Turner Syndrome with normal karyotype; Pseudo Turner syndrome; Male Turner syndrome; Ullrich syndrome .
Noonan syndrome was first described by Noonan and Ehmke in 1963. Jacqueline Noonan described 19 cases of this syndrome in 1968, which were similar to the disorder described by Turner, but with normal karyotype .
The incidence of the Noonan syndrome is between 0.5 - 1:1000 .
Noonan is inherited in an autosomal dominant manner, although many cases are sporadic . Inheritance is more common through the maternal line, probably due to the high incidence of male subfertility [1-3]. 40% of cases are caused by mutations of PTPN11 gene. Some cases of the Noonan syndrome can arise de novo, so many cases are in fact sporadic. The gene responsible for the Noonan syndrome is located in the long arm of the chromosome 12 .
According to Nisbet, the recurrence risk is 5%, when the parents have only possible or no signs of Noonan syndrome .
Although the phenotype is distinctive and the syndrome may manifest at birth, the mean age when the Noonan syndrome is diagnosed is 9 years, as the dysmorphic features can be subtle.
The prenatal ultrasound findings reported in Noonan syndrome include accumulation of nuchal fluid, femur lengths at or just below the lower end of the normal range, pleural effusions, and renal anomalies. The most common prenatal features are polyhydramnios (58%), cystic hygroma (42%), increased thickness of the nuchal translucency and fetal hydrops (33%). Cardiac anomalies are present in 60% of cases: including left ventricular hypertrophy (25%), pulmonary stenosis (19%), atrial septal defect (10%) or dysplastic pulmonary valve in 7% .
During the prenatal period the symptoms may not be fully blown and sometimes can be visible only in a restricted time frame or are unspecific, and will not lead to an unequivocal diagnosis.
The diagnosis of the Noonan syndrome is usually made postnatally, unless a parent has an obvious Noonan syndrome phenotype. Nisbet et al (1999) demonstrate the diversity of the prenatal presentation. They propose to think about the diagnosis of the Noonan syndrome when faced with a fetus with a normal karyotype, but with varying degrees of edema or hydrops, with short femurs.
Nevertheless, several authors argue that the prenatal diagnosis of the Noonan syndrome is difficult and inefficient.
Turner syndrome: excluded in boys and by karyotype; Leopard syndrome: association of multiples lentigines with pulmonary stenosis and deafness; Costello syndrome; Escobar syndrome; Trisomy 21.
Ductal agenesis with no intrahepatic portion are described associated with Noonan Syndrome and in these cases drainage was possible directly into the right atrium, inferior vena cava or inferior vena cava via the iliac vein .
Ductal agenesis with iliac connection is a classic sign of Noonan syndrome. Drainage can also be directly into the right atrium, inferior vena cava or iliac vein.
According to Shah at al (1999), delayed gastrointestinal motor development is responsible for feeding problems . Prognosis is essentially dependent on congenital cardiovascular abnormalities. Without major cardiac anomalies, normal life expectancy can be presupposed.
Standard prenatal care is not altered when continuation of the pregnancy is chosen . Nevertheless, termination of pregnancy is possible, if serious cardiac anomalies are present. When a parent has Noonan syndrome or when a couple has had a child with Noonan syndrome before, detailed prenatal sonography should be done in the first, second and third trimester focused to the cardiac anomalies. The identification of increased nuchal fluid or hydrops in combination with borderline femurs" length and cardiac anomalies (especially pulmonary stenosis or dysplastic aortic valves), should also evoke a possibility of Noonan syndrome in the differential diagnostic consideration. Parents should be referred to a genetic counseling.
1. Bradley E., Kean L., Twining P., James D. Persistent right umbilical vein in a fetus with Noonan’s syndrome: a case report. Ultrasound Obstet Gynecol 2001; 17: 76-8.
2. Schlüter G., Steckel M., Schffmann H., Harms K., Viereck V., Emons G., Burfeind P., Pauer H.U. Prenatal DNA diagnosis of Noonan syndrome in a fetus with massive hygroma coli, pleural effusion and ascites. Prenat Diagn 2005; 25: 574-6.
3. Nisbet D.L., Griffin D.R., Chitty L.S. Prenatal features of Noonan syndrome. Prenatal Diagn 1999; 19: 642-7.
4. Jeanty P., Silva S.R., Leite J. Noonan Syndrome. Thefetus.net 2006-01-18.
5. Burglen L. Le syndrome de noonan. Aspects anténatals, devenir postnatal, aspects génétiques et diagnostiques. Med Foet Echo Gynecol 2002; 50: 9-12.
6. Shah N., Rodriguez M., St-Louis D., Kindley K., Milla M.J. Feeding difficulties and foregut dysmotility in Noonan’s syndrome. Arch Dis Child 1999; 81: 28-31.