Neuropsychiatric aspects of 22q11.2 deletion syndrome: considerations in the prenatal setting

Abstract

Most major neuropsychiatric outcomes of concern to families are not detectable by prenatal ultrasound. The introduction of genome-wide chromosomal microarray analysis to prenatal clinical diagnostic testing has increased the detection of pathogenic 22q11.2 deletions, which cause the most common genomic disorder. The recent addition of this and other microdeletions to non-invasive prenatal screening methods using cell-free fetal DNA has further propelled interest in outcomes. Conditions associated with 22q11.2 deletions include intellect ranging from intellectual disability to average, schizophrenia and other treatable psychiatric conditions, epilepsy, and early-onset Parkinson's disease. However, there is currently no way to predict how severe the lifetime expression will be. Available evidence suggests no major role in these neuropsychiatric outcomes for the congenital cardiac or most other structural anomalies that may be detectable on ultrasound. This article provides an outline of the lifetime neuropsychiatric phenotype of 22q11.2 deletion syndrome that will be useful to clinicians involved in prenatal diagnosis and related genetic counselling. The focus is on information that will be most relevant to two common situations: detection of a 22q11.2 deletion in a fetus or newborn, and new diagnosis of 22q11.2 deletion syndrome in a parent without a previous molecular diagnosis. © 2016 John Wiley & Sons, Ltd.

Figure 1

shows approximate values for risk estimates available for the neuropsychiatric features of 22q11.2DS (orange bars) known to differ significantly from general population estimates (blue bars). Prevalence estimates for 22q11.2DS are from Fung et al. 2015 and from standard sources for population estimates.^, Where ranges were provided, the lower value was used for 22q11.2DS. Neuropsychiatric disorders are ordered by expected age at detection. Intellectual disability ranges from mild (most common) to severe. Other associated neuropsychiatric conditions for which consistent prevalence estimates for 22q11.2DS are not yet available and/or may overlap with population prevalence are not shown; these would include developmental delay, hypotonia, autism spectrum disorder, and attention deficit hyperactivity disorder.