Genotypic and phenotypic characterization of Noonan syndrome: New data and review of the literature

Marjolijn Jongmans, Erik A. Sistermans*, Alwin Rikken, Willy M. Nillesen, Rienk Tamminga, Michael Patton, Esther M. Maier, Marco Tartaglia, Kees Noordam, Ineke Van Der Burgt

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, minor facial anomalies, and congenital heart defects. In approximately 50% of cases the condition is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the protein SHP-2. In this study, PTPN11 mutation analysis was performed in 170 NS patients. In 76 (45%) of them a mutation was identified. We report on the distribution of these mutations, as well as on genotype-phenotype relationships. The benefit of the NS scoring system developed by van der Burgt et al. [(1994); Am J Med Genet 53:187-191] is shown, among physicians who consequently based their diagnosis on the NS scoring system the percentage mutation positive subjects was 54%, whereas this percentage was only 39% among physicians who made less use of the scoring system. In two patients with some uncommon manifestations mutations were found in the C-SH2 domain, a region in which defects are not often identified in NS. A trend was observed in patients carrying the 922A → G change (Asn308Asp) receiving normal education. In one patient with NS and mild juvenile myelomonocytic leukemia (JMML) the mutation 218C → T (Thr73Ile) was found. This confirms previous findings indicating that individuals with NS with specific mutations in PTPN11 are at risk of developing JMML.

Original languageEnglish
Pages (from-to)165-170
Number of pages6
JournalAmerican Journal of Medical Genetics
Volume134 A
Issue number2
Publication statusPublished - 15 Apr 2005

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