Attention deficit in patients with Noonan Syndrome (NS)

Aims: Noonan Syndrome (NS) is a common autosomal-dominant developmental disorder with typical facial anomalies, congenital heart defects and short stature. Patients with NS typically show variable cognitive deficits including mental retardation and attention deficit. NS is caused by different activating mutations of the RAS-MAPK signaling pathway resulting in altered cellular learning mechanisms (LTP, long-term potentiation). In previous studies we could demonstrate a reduced LTP-like plasticity in patients with NS induced by transcranial magnetic stimulation. The aim of the present study is the systematic evaluation of attention abilities in NS.

Methods: In this study data are presented from 10 individuals with NS (aged 15 to 25; mean age 18.8±3.8 years) and 10 healthy individuals (aged 15 to 24; mean age 20.9±3.4 years). Using standardized computer-based measures of attention (Test of Variables of Attention, TOVA; Test of Attentional Performance, TAP), we evaluated long-term as well as short-term maintenance of attention by recording response times and error ratios. Statistical evaluation was performed via analysis of variance (ANOVA) and unpaired t-tests with Bonferroni-Holm correction. Level of significance was set at p<0.05.

Results: Concerning the TOVA, response time of patients with NS was significantly longer (p=0.033), response time variability (p=0.006) and the amount of impulsivity errors (p=0.006) were significantly enlarged. The ADHD score significantly differed (p=0.002) between groups. Regarding the performed tests of the TAP (Alertness, Visual Scanning, GoNogo and Incompatibility), the NS group showed significantly longer response times in the GoNogo (p=0.001) and the Incompatibility paradigm (CC p=0.003; nCC p=0.002).

Conclusion: Patients with NS show significant attention deficits. These impairments can be considered as the clinical correlate of cellular plasticity deficits based on the present RAS-pathway disorder. In this context these attentional deficits could be responsible for the frequent learning disabilities described in patients with NS.

Noonan Syndrome (NS) - attention deficit - RAS-MAPK pathway - long-term potentiation (LTP) - learning deficit