Neuropediatrics 2010; 41 - P1368
DOI: 10.1055/s-0030-1265613

Impaired motor cortex plasticity in patients with Noonan syndrome

F Mainberger 1, M Zenker 2, N Jung 1, I Delvendahl 1, A Brandt 1, L Freudenberg 1, A Pechmann 1, F Heinen 3, V Mall 1
  • 1Division of Neuropaediatrics and Muscular Disorders, Department of Paediatrics and Adolescent Medicine, University Medical Centre Freiburg, Germany
  • 2Institute of Human Genetics, University Hospital Erlangen and Institute of Human Genetics, University Hospital Magdeburg, Germany
  • 3Department of Paediatric Neurology and Developmental Medicine, Dr. von Haunersches Kinderspital, Ludwig-Maximilians-University Munich, Germany

Objective: Noonan syndrome (NS; OMIM 163950) is a developmental disorder characterized by short stature, congenital heart defects, facial anomalies and variable learning deficits. NS is caused by activating mutations in various components of the RAS-MAPK pathway. Recent in vitro studies demonstrated impairment of synaptic plasticity caused by RAS-MAPK pathway hyperactivity. We therefore intended to find a clue to synaptic plasticity in patients with NS.

Methods: We investigated 8 patients with Noonan syndrome and an age and gender matched control group using paired associative stimulation (PAS). Changes in MEP amplitudes were assessed immediately after as well as 30 and 60 minutes after PAS.

Results: We demonstrated that MEP amplitudes of healthy controls significantly increased from 1.03±0.18 to 1.81±0.61 mV (p=0.006), which was not seen in patients with Noonan-Syndrome (0.88±0.1 to 1.2±0.49 mV, p=0.103) and that there was a significant difference between both groups 60min after PAS (p=0.044).

Conclusions: Our study provides first evidence that synaptic plasticity is impaired in patients with NS which is probably a consequence of constitutive activity of the RAS-MAPK pathway.

Significance: This is the first study that indicated impaired synaptic plasticity in patients with a RAS-pathway disorder.