Targeted ultrasound examination and DNA testing for Noonan syndrome, in fetuses with increased nuchal translucency and normal karyotype

Abstract

Objective To define sonographic criteria that may improve the prenatal diagnosis of Noonan syndrome by targeted DNA testing.Methods We searched our Fetal Medicine Unit records for all cases with a final diagnosis of Noonan syndrome. A literature review was undertaken to identify the sonographic features of Noonan syndrome fetuses. Information was pooled to define the most common features.Results In our database, we identified three cases of Noonan syndrome. The diagnosis was suspected prenatally in two of them. Thirty-nine cases were identified in the literature. In the presented cases we show that suspicion of Noonan syndrome should arise when, after an increased nuchal translucency, ultrasound investigation in the second trimester shows a persistant nuchal fold (NF) or cystic hygroma in combination with at least one of the following features: hydrops fetalis, pleural effusion, cardiac anomalies, polyhydramnios or specific facial abnormalities. ConclusionPrenatal ultrasound findings in Noonan syndrome can be subtle and aspecific, but when specific characteristics are present additional targeted DNA analysis is indicated.

Orbital lymphaticovenous malformations: Current and future treatments

“…Cystic hygroma is a malformation associated with Down syndrome, Turner syndrome, and Noonan syndrome, suggesting a genetic cause. 7,43,149 In addition, VEGFR-3 mutations in both recessive and dominant patterns have been shown to cause lymphedema and lymphatic malformations. 44,66 Mutations in the SOX18 gene in humans are also associated with recessive and dominant hypo-trichosis-lymphedema-telangiectasia.…”

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings

“…Part of the positive cases have been described in case reports. 24,27 Ultrasound findings considered as indication for prenatal sequencing were increased NT (greater than the 95th percentile (p95)), cystic hygroma, distended JLS, ascites, hydrops fetalis, pleural effusion, polyhydramnios, CHD and renal abnormalities.…”

“…[17][18][19] Prenatal features of NS are increased nuchal translucency (NT), distended jugular lymphatic sacs (JLS), cystic hygroma, hydrops fetalis, pleural effusion, polyhydramnios, CHD and renal abnormalities. [20][21][22][23][24] The first prenatal DNA diagnosis of NS in a fetus with massive cystic hygroma, pleural effusion and ascites showed a mutation in the PTPN11 gene. 25 Lee et al 26 performed a retrospective review of prenatal PTPN11 testing.…”

First Trimester Diagnosis of Holoprosencephaly Secondary to a Ring Chromosome 7

“…HPE is a phenotypically variable disorder with heterogeneous etiology including both genetic and environmental causes. Numerical and structural chromosomal abnormalities account for up to 68% of prenatally detected HPE [4], while single gene defects (e.g., MIM 142945) and environmental factors underlie most of the remaining cases. The estimated prevalence of HPE in liveborn children is less than 1/10,000, but the incidence may be as high as 1/250 in first trimester conceptuses [5].…”