1. Dysmorphology Core: Progress Report February 1, 2011
Kenneth Lyons Jones, H. Eugene Hoyme, Luther K. Robinson, Melanie Manning, Miguel del Campo, Christina D. Chambers

2. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineate the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
To better understand the extent to which structural features of FASD are related to specific defects in brain development.

3. Criteria for FASD Classification
1) Growth deficiency defined as pre- or postnatal weight or length
≤10th% for sex and age adjusted for prematurity if <12 months. Or
microcephaly defined as ≤10th% for sex and age adjusted for
prematurity if <12 months
2) At least two of the following facial features:
- Short palpebral fissures (≤10th% for sex and age adjusted for
prematurity if <12 months.)
- Philtrum smoothness (4 or 5 using Astley/Clarren Lip Philtrum guide)
- Smooth vermilion (4 or 5 using Astley/Clarren Lip Philtrum guide)
NO FAS:
1) Only growth deficiency
2) Only microcephaly
3) None of the three cardinal facial features compatible with FAS

4. Criteria for FASD Classification
DEFERRED:
1) At least one facial feature OR
2) Microcephaly (OFC ≤10th%) AND growth deficiency defined as
weight and/or length ≤10th% OR
3) Microcephaly and at least one of the following features: ptosis,
railroad track ears, hockey stick palmar crease, other palmar
crease abnormalities, joint contractures, decreased
pronation/supination at the elbows, hirsuitism, heart murmur OR
4) Growth deficiency defined as weight
and/or length ≤10th% AND at least one of the following features:
ptosis, railroad track ears,hockey stick palmar crease, other palmar
crease abnormalities, joint contractures, decreased
pronation/supination at th elbows, hirsuitism, heart murmur.

5. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineate the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
To better understand the extent to which structural features of FASD are related to specific defects in brain development.

10. Table 5: Number of Exams Completed (by Examiner and Site) in the Yr 2010

12. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineate the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
To better understand the extent to which structural features of FASD are related to specific defects in brain development.

13. Fetal Alcohol Spectrum Disorders: Establishing the broad range of structural defects. (Specific Aim 2)
We examined 831 children from the CIFASD using a structured protocol for diagnosis of FASD using the cardinal facial and growth features, and assessment of additional structural defects thought to occur more often in children with prenatal alcohol exposure.
Subjects were classified as FAS, Deferred or No FAS.
Groups were compared on prevalence of additional features and number of additional features observed, stratified by diagnostic category, sex, race and age.
Prevalence of most additional features was greatest among subjects with FAS and least among No FAS.
A higher frequency of additional features was observed among FAS and Deferred subjects >12 years of age than among those under 12.
In children in the FAS and Deferred groups, significantly more children of white race had two or more additional features than Cape Colored
Jones KL, Hoyme HE, Robinson LK, del Campo M, Manning MA, Prewitt LM, Chambers CD Amer J Med Genet 152A:

18. Pearson chi-square or Fisher’s Exact Test

19. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineated the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
To better understand the extent to which structural features of FASD are related to specific defects in brain development.

20. Neurobehavioral Profile (Specific Aim 2)
A neuropsychological battery was used to determine a profile that could be used to accurately identify children affected by prenatal exposure to alcohol.
The data suggest that children with FAS based on the physical examination are similar based on a specific set of neuropsychological tests to children prenatally exposed to alcohol who do not fulfill criteria for FAS based on the physical examination.
Documentation of a behavioral phenotype may allow identification that a child’s neurobehavioral abnormalities even without the characteristic physical phenotype of FAS is the result of prenatal alcohol exposure
Provides a better understanding of the broad spectrum of abnormalities associated with prenatal exposure to alcohol.
Mattson SN,Roesch SC, Fagerlund A, Autti-Ramo I, Jones KL, May PA, Adnams CM, Konovalova V, Riley EP, and the CIFASD 2010 Toward a neurobehavioral profile of fetal alcohol spectrum disorders Alcohol Clin Exp Res 34:

21. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineated the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
5. To better understand the extent to which structural features of FASD are related to specific defects in brain development.

22. Correlation of features identified on physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects. (Specific Aim 4)
A study has been completed correlating maternal drinking during pregnancy with prenatal ultrasound findings.
Differences in selected somatic and brain measurements
between alcohol - exposed and comparison fetuses have been
demonstrated.
Kfir M, Yevtushok L, Onishchenko S, Wertelecki W, Bakhireva L, Chambers CD, Jones KL, Hull AD 2009 Can prenatal ultrasound detect the effects of in utero alcohol exposure? – A pilot study. Ultrasound Obstet Gynecol. 33:
A study has been completed examining the ability to recognize FAS from 3D facial imaging. The results demonstrate the use of computer algorithms to detect facial features that can discriminate FAS and control facies.
Klingenberg CP, Wetherill L, Rogers J, Moore E, Ward R, Autti-Rämö I, Fagerlund A, Jacobson SW, Robinson LK, Hoyme HE, Mattson SN, Li TK, Riley EP, Foroud T; CIFASD Consortium Prenatal alcohol exposure alters the pattern of facial asymmetry Alcohol 44(7-8):

23. Specific Aims
To assure consistency as well as accuracy in recognition of FASD at all CIFASD project sites where children are being evaluated.
To delineated the full range of structural anomalies in children prenatally exposed to alcohol in order to determine the boundaries that encompass FASD in prospective as well as retrospective studies in the Consortium.
3. To identify specific structural defects or clusters of features that are predictive of or correlated with deficits in neurobehavioral development across development ages spanning from infancy to adolescence.
4. To correlate the specific structural features or clusters of features identified on the CIFASD standard physical examination with alternative or complimentary diagnostic methods that are being tested in other CIFASD projects.
5. To better understand the extent to which structural features of FASD are related to specific defects in brain development.

24. Relationship of structural features of FASD to specific defects in brain development. (Specific Aim 5)
Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders.
Smaller palpebral fissures were significantly associated with
reduced volumes in the ventral diencephalon bilaterally, and
that philtral smoothness predicted smaller volumes in the left
pallidum, as well as in the thalamus bilaterally
Roussotte, F, Sulik KK, Mattson S, Riley P, Jones K, Adnams C, May P, O’Connor M, Narr K, Sowell E and the CIFASD. Human Brain Mapping. In press

25. Plans for Next Year:
We will continue to see children ascertained at all CIFASD sites throughout the world.
Determine if there is a common pattern of structural brain defects, consistent neurobehavioral abnormalities and typical findings on 3-D imaging of the face in children categorized by the dysmorphology core as FAS
- # of children with all four modalities completed: 7
- # of children with 3 of the four completed: 35
Analyze the data we have with physical exams, neurobehavioral evaluations and data regarding alcohol exposure to determine the broad spectrum of defects associated with prenatal alcohol exposure

26. Some Alcohol-Related Physical Features or Neurobehavioral Impairment
This category will be an option for final classification of subjects who do not meet the criteria for FAS after all relevant information has been gathered, including neurobehavioral testing but who have any one of the following:
1) One or more of the characteristic cardinal facial features
2) Additional non-cardinal features of FAS
3) Growth deficiency defined as height or weight or OFC ≤10%
4) Neurobehavioral impairment
- Subjects with these features who do not meet the criteria for FAS will be placed in this category
-Therefore Deferred children who do not subsequently become classified as FAS will ultimately be placed in this group
- This is the group of children from which the full range of FASD can be determined

27. Categories to be used as starting point for describing range and prevalence of features
Group I - FAS
A) FAS based on examination alone
B) Initially deferred but reclassified as FAS based on
neurobehavioral evaluation
Group II - Alcohol-Related Features and/or Neurobehavioral Impairment
A) Initially deferred but normal neurobehavioral evaluation
B) Normal physical exam but neurobehavioral impairment
Group III - No FAS
A) No physical features and normal neurobehavioral performance

28. Maternal Alcohol Exposure Levels as a Second Method of Grouping
Confirmed Heavy Prenatal Alcohol Exposure = Exposed
Confirmed minimal or No Prenatal Alcohol Exposure = Unexposed
Unknown Alcohol Exposure = Unknown
These categories of exposure will be used to describe the prevalence of physical features according to quantity, frequency, timing and pattern of alcohol use, taking into consideration other potential confounders such as tobacco use or pregnancy history.

29. Prevalence of Physical Features and Neurobehavioral
Impairment According to Alcohol Exposure Category
Prospective Subjects
Retrospective Subjects
Total of Subjects
Grp I II
III
Total
Expose n
(%) N
100%
Not
Exposed
Known
Grp I=FAS; Grp II= Alcohol related features and/or Neurobehavioral impairment; Grp III=No FAS