Although risk for psychosis in velocardiofacial (22q11.2 deletion) syndrome (VCFS) is well established, the cognitive and familial factors that moderate that risk are poorly understood.

A total of 75 youth with VCFS were assessed at three time points, at 3-year intervals. Time 1 (T1) psychiatric risk was assessed with the Behavior Assessment System for Children (BASC). Data reduction of BASC scores yielded avoidance–anxiety and dysregulation factors. Time 2 (T2) neuropsychological and family function and time 3 (T3) prodromal/overt psychosis were assessed. Poisson regression models tested associations between T3 positive prodromal symptoms/overt psychosis and T1 psychiatric risk, T2 cognitive and familial factors, and their interactions.

T1 avoidance–anxiety ratings predicted T3 prodromal/overt psychosis. T2 verbal learning scores moderated this association, such that individuals with low avoidance–anxiety scores and stronger verbal learning skills were the least likely to demonstrate prodromal/overt psychosis at T3. Low scores on a T2 visual vigilance task also predicted T3 prodromal/overt psychosis, independently of the effect of T1 avoidance–anxiety scores. T1 dysregulation scores did not predict T3 prodromal/overt psychosis in a linear manner. Instead, the association between dysregulation and prodromal/overt psychosis was amplified by T2 levels of family organization, such that individuals with low dysregulation scores and low family organization scores were the most likely to exhibit T3 prodromal/overt psychosis.

Significant moderators of psychiatric risk in VCFS include verbal learning skills as well as levels of family organization, carrying implications for early identification and preventative treatment of youth with VCFS at highest risk for psychosis.

In both Prader-Willi syndrome (PWS) and 22q11 deletion syndrome [velo-cardio-facial syndrome (VCFS)], an increased risk for psychotic disorders is reported, which are as a rule not included in the behavioural phenotype of these two syndromes. For the description of a behavioural phenotype, the complete spectrum of physical, developmental, neuropsychological and psychiatric aspects is generally not taken into account. Moreover, psychiatric signs and symptoms often do not meet the criteria for a categorical diagnosis.

In this study, a further specification of psychotic symptoms in PWS and VCFS is shown as well as a proposal for a new model to ascertain predictors, including behavioural, for a genetic syndrome.

Over the past years, 27 patients with PWS and 19 with VCFS were referred for neuropsychiatric evaluation because of psychotic symptoms. In all the patients, a standardised psychiatric examination was performed; seven of the patients with VCFS were evaluated by means of an extensive neuropsychological battery.

In both patient groups, a rather specific psychopathological profile seemed to be present, which in the case of patients with PWS showed some resemblance with bipolar affective disorder. In patients with VCFS, no formal psychiatric diagnosis could be established. Because the psychopathological profiles were rather aspecific, they are not sufficient to predict membership of a certain syndrome.

A quantitative probabilistic approach toward the description of a (behavioural) phenotype is suggested. For such a procedure, large data sets and international collaboration are required.

22q11.2 microdeletion is the most common microdeletion in the global population. Congenital cardiac disease is the most frequently observed feature of this syndrome. The prognosis of patients with 22q11.2 copy number aberrations varies from those without 22q11.2 deletion or duplication.

We enrolled 241 patients from Nanjing Drum Tower Hospital and Nanjing Sick Children’s Hospital, 227 being scheduled for cardiac surgery, and 14 cases being fetuses aged from 24 to 36 gestational weeks. We performed karyotypic analysis and multiplex ligation-dependent probe amplification in all cases.

Karyotypic analysis demonstrated 3 cases with trisomy 21, and 1 case with mosaic trisomy 8 [47,XY,+8/46,XY(1:2)]. Multiplex ligation-dependent probe amplification analysis revealed 10 cases (4.15%) with changes in the number of copies within the region of 22q11.2, of which 7 cases were hemizygous interstitial microdeletion from CLTCL1 to LZTR1, 1 case with deletion of the region from CLTCL1 to PCQAP, and 2 cases with 22q11.2 duplication, one of which spanned from ZNF74 to LZTR1, and simultaneously showed trisomy 21 by karyotyping analysis, and the other spanned from HIC2 to TOP3B. The phenotypes of the cardiac lesions included 3 cases of ventricular septal defect, 3 of tetralogy of Fallot, 2 of combined ventricular and atrial septal defects, and 2 with pulmonary arterial stenosis.

Patients with congenitally malformed hearts who are scheduled for cardiac surgery, as well as fetuses with congenital cardiac disease, should routinely undergo karyotypic analysis and examination for 22q11.2 aberrations. Multiplex ligation-dependent probe amplification has been proven to be a cost-effective diagnostic technique for 22q11 deletion syndrome.