Premium
The face of Noonan syndrome: Does phenotype predict genotype
Author(s) -
Allanson Judith E.,
Bohring Axel,
Dörr HelmuthGuenther,
Dufke Andreas,
GillessenKaesbach Gabrielle,
Horn Denise,
König Rainer,
Kratz Christian P.,
Kutsche Kerstin,
Pauli Silke,
Raskin Salmo,
Rauch Anita,
Turner Anne,
Wieczorek Dagmar,
Zenker Martin
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33518
Subject(s) - noonan syndrome , ptpn11 , kras , costello syndrome , genotype , genetics , phenotype , mutation , biology , gene
The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty‐two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11 , which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio‐facio‐cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. © 2010 Wiley‐Liss, Inc.