A recognisable behavioural phenotype associated with terminal deletions of the short arm of chromosome 8

Abstract

We report the clinical findings in 5 patients with a terminal deletion of the short arm of chromosome 8. Mild developmental delay was constantly present, in association with microcephaly in 4 of 5 patients. Facial anomalies were mild or absent. A congenital heart defect was present in 3 patients: an atrioventricular septal defect (AVSD) in 2 and an atrial septal defect type II (ASDII) with pulmonary stenosis in one. A highly similar pattern of behavioural difficulties was present in the 3 older children (8-11 years), with outbursts of aggressiveness and destructive behaviour. Follow-up in one patient showed that at the age of 16 years, these behavioural problems had largely disappeared. This observation suggests that in addition to mental retardation, microcephaly, congenital heart defect (typically AVSD), a terminal deletion of chromosome 8p may be associated with a characteristic behavioural phenotype during childhood.

Subtle familial unbalanced translocation t(8;11)(p23.2;p15.5) in two fetuses with Beckwith-Wiedemann features

“…To our knowledge only one case of 8p23.1 deletion has been detected prenatally due to the presence of a diaphragmatic hernia observed at second trimester ultrasound examination (Faivre et al, 1998). Terminal 8p deletion is usually associated with few or no major congenital anomalies (Wu et al, 1996;Claeys et al, 1997).…”

Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH)

“…8p deletions encompassing the 8p23.1 microdeletion region have previously been observed in a number of patients with CDH (Pecile et al, 1990 , 1996;Faivre et al, 1998;Borys and Taxy, 2004;Shimokawa et al, 2005;Slavotinek et al, 2005;Lopez et al, 2006;Baynam et al, 2008;Wat et al, 2009). In addition, deletions of this region are also associated with congenital heart defects (Claeys et al, 1997;Devriendt et al, 1998Devriendt et al, , 1999. GATA4 is considered to be the gene responsible for the heart abnormalities observed in patients with 8p deletions following the identification of GATA4 mutations in patients with congenital heart defects (Garg et al, 2003;Okubo et al, 2004;Reamon-Buettner and Borlak, 2005;Rajagopal et al, 2007;Reamon-Buettner et al, 2007;Tomita-Mitchell et al, 2007).…”

Microdeletions and molecular genetics

“…Other major manifestations include microcephaly, intrauterine growth retar-dation, mental retardation and a characteristic behavioural pattern. The behaviour is described as sudden and extreme outbursts of aggressiveness accompanied by destructive behaviour, low frustration tolerance, oppositional behaviour, hyper-activity and poor concentration [223].…”