The face of Noonan syndrome: Does phenotype predict genotype.
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.
Allanson
Judith E
JE
Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Bohring
Axel
A
Dörr
Helmuth-Guenther
HG
Dufke
Andreas
A
Gillessen-Kaesbach
Gabrielle
G
Horn
Denise
D
König
Rainer
R
Kratz
Christian P
CP
Kutsche
Kerstin
K
Pauli
Silke
S
Raskin
Salmo
S
Rauch
Anita
A
Turner
Anne
A
Wieczorek
Dagmar
D
Zenker
Martin
M
D000015:Abnormalities, Multiple; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020837:SOS1 Protein / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D020837:SOS1 Protein; D019908:Proto-Oncogene Proteins c-raf; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins