Noonan syndrome

What is Noonan Syndrome (NS)?

Much of the Rasopathies research Dr. Pierpont has completed to date examines the neuropsychological features of Noonan syndrome (NS). NS is a genetic syndrome characterized by short stature, cardiac disease, skeletal and skin anomalies, and variable learning disabilities. Mutations in the PTPN11, SOS1, KRAS, NRAS, RAF1, SHOC2, CBL, MEK1, and BRAF genes account for 60-80% of cases of clinically diagnosed NS. More genes are continually being discovered! Intellectual functioning in Noonan syndrome is generally within the average range, although there is a heightened risk for intellectual disability (ID). In one study, we found that children with mutations in the SOS1 gene typically did not demonstrate impairments in intellectual functioning. Individuals with mutations in PTPN11 and unknown mutations were a significantly higher risk for intellectual deficits, although the range of cognitive abilities in these individuals varied from moderately impaired to above average. The figure below shows the distributions of scores on a test of intellectual functioning among patients with different mutations.

Noonan Syndrome Research

Pierpont, et al. (2009) Genes, Brain & Behavior

In this study, we also found that children with NS who had better verbal intellectual functioning also tended to have better fine motor dexterity, better hearing ability on audiological testing, and parents with higher levels of education. Interestingly, while congenital heart disease was present among many patients in the sample, the severity of children's cardiac disease did not predict cognitive ability.

We have also conducted studies examining language abilities in children with Noonan syndrome. We found that children with NS are at higher risk for language impairments than the general population. Below is a pie chart depicting performance of a group of 66 children with Noonan syndrome on a standardized language test that is frequently used in clinical settings:

Mean standard score = 88.9, standard deviation = 20.3, range = 44 to 120

We found that language ability in NS was significantly correlated with nonverbal cognitive ability, articulation, hearing loss, manual motor skill and phonological memory. Therefore, children with language problems were more likely to have difficulties in other areas of development.

In study that was recently published in the American Journal of Medical Genetics, we investigated learning and memory abilities in children with Noonan syndrome. This study found that children with NS tend to have better recognition memory (i.e., the ability to recognize information they have previously seen when provided with choices) as compared to recall memory (i.e., the ability to retrieve information stored in memory in an organized way). This finding is significant both because it provides information regarding possible underlying brain regions that may be affected by NS, and also because it suggests that children with NS may better be able to demonstrate learning when tested in a recognition rather than a recall format. Intriguingly, another research group reported a similar finding of impaired recall memory relative to recognition memory in Costello syndrome. This suggests that brain development may be impacted in similar ways across the Rasopathies! Indeed, avenues for educational interventions relevant to NS may also be relevant to other genetically similar syndromes.

Our study of learning and memory provided other insights into learning differences in NS as well. First, we found that verbal memory was, on average, stronger than nonverbal (visual) memory and working memory. Working memory is the ability to hold information in mind for short periods while using it. Children with NS generally performed more poorly compared to the normative population on working memory tests. We also found that children with NS remembered information better when it was provided in a contextual format (e.g., stories) than when it was presented in a rote format (e.g., a list of unrelated words). Performance of children with NS on the standardized battery of memory and learning tasks is depicted below.

Performance of 29 children and adolescents with NS on subtests of the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2).

If you are interested in learning more about neuropsychological functioning in individuals with Noonan syndrome, you may be interested in this review article! You can download it free from the publisher website.