22q11.2 deletion syndrome in adult Chinese Patients with Conotruncal Anomalies: dysmorphisms, clinical features and underdiagnosis

Abstract

22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Underdiagnosis in adults is common and recognition of facial dysmorphic features can be affected by patient 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 dysmorphic features 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 hybridisation. 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 with consent and childhood photographs were collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognised 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%), hypocalcaemia (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 recognised in the setting of adult CHD clinic. In order to avoid missing the diagnosis, molecular testing of 22q11.2DS should be offered to patients with conotruncal defects regardless of the facial features.