Characterizing the Phenotype of Williams- Beuren Syndrome in Diverse Populations

Transcription

1 1 Characterizing the Phenotype of Williams- Beuren Syndrome 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. 2 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 3 Objective To characterize the phenotype of Williams-Beuren Syndrome in underrepresented non-caucasian populations in order to enhance the ability to clinically diagnose Williams-Beuren Syndrome across diverse populations.

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

5 5 Procedure and Methods 41 patients have been clinically diagnosed with Williams-Beuren Syndrome 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 objective facial characterization instrument.

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

7 Face2Gene Face2Gene uses Bayesian networks to assess the probability 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. 7

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

9 Results 9

10 10 Results Sensitivity= Number of True Positives Number of True Positives + False Negatives X 100

11 11 Discussion Williams-Beuren Syndrome lacks definition in underprivileged non-caucasian populations due to the small amount of reported cases. The distinctive facies characterizing Williams- Beuren Syndrome 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 12 Conclusion Williams-Beuren Syndrome in individuals from diverse populations is under-represented 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 Syndrome in individuals.

13 13 Future Directions Characterizing Williams-Beuren Syndrome in diverse populations from Asia, Sub-Saharan Africa, Latin American, and the Middle East. Adding a control sample consisting of individuals with syndromic diagnoses not including Williams-Beuren Syndrome to further statistical analysis. Quantifying observer variation through blind testing of unrelated clinicians. Testing the accuracy and precision of FDNA analysis using Face2Gene technology on individuals with a wide variety of syndromes.

14 14 Acknowledgements Many thanks go to the generous donors to the College Science Scholars program who make these summer research awards possible: Charles Henry Leach, II, Foundation, Mr. Steve Van Besien; Entigence Corporation; Lois A. Fitton & W. Christopher Draper, Jr.; Sharon B. Parente & John W. Risner; The Jefferson Trust; Robert Atkinson; Lowe Family; Dean s discretionary gifts. I sincerely thank Dr. Muenke and Dr. Kruszka for providing me with the life-changing opportunity of researching at the National Institutes of Health, and Professor Schmidt, Professor Epstein, and Professor Demas for providing me with the inspiring scientific foundation that got me there.

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