TY - CHAP
T1 - Genotype-phenotype correlations in Noonan syndrome
AU - Sarkozy, Anna
AU - Digilio, M. C.
AU - Marino, B.
AU - Dallapiccola, B.
PY - 2009
Y1 - 2009
N2 - Noonan syndrome (NS) is an autosomal dominant disorder mainly characterized by short stature, distinct facial anomalies and congenital heart defects. The cumulative record of genotype-phenotype correlations clearly indicates that PTPN11 gene mutations, responsible for almost half of the cases, either sporadic or familial, are responsible for a wide clinical spectrum, characterized by a high prevalence of pulmonary valve stenosis, typical facial features, cryptorchidism and bleeding diathesis. Mutations in the SOS1 gene are associated with clinical features partly overlapping those found in PTPN11 mutation-positive individuals, but distinguished by a low frequency of short stature and mental retardation, and a high prevalence of macrocephaly, ptosis, and skin features similar to those of cardio-facio-cutaneous syndrome (CFCS). RAF1 gene mutations are strongly associated with hypertrophic cardiomyopathy, mental retardation, short stature, and skin features of LEOPARD syndrome. Patients with KRAS mutations are sporadic, affected by variable mental retardation and may manifest features overlapping those of Costello and CFCS, while MEK1 mutations have been found so far only in two unrelated NS individuals.
AB - Noonan syndrome (NS) is an autosomal dominant disorder mainly characterized by short stature, distinct facial anomalies and congenital heart defects. The cumulative record of genotype-phenotype correlations clearly indicates that PTPN11 gene mutations, responsible for almost half of the cases, either sporadic or familial, are responsible for a wide clinical spectrum, characterized by a high prevalence of pulmonary valve stenosis, typical facial features, cryptorchidism and bleeding diathesis. Mutations in the SOS1 gene are associated with clinical features partly overlapping those found in PTPN11 mutation-positive individuals, but distinguished by a low frequency of short stature and mental retardation, and a high prevalence of macrocephaly, ptosis, and skin features similar to those of cardio-facio-cutaneous syndrome (CFCS). RAF1 gene mutations are strongly associated with hypertrophic cardiomyopathy, mental retardation, short stature, and skin features of LEOPARD syndrome. Patients with KRAS mutations are sporadic, affected by variable mental retardation and may manifest features overlapping those of Costello and CFCS, while MEK1 mutations have been found so far only in two unrelated NS individuals.
UR - http://www.scopus.com/inward/record.url?scp=79959725262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959725262&partnerID=8YFLogxK
U2 - 10.1159/000164838
DO - 10.1159/000164838
M3 - Chapter
AN - SCOPUS:79959725262
SN - 9783805586535
VL - 17
T3 - Monographs in Human Genetics
SP - 40
EP - 54
BT - Monographs in Human Genetics
ER -