Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care.
22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Under-diagnosis in adults is common and recognition of facial dysmorphic features can be affected by age and ethnicity. This study aims to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients with conotruncal anomalies and to delineate their facial dysmorphisms and extra-cardiac manifestations. We recruited consecutively 156 patients with conotruncal anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ hybridization. Assessment for dysmorphic features was performed by a cardiologist at initial screening and then by a clinical geneticist upon result disclosure. Clinical photographs were taken and childhood photographs collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal anomalies. While dysmorphic features were detected by our clinical geneticist in all patients, only two-thirds were considered dysmorphic by our cardiologist upon first assessment. Evolution of facial dysmorphic features was noted with age. Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal defects is common and facial dysmorphic features may not be reliably recognized in the setting of adult CHD clinic, referral for genetic evaluation and molecular testing for 22q11.2DS should be offered to patients with conotruncal defects.
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Anthony P Y
AP
Liu
Department of Paediatric Cardiology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Pak-Cheong
PC
Chow
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Pamela P W
PP
Lee
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Gary T K
GT
Mok
Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Wing-Fai
WF
Tang
Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Obstetrics & Gynaecology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Elizabeth T
ET
Lau
Clinical Genetic Service, Department of Health, Hong Kong SAR, China.
Stephen T S
ST
Lam
Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Obstetrics & Gynaecology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Kelvin Y
KY
Chan
Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Obstetrics & Gynaecology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Anita S Y
AS
Kan
Department of Paediatric Cardiology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
Adolphus K T
AK
Chau
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Yiu-Fai
YF
Cheung
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Yu-Lung
YL
Lau
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: bhychung@hku.hk.
Brian H Y
BH
Chung
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D006330:Heart Defects, Congenital / Q000208:ethnology / Q000235:genetics*; D006723:Hong Kong; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D055815:Young Adult
22q11.2 deletion syndrome (22q11.2DS); Adult; Chinese; Congenital heart disease; Conotruncal anomaly; Dysmorphism