Characterizing the Phenotype of Williams- Beuren S yndrome in - PowerPoint PPT Presentation

1 Characterizing the Phenotype of Williams- Beuren S yndrome in Diverse Populations Katherine Pardo 1,2 , Paul Kruszka, M.D. 2 , Maximilian Muenke, M.D. 2 University of Virginia 1 ; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health 2

2 Atlas of Human Malformation Syndromes in Diverse Populations  Response to many non-Caucasian populations having limited access to geneticists and are underrepresented in medical and genetic research.  Addressing the notion that discrepancies in racial and ethnic background have posed a widespread challenge to phenotypic diagnosis.  Will contain photographs and molecular diagnoses of individuals from diverse geographic locations.  Will serve as a tool for clinicians in diagnosing syndromic disorders by promoting the association of congenital malformations with syndromes.

3 Obj ective To characterize the phenotype of Williams-Beuren S yndrome in underrepresented non-Caucasian populations in order to enhance the ability to clinically diagnose Williams-Beuren S yndrome across diverse populations.

4 Introduction • Williams-Beuren S yndrome: a multisystem disorder resulting from a chromosomal abnormality.  Often determined to be de novo 1. and occasionally hereditary  Dist inct ive facies  Intellectual disability  S upravalvular aortic stenosis  Pulmonary arterial stenoses  Hypercalcemia  Dental malformation  Unusually outgoing and trusting personality Figure 1. Chinese female with 1. Yau EK, Lo IF, Lam ST. Williams-Beuren syndrome in the Hong Kong Chinese positive clinical diagnosis. population: retrospective study. Hong Kong Med J. 2004 Feb;10(1):22-7. PubMed PMID: 14967851.

5 Procedure and Methods  41 patients have been clinically diagnosed with Williams-Beuren S yndrome and characterized by specific facial and gestalt phenotype.  Facial Dysmorphology Novel Analysis, (FNDA) analysis using Face2Gene Technology served as exploratory tool for future diagnostic uses and an obj ective facial characterization instrument.

6 Facial Dysmorphology Novel Analysis, (FDNA): Face2Gene 1. 1. Yau EK, Lo IF, Lam ST. Williams-Beuren syndrome in the Hong Kong Chinese population: retrospective study. Hong Kong Med J. 2004 Feb;10(1):22-7. PubMed PMID: 14967851.

7 Face2Gene  Face2Gene uses Bayesian net works t o assess t he probabilit y of having a syndrome.  Gestalt: heat maps display the most distinguishable facial regions  Red: strong similarity to a syndrome  Blue: absence of similarity to a syndrome  Feature: facial proportions are obtained and compared against a continually developing database.

8 Results • Underrepresentation of medical literature on individuals from diverse populations.

Results 9

10 Results S ensitivity= Number of True Positives X 100 _______________________________________________________________________________________________________ Number of True Positives + False Negatives

11 Discussion  Williams-Beuren S yndrome lacks definition in underprivileged non-Caucasian populations due to the small amount of reported cases.  The distinct ive facies characterizing Williams- Beuren S yndrome in Caucasians are consistent with found in non-Caucasian individuals.  Face2Gene should only be used to support diagnostic confirmation only and should not be used as a primary diagnostic method.

12 Conclusion  Williams-Beuren S yndrome in individuals from diverse populations is under-represent ed in the medical literature.  The considerable precision of FDNA analysis using Face2Gene technology and its efficient improvement mechanism is indicative of its potential as a valuable resource to clinicians.  This research will potentially enhance the quality and accuracy of diagnosing Williams-Beuren S yndrome in individuals.

13 Future Directions • Charact erizing Williams-Beuren S yndrome in diverse populat ions from Asia, S ub-S aharan Africa, Lat in American, and t he Middle East . • Adding a cont rol sample consist ing of individuals wit h syndromic diagnoses not including Williams-Beuren S yndrome t o furt her st at ist ical analysis. • Quant ifying observer variat ion t hrough blind t est ing of unrelat ed clinicians. • Test ing t he accuracy and precision of FDNA analysis using Face2Gene t echnology on individuals wit h a wide variet y of syndromes.

14 Acknowledgements Many t hanks go t o t he generous donors t o t he College S cience S cholars program who make t hese summer research awards possible: Charles Henry Leach, II, Foundat ion, Mr. S t eve Van Besien; Ent igence Corporat ion; Lois A. Fit t on & W. Christ opher Draper, Jr.; S haron B. Parent e & John W. Risner; The Jefferson Trust ; Robert At kinson; Lowe Family; Dean’s discret ionary gift s. I sincerely t hank Dr. Muenke and Dr. Kruszka for providing me wit h t he life-changing opport unit y of researching at t he Nat ional Inst it ut es of Healt h, and Professor S chmidt , Professor Epst ein, and Professor Demas for providing me wit h t he inspiring scient ific foundat ion t hat got me t here.

15 Questions?