22q11.2 deletion syndrome in diverse populations.
22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P < 0.05). However, when Africans were removed from analysis, six additional clinical features were found to be independent of ethnicity (P ≥ 0.05). Using facial analysis technology, we compared 156 Caucasians, Africans, Asians, and Latin American individuals with 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world.
Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Paul
http://orcid.org/0000-0003-4949-0875
P
Kruszka
Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Yonit A
YA
Addissie
Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Daniel E
DE
McGinn
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, D.C.
Antonio R
AR
Porras
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, D.C.
Elijah
E
Biggs
Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Matthew
M
Share
Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
T Blaine
TB
Crowley
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
Brian H Y
BH
Chung
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
Gary T K
GT
Mok
Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
Christopher C Y
CC
Mak
Faculty of Medicine, Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.
Premala
P
Muthukumarasamy
Faculty of Medicine, Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.
Meow-Keong
MK
Thong
Faculty of Medicine, Human Genetics Unit, University of Colombo, Sri Lanka.
Nirmala D
ND
Sirisena
Faculty of Medicine, Human Genetics Unit, University of Colombo, Sri Lanka.
Vajira H W
VH
Dissanayake
Faculty of Medicine, Human Genetics Unit, University of Colombo, Sri Lanka.
C Sampath
CS
Paththinige
Faculty of Medicine, Human Genetics Unit, University of Colombo, Sri Lanka.
L B Lahiru
LB
Prabodha
Faculty of Medicine, Human Genetics Unit, University of Colombo, Sri Lanka.
Rupesh
R
Mishra
Center of Excellence for Medical Genetics, Faculty of Medicine, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
Vorasuk
V
Shotelersuk
Department of Paediatrics College of Medicine, University of Lagos, Lagos University Teaching, Lagos, Nigeria.
Ekanem Nsikak
EN
Ekure
Department of Paediatrics College of Medicine, University of Lagos, Lagos University Teaching, Lagos, Nigeria.
Ogochukwu Jidechukwu
OJ
Sokunbi
Department of Paediatrics College of Medicine, University of Lagos, Lagos University Teaching, Lagos, Nigeria.
Nnenna
N
Kalu
Division of Genetics and Metabolism, Children's National Health System, Washington, D.C.
Carlos R
CR
Ferreira
Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Jordann-Mishael
JM
Duncan
Mazumdar Shaw Medical Center, Narayana Health City, Bangalore, India.
Siddaramappa Jagdish
SJ
Patil
Division of Medical Genetics, Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
Kelly L
KL
Jones
Division of Medical Genetics, Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
Julie D
JD
Kaplan
Division of Medical Genetics, Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
Omar A
OA
Abdul-Rahman
Center of Human Genetics/School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
Annette
A
Uwineza
Center of Human Genetics/School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
Leon
L
Mutesa
Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
Angélica
A
Moresco
Servicio de Genética, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
María Gabriela
MG
Obregon
Hospital for the Rehabilitation of Craniofacial Anomalies, São Paulo University, Bauru, Brazil.
Antonio
A
Richieri-Costa
Department of Medical Genetics, University of Campinas, São Paulo, Brazil.
Vera L
VL
Gil-da-Silva-Lopes
Center for Research on Genomics and Global Health, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Adebowale A
AA
Adeyemo
Division of Genetics and Metabolism, Children's National Health System, Washington, D.C.
Marshall
M
Summar
Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Elaine H
EH
Zackai
Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Donna M
DM
McDonald-McGinn
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, D.C.
Marius George
MG
Linguraru
Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
Maximilian
M
Muenke
D000293:Adolescent; D000328:Adult; D044466:Asian People; D056667:Biometric Identification / Q000379:methods*; D044383:Black People; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22 / Q000737:chemistry; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D019066:Facies; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D006630:Hispanic or Latino; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007859:Learning Disabilities / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D044465:White People
22q11.2 Deletion syndrome; DiGeorge syndrome; Velocardiofacial Syndrome; diverse populations; facial analysis technology