Updated 2006-01-18 by Juliana Leite, MD
Original text 1999-05-27 Philippe Jeanty, MD, PhD & Sandra R Silva, MD
Synonyms: Turner syndrome with normal XX, pseudo-Turner syndrome, male Turner syndrome, Ullrich syndrome.
Definition: In 1968, Jacqueline A. Noonan described 19 cases of a syndrome very similar to the disorder described by Turner. Among her patients, 17 had pulmonary stenosis and 2 had patent ductus arteriosus (12 males and 7 females). Other anomalies included lymphedema, pterygium colli, deformity of the sternum with precocious closure of sutures resulting in a pectus carinatum superiorly and a pectus excavatum inferiorly, coarctation of the aorta, cryptorchidism, and thrombocytopenia. Aside from this syndrome occurring in both genders, there is a large phenotypic overlap with Turner syndrome.
Incidence: Its prevalence is 4 to 10:10,000 births
Etiology: Autosomal-dominant with sporadic new mutations.
Diagnosis: The initial anomaly most likely to be observed is a posterior nuchal cystic hygroma, which may regress later in the gestation into a nuchal fold redundancy and/or pterygium colli. Other fetuses have been suspected because of special facial features (low-set ears, depressed nasal bridge, and large head), congenital heart disease, pleural effusions, renal abnormalities, polyhydramnios, short stature, hydrops and familiar history. Some fetuses have been identified by triple marker screening, too. Congenital heart disease may appear in up to 60% of Noonan syndrome patients. In fact, cardiac abnormality associated with cervical lymphatic abnormalities may provide the only clues to diagnoses of Noonan syndrome. In literature, three cases of persistent right umbilical vein with no intrahepatic portion are described associated with Noonan Syndrome. In these cases drainage was possible directly into the right atrium, inferior vena cava (IVC) or IVC via the iliac vein. Amelioration of early nuchal region findings in a fetus with a normal karyotype and late onset of the more "typical" ultrasonographic changes may limit early prenatal detection. Noonan syndrome is yet diagnosed at birth or during childhood.
Genetic anomalies: X-linked dominant inheritance of either a single mutant gene or a submicroscopic deletion was originally suspected, but now it is recognized that one of the genes for Noonan syndrome is located on chromosome 12 in the 12q24.2–q24.31 region.
Differential diagnosis: Turner syndrome (excluded in boys or otherwise by karyotype) is also unlikely to be familial, whereas Noonan syndrome has a strong familial predilection; trisomy 21; Escobar syndrome.
Prognosis: Fairly normal life expectancy for those without major complications of heart disease. After a thoracoamniotic shunting, pleural effusion with hydrops has a 57% survival rate; premature delivery is the leading source of morbidity.
Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation of the pregnancy is chosen.
References
1. Joo JG, Beke A, Toth-Pal E, Csaba A, Papp C. Successful pregnancy in a Noonan syndrome patient after 3 unsuccessful pregnancies from severe fetal hydrops: a case report. J Reprod Med. 2005 May; 50(5):373-6.
2. Picone O, Benachi A, Mandelbrot L, Ruano R, Dumez Y, Dommergues M. Thoracoamniotic shunting for fetal pleural effusions with hydrops. Am J Obstet Gynecol. 2004 Dec; 191(6):2047-50.
3. 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 Jan; 17(1):76-8.
4. Achiron R, Heggesh J, Grisaru D et al. Noonan syndrome: a cryptic condition in early gestation. Am J Med Genet. 2000 May 29; 92(3):159-65.
5. Nisbet DL, Griffin DR, Chitty LS.Prenatal features of Noonan syndrome. Prenat Diagn. 1999 Jul; 19(7):642-7.