Rene Pierpont, M. S.

      Mark S. Seidenberg, Ph.D.

E-mail: eipierpont@wisc.edu

Phone: (608) 772-1980

Office Location: 1202 W. Johnson St.  Madison, WI 53726

ABOUT NOONAN SYNDROME

Noonan syndrome (NS) is a genetic condition with variable expression that is characterized by multiple physical and cardiac anomalies. The estimated incidence rate is 1/1000 to 1/2500 births¹, and males and females are equally affected².  A summary of disease characteristics, diagnostic testing and management options can be found at genetests.org.  Links to other Noonan syndrome resources can be found here.  

What genes are associated with Noonan Syndrome?

Genetic heterogeneity is a well-established feature of Noonan syndrome³.  This means that the condition can be caused by multiple different genetic mechanisms.  NS is frequently inherited through parent-to-child transmission, but can also be  sporadically transmitted².

Approximately 50% of individuals with Noonan syndrome test positive for mutation in the PTPN11 gene⁴.  The major protein that this gene produces (SHP-2) is an important component of signal transduction pathways which control various developmental processes⁵. Recently, three more genes for Noonan syndrome have been identified. These genes include SOS1⁶, RAF1⁷, and KRAS⁸. Gene testing is currently commercially available for all four of these genes.

What are the effects of Noonan Syndrome on cognitive and language development?

Although Noonan Syndrome can affect development of aspects of cognition, the disorder is not associated with severe impairments of intellectual functioning⁹.  Prevalence of speech and language delays or learning disabilities have been noted in several studies of NS ^10-12.  However, only limited information is available about specific characteristics of language development (e.g., typical strengths and weaknesses, developmental trajectory).  The aim of the Language Development in Noonan Syndrome (LDNS) research project at the University of Wisconsin is to obtain more information about language ability in children and young adults with NS, and to examine how these skills relate to other aspects of cognitive and psychological functioning. We are also interested in identifying risk factors for communication and learning disabilities in NS.  We hope that our research will benefit families and clinicians who want to know more about Noonan syndrome.

References:

(1) Nora, J., Nora, A. H., Sinha, A. K., Spangler, R. D., & Lubs, H. A. (1974). The Ullrich-Noonan Syndrome (Turner phenotype). American Journal of Diseases of Children, 127(1), 48-55.

(2) Teeter, P. A. (1999). Noonan Syndrome. In S. Goldstein & C. Reynolds (Eds.), Handbook of Neurodevelopmental and Genetic Disorders in Children (pp. 337-149). New York: The Guilford Press.

(3)  van Der Burgt, I., & Brunner, H. (2000). Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form. American Journal of Medical Genetics, 94(1), 46-51.

(4) Tartaglia, M., Mehler, E. L., Goldberg, R., Zampino, G., Brunner, H. G., Kremer, H., et al. (2001). Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nature Genetics, 29(4), 465-468.

(5) Tartaglia, M., Kalidas, K., Shaw, A., Song, X., Musat, D. L., van der Burgt, I., et al. (2002). PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. American Journal of Human Genetics, 70(6), 1555-1563.

(6) Roberts, A., Araki, T., Swanson, K., Montgomery, K., Schiripo, T., Joshi, V., et. al. (2007). Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nature Genetics, 39(1), 70-74.

            (7) Schubbert, S., Zenker, M., Rowe, S., Boll, S., Klein, C., Bollag, G., et al. (2006). Germline KRAS mutations cause Noonan syndrome. Nature Genetics, 38(3), 331-336.

(8) Razzaque, M. A. et al. (2007) Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature Genetics, 39, 1013 – 1017.

(9) van der Burgt, I., Thoonen, G., Roosenboom, N., Assman-Hulsmans, C., Gabreels, F., Otten, B., et al. (1999). Patterns of cognitive functioning in school-aged children with Noonan syndrome associated with variability in phenotypic expression. Journal of Pediatrics, 135(6), 707-713. 

(10) Wilson, M., & Dyson, A. (1982). Noonan Syndrome: speech and language characteristics. Journal of Communication Disorders, 15, 347-352.

(11) Hopkins-Acos, P., & Bunker, K. (1979). A child with Noonan Syndrome. Journal of Speech and Hearing Disorders, 44(4), 494-503.

(12) Money, J., & Kalus, M. E. (1979). Noonan Syndrome: IQ and specific disabilities. American Journal of Diseases of Children, 133(8), 846-850.