1. 3D Facial Imaging Project
Tatiana Foroud
Elizabeth Moore
Richard Ward
Leah Wetherill
Li Shen
Jeffrey Rogers
Shiaofen Fang

2. Data Collection (3dMD only) (as of January 3, 2011)
Site
3D Images
(% of target)
DNA
San Diego
188 (125%)
157
UCLA
52 (104%) 80
Atlanta
116 (93%) 54
Ukraine
35 (37%)
0 (no approval)
Cape Town
224 (100%)
225*
Totals
599
516
* Also obtained 218 DNA samples from the mothers and 52 DNA samples from the father. RNA also collected at this site for the subject

3. DNA Saliva was obtained from US participants
DNA has been extracted
Will perform a GWAS at CIDR on 250 US participants
Data to be analyzed primarily for hypothesis generation
Insufficient power to support a GWAS for FAS

4. Pass Collaboration
Applied for and received approval to collect 3D images at 1 month and 12 months
Sample of 1200 will have longitudinal assessment
Training completed by Leah Wetherill and Mike Suttie earlier this month
Collection began last week

5. Pass Collaboration

6. Goal 1: Improve understanding of the dysmorphic features in FAS
Focused on site with the largest number of 3D images (South Africa)
FAS vs. controls
Alcohol exposed vs. controls
Goal is to delineate facial characteristics affected by alcohol exposure
Requires larger numbers in each group
Novel approaches to analyze single subjects being developed by Peter Hammond

7. Peter Hammond
Green: no difference between control and heavy exposed
Red: heavy alcohol exposed smaller than control
Blue: heavy alcohol exposed larger than control
Illustrates the power of a large number of controls
Focus future data collection to ensure large control groups of similar age and ethnicity
Peter Hammond

8. Comparison using data from South Africa
Goal 2: Enhance the capability of definitive diagnosis of fetal alcohol syndrome (FAS) and the broader spectrum of fetal alcohol spectrum disorders (FASD) at different stages of the lifespan
Comparison using data from South Africa
Each time point, age of sample is relatively homogenous
Time point 1 – average age 5 years
Time point 2 – average age 9 years
~90% of subjects seen at both time points
Data from 2 cameras

9. South Africa Longitudinal Sample
FAS
PFAS
Heavy exposure
Control
Total
Visit 1 17 24 47 57
145
Visit 2 26 83 87
220
Both 23 46
143
Both* 14 21 41 52
128
Controls
CIFASD FAS vs.
Heavy Prenatal Alcohol Exposure vs.
Controls

10. Anthropometric Measurements
7 widths:
MF: Minimal frontal (ft-ft)
BZ: Bizygoma (zy-zy
BT: Bitragal (t-t)
BG: Bigonial (go-go)
OC: Outer eye (ex-ex)
IC: Inner eye (en-en)
PF: Palpebral fiss (en-ex)
6 lengths:
NL: Nasal (n-sn)
NBL: Nasal bridge (n-prn)
PL: Philtrum (sn-ls)
LF: Lower face (sn-gn)
TFH: Total face (n-gn)
REL: Ear (sa-sba)
3 depths:
RUF: Upper face (t-n)
RMF: Mid face (t-sn)
RLF: Lower face (t-gn)

11. Discrimination
Used discriminant analyses to build models with the anthropometric measures
Compared 2 models
FAS vs. Control; Alcohol exposed vs. Control
Used stepwise models to add/remove variables
Difficult to compare variables in models since some measures correlated
Tried principal components with mixed results

12. Compare Measurements
Comparing means of anthropometric measurements at 2 time points between group definitions
Comparable to approach in Aim 1
Less focus on model building for diagnosis, more focus on understanding biological differences
Easier comparison to animal models
Consider greater subdivision of categories

13. Results Visit 1 (Ave Age 5)
FAS vs
FAS vs
PFAS vs
HE vs
group p
PFAS HE
Control
control
minimal frontal
0.0001
0.0208
0.0049
bizygomatic
0.0058
0.0002
bitragal
0.0004
0.0051
0.0005
bigonial
0.0579
0.0352
0.0098
0.0117
inner canthal
outer canthal
0.0009
palpebral fissure
0.0023
0.0003
upper facial depth
0.0076
mid facial depth
0.0037
lower facial depth
0.0025
0.017
0.0199
nose length
0.0112
0.0198
0.0018
0.0503
nasal bridge length
0.0006
0.0026
0.0089
philtrum length
lower facial height
total facial height
0.002
0.0303
ear length
0.0016
Age
0.0092
0.0036

14. Results Visit 2 (Ave Age 9)
FAS vs
FAS vs
PFAS vs
HE vs
group p
PFAS HE
Control
control
minimal frontal
0.0001
0.052
0.0008
0.0086
bizygomatic
0.0074
0.0098
0.0062
bitragal
0.0261
0.0987
0.0119
bigonial
0.0011
0.0443
0.0004
0.0002
inner canthal
outer canthal
0.0458
palpebral fissure
0.0158
0.0534
upper facial depth
0.034
0.0201
0.0037
mid facial depth
0.0218
0.0187
lower facial depth
0.0057
0.0277
nose length
0.0132
0.001
0.0078
0.0093
nasal bridge length
0.0003
0.0515
0.0238
0.0301
philtrum length
lower facial height
total facial height
0.0264
0.0177
ear length
Age
0.0085
0.0033
0.0016

15. Longitudinal Change FAS vs FAS vs PFAS vs HE vs group p PFAS HE
FAS vs
FAS vs
PFAS vs
HE vs
group p
PFAS HE
Control
control
minimal frontal
bizygomatic
0.0001
0.0009
0.0102
0.0018
0.0252
bitragal
0.027
0.015
bigonial
inner canthal
outer canthal
palpebral fissure
upper facial depth
0.008
0.0044
mid facial depth
0.0101
0.0420
0.0067
lower facial depth
0.0190
nose length
nasal bridge length
philtrum length
lower facial height
total facial height
ear length
0.041
0.059
0.037
Age
0.0085
0.0033
0.0016

16. Longitudinal Change (3 Group)
FAS vs. Deferred
FAS vs. Control
Deferred vs. Control
Group p
minimal frontal
0.4628
bizygomatic
0.0001
0.0003
bitragal
0.0008
0.0014
0.0046
bigonial
inner canthal
outer canthal
palpebral fissure
upper facial depth
0.0053
0.0037
mid facial depth
0.0024
0.0139
0.0036
lower facial depth
0.0009
0.0166
nose length
0.0083
0.0072
nasal bridge length
0.0312
0.0424
0.0542
philtrum length
lower facial height
total facial height
ear length
Age

18. Conclusions from Comparisons
Many variables differ among the groups at each time point
Few variables (bizygomatic width, facial depths) have significantly different rates of change across the two time points
Relatively constant growth rate during this period

19. Replication Growing sample of longitudinal data in San Diego
42 individuals in SD with 2 longitudinal images
Growing number are being seen in the next year for a longitudinal visit

20. Plans for the Next Year Collect images at 3 US sites
Small study in Minneapolis (increase # of US FAS)
Collect images in South Africa
Both infants and adolescents
Aim 1 – Delineate facial differences in alcohol exposure
Human only studies
Sample size to compare South Africa and African Americans
More comparison with animal models
Aim 2- Longitudinal analyses
Currently cross camera; will start within camera

22. South Africa FAS Classification
Short palpebral fissures, thin upper lip, flat/smooth philtrum, small OFC, growth retardation
PFAS
2 of 3 facial + small OFC + growth retardation
Heavy exposure
Mother drank ≥ 1 oz pure alcohol/day or 4 binges (≥ 4 drinks or 2 oz alcohol/occasion)