Browsing by Author "Kruszka, P."
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Item Cornelia de Lange syndrome in diverse populations(American Journal of Medical Genetics, Part A, 2019-02) Dowsett, L.; Porras, A.R.; Kruszka, P.; Davis, B.; Hu, T.; Honey, E.; Badoe, E.; Thong, M.K.; Leon, E.; Girisha, K.M.; Shukla, A.Cornelia de Lange syndrome (CdLS) is a dominant multisystemic malformation syndrome due to mutations in five genes—NIPBL, SMC1A, HDAC8, SMC3, and RAD21. The characteristic facial dysmorphisms include microcephaly, arched eyebrows, synophrys, short nose with depressed bridge and anteverted nares, long philtrum, thin lips, micrognathia, and hypertrichosis. Most affected individuals have intellectual disability, growth deficiency, and upper limb anomalies. This study looked at individuals from diverse populations with both clinical and molecularly confirmed diagnoses of CdLS by facial analysis technology. Clinical data and images from 246 individuals with CdLS were obtained from 15 countries. This cohort included 49% female patients and ages ranged from infancy to 37 years. Individuals were grouped into ancestry categories of African descent, Asian, Latin American, Middle Eastern, and Caucasian. Across these populations, 14 features showed a statistically significant difference. The most common facial features found in all ancestry groups included synophrys, short nose with anteverted nares, and a long philtrum with thin vermillion of the upper lip. Using facial analysis technology we compared 246 individuals with CdLS to 246 gender/age matched controls and found that sensitivity was equal or greater than 95% for all groups. Specificity was equal or greater than 91%. In conclusion, we present consistent clinical findings from global populations with CdLS while demonstrating how facial analysis technology can be a tool to support accurate diagnoses in the clinical setting. This work, along with prior studies in this arena, will assist in earlier detection, recognition, and treatment of CdLS worldwide.Item Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa(Mary Ann Liebert Inc, 2018-05) Thomford, N.E.; Dzobo, K.; Yao, N.A.; Chimusa, E.; Evans, J.; Okai, E.; Kruszka, P.; Muenke, M.; Awandare, G.; Wonkam, A.; Dandara, C.Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, ventricular septal defect (VSD), Tetralogy of Fallot (TOF), and patent ductus arteriosus phenotypes and 22q.11 deletion, which is associated with TOF. There were no data on epigenomic association of CHD in Africa, however, other studies have shown an altered expression of miR-421 and miR-1233-3p to be associated with TOF and hypermethylation of CpG islands in the promoter of SCO2 gene also been associated with TOF and VSD in children with non-syndromic CHD. These findings signal the urgent need to develop and implement genetic and genomic research on CHD to identify the hereditary and genome-environment interactions contributing to CHD. These projected studies would also offer comparisons on CHD pathophysiology between African and other populations worldwide. Genomic research on CHD in Africa should be developed in parallel with next generation technology policy research and responsible innovation frameworks that examine the social and political factors that shape the emergence and societal embedding of new technologies. © 2018, Mary Ann Liebert, Inc.Item Turner syndrome in diverse populations(American Journal of Medical Genetics, 2019-12-19) Badoe, E.; Kruszka, P.; Addissie, Y.A.; Tekendo-Ngongang, C.; Jones, K.L.; Savage, S.K.; Gupta, N.; Sirisena, N.D.; Dissanayake, V.H.W.; Paththinige, C.S.; Aravena, P.; Nampoothiri, S.; Yesodharan, D.; Girisha, K.M.; Patil, S.J.; Jamuar, S.S.; Goh, J.C-Y.; Utari, A.; Sihombing, N.; Mishra, R.; Chitrakar, N.S.; Iriele, B.C.; Lulseged, E.; Megarbane, A.; Uwineza, A.; Oyenusi, E.E.; Olopade, O.B.; Fasanmade, O.A; Duenas-Roque, M.M.; Thong, M-V.; Tung, J.Y.L.; De Herreros, M.B.; Watts, J.; Fieggen, K.; Huckstadt, V.; Moresco, A.; Obregon, M.G.; Hussen, D.F.; Ashaat, N.A.; Ashaat, E.A.; Chung, B.H.Y.; Faradz, S.M.H.; Ruby, M.O.E.; Shotelersuk, V.; Wonkam, A.; Ekure, E.N.; Phadke, S.R.; Richieri-Costa, A.; Muenke, M.Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndromeItem Williams–Beuren syndrome in diverse populations(American Journal of Medical Genetics, Part A, 2018-05) Kruszka, P.; Porras, A.R.; de Souza, D.H.; Moresco, A.; Huckstadt, V.; Gill, A.D.; Boyle, A.P.; Hu, T.; Addissie, Y.A.; Mok, G.T.K.; Tekendo-Ngongang, C.et.al.Williams-Beuren syndrome (WBS) is a common microdeletion syndrome characterized by a 1.5Mb deletion in 7q11.23. The phenotype of WBS has been well described in populations of European descent with not as much attention given to other ethnicities. In this study, individuals with WBS from diverse populations were assessed clinically and by facial analysis technology. Clinical data and images from 137 individuals with WBS were found in 19 countries with an average age of 11 years and female gender of 45%. The most common clinical phenotype elements were periorbital fullness and intellectual disability which were present in greater than 90% of our cohort. Additionally, 75% or greater of all individuals with WBS had malar flattening, long philtrum, wide mouth, and small jaw. Using facial analysis technology, we compared 286 Asian, African, Caucasian, and Latin American individuals with WBS with 286 gender and age matched controls and found that the accuracy to discriminate between WBS and controls was 0.90 when the entire cohort was evaluated concurrently. The test accuracy of the facial recognition technology increased significantly when the cohort was analyzed by specific ethnic population (P-value < 0.001 for all comparisons), with accuracies for Caucasian, African, Asian, and Latin American groups of 0.92, 0.96, 0.92, and 0.93, respectively. In summary, we present consistent clinical findings from global populations with WBS and demonstrate how facial analysis technology can support clinicians in making accurate WBS diagnoses.