysis with Cloud based models
Tablet/Smartphone 2D and 3D image capture
Selected PCA modes per individual for accurate face synthesis in dense surface models
Non-Caucasian and Ad-mix populations

41. Analysis of 21 3D U/S : Alison Noble (Oxford)
Tom Rackham extracted profiles
Shape analysis – PC1
PC1 correlates with Trimester 2 drinking (DM-Stat/PASS)
Not adjusted for Gest Age
Adjusted for Gest Age
drinks per drinking day by trimester and up to date of measurement
r=0.42, p=0.0597
r=0.42, p=0.0667
binge vs. no binge by trimester and up to date of measurement (t-test)
p=0.031*
drinks per drinking week by trimester and up to date of measurement
r=0.52, p=0.017*
r=0.52, p=0.019*