Three infants with a prenatal diagnosis of Noonan's syndrome suffered fetal hydrops and immediate neonatal death. The infants all had the external appearance of jugular lymphatic obstruction sequence with wide-spaced nipples, redundant posterior nuchal skin, and edema of the dorsa of the feet and hands. All 3 demonstrated thick, redundant leaflets of all 4 cardiac valves, and 2 had a membranous ventricular septal defect. One female infant had a mutation of the PTPN11 gene. Two males had no common mutation of PTPN11. The males demonstrated other abnormalities in common, including small penis, testicular malformation, rosette-like appearance of the pituicytes, and an eosinophil infiltration of the pancreatic islets with islet cell hypertrophy. Detailed anatomy of cases of lymphatic obstruction sequence fetuses can be correlated with an increasing number of genetic mutations associated with Noonan's syndrome and related syndromes in mice and humans.
RushtonDFaedMRichardsSBainA. The fetal manifestations of the 45 XO karyotype. J Obstet Gynaec Br Cwlth1969;76:266–272.
2.
SinghRCarrD. The anatomy and histology of XO human embryos and fetuses. Anat Rec1966;155:369–384.
3.
SinghR. Hygroma of the neck in XO abortuses. Am J Clin Pathol1970;53:104–107.
4.
PolandBDillFParadiceB. A Turner-like phenotype in the aborted fetus. Teratology1980;21:361–365.
5.
ByrneJBlancWWharburtonDWiggerJ. The significance of cystic hygroma in fetuses. Hum Pathol1984;15:61–67.
6.
PearceJGriffinDCampbellS. Cystic hygromata in trisomy 18 and 21. Prenat Diagn1984;4:371–375.
7.
RedfordDMcNayMFerguson-SmithMJamiesonM. Aneuploidy and cystic hygroma detectable by ultrasound. Prenat Diagn1984;4:377–382.
8.
KalousekDSellerM. Differential diagnosis of posterior cervical hygroma in previable fetuses. Am J Med Genet1987;3(Suppl):83–92.
9.
AbramowiczJWarsofSDoyleDSmithDLevyD. Congenital cystic hygroma of the neck diagnosed prenatally: outcome with normal and abnormal karyotype. Prenat Diag1989;9:321–327.
10.
CowchockFWapnerRKurtzAChatzkelSBarnhartJJLesnickD. Brief clinical report: not all cystic hygromas occur in the Ullrich-Turner syndrome. Am J Med Genet1982;12:327–331.
11.
JonesKL. Smith's Recognizable Patterns of Human Malformation. Philadelphia: W.B. Saunders Company, 1988.
12.
van der PutteSCJ. Lymphatic malformation in human fetuses. Virchows Arch Pathol Anat1977;376:233.
13.
ShepardTWenerMMyhreSHickokD. Lowered plasma albumin concentration in fetal Turner syndrome. J Pediatr1986;108:114–116.
14.
MostelloDJBofingerMKSiddiqiTA. Spontaneous resolution of fetal cystic hygroma and hydrops in Turner syndrome. Obstet Gynecol1989;73:862–865.
15.
IzquierdoLKushnirOSanchezD. Prenatal diagnosis of Noonan's syndrome in a female infant with spontaneous resolution of cystic hygroma and hydrops. West J Med1990;152:418–421.
16.
BenacerrafBRGreeneMFHolmesLB. The prenatal sonographic features of Noonan's syndrome. J Ultrasound Med1989;8:59–63.
17.
Oudesluys-MurphyAM. Nonimmune hydrops fetalis in Noonan's syndrome. Am J Dis Child1987;141:478–479.
18.
BawleEVBlackV. Nonimmune hydrops fetalis in Noonan's syndrome. Am J Dis Child1986;140:758–760.
19.
RodriguezMMBruceJHJimenezXF. Nonimmune hydrops fetalis in the liveborn: series of 32 autopsies. Pediatr Dev Pathol2005;8:369–378.
20.
NisbetDLGriffinDRChittyLS. Prenatal features of Noonan syndrome. Prenat Diagn1999;19:642–647.
21.
TartagliaMGelbBD. Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet2005;6:45–68.
22.
RobertsAEArakiTSwansonKD. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet2007;39:70–74.
23.
TartagliaMPennacchioLAZhaoC. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet2007;39:75–79.
24.
SchubbertSZenkerMRoweSL. Germline KRAS mutations cause Noonan syndrome. Nat Genet2006;38:331–336.
25.
FujikuraTFroelichL. Organ-weight/brain-weight ratios as a parameter of prenatal growth: a balanced growth theory of visceras. Am J Obstet Gynecol1972;112:896–902.
26.
PernotCWormsAMMarçonFGilgenkrantzSLeheupB. Le syndrome de Noonan et sa dysplasie cardio-vasculaire. A propos de 64 observations. Pediatie1989;44:437–447.
27.
SreeramNKitchinerDSmithA. Spectrum of valvar abnormalities in Noonan's syndrome—a pathologic study. Cardiol Young1994;4:62–66.
28.
BendonRWSiddiqiTde Courten-MyersGDignanP. Recurrent developmental anomalies: 1. Syndrome of hydranencephaly with renal aplastic dysplasia; 2. Polyvalvular developmental heart defect. Am J Med Genet Suppl1987;3:357–365.
29.
ChenBBronsonRTKlamanLD. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet2000;24:296–299.
30.
CartaCPantaleoniFBocchinfusoG. Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet2006;79:129–135.
31.
BraceR. Effects of outflow pressure on fetal lymph flow. Am J Obstet Gynecol1989;160:494–497.
32.
SasagawaINakadaTKubotaYSawamuraTTatenoTIshigookaM. Gonadal function and testicular histology in Noonan's syndrome with bilateral cryptorchidism. Arch Androl1994;32:135–140.
33.
OkuyamaANishimotoNYoshiokaT. Gonadal findings in cryptorchid boys with Noonan's phenotype. Eur Urol1981;7:274–277.
34.
McKayDBenirschkeKCurtisG. Infants of diabetic mothers histologic and histochemical observations on the pancreas. Obstet Gynecol1953;2:133–138.
35.
BarresiGInferreraCDe LucaF. Eosinophilic pancreatitis in the newborn infant of a diabetic mother. Virchows Arch A Pathol Anat Histol1978;380:341–348.
