Increased nuchal translucency: diagnostic value of RASopathy‐disorder testing

Xu, Lili; Li, D.‐Z.

doi:10.1002/uog.21954

Cited by 1 publication

(1 citation statement)

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“…NS is the most frequently reported monogenic disease in association with increased NT; pathogenic variants in RASopathy genes have been found in up to 20% of euploid fetuses with increased NT or other structural anomalies or both (Croonen et al, 2013; Leach et al, 2019; Sinajon et al, 2020; Stuurman et al, 2019). Currently, there is a consensus to perform RASopathy‐disorder (RD) testing in euploid fetuses with NT ≥ 3.5 mm (99th centile) associated with other features suggestive of NS, such as lymphatic or cardiac anomalies and polyhydramnios; however, RD testing in cases with isolated increased NT at the first trimester screening remains debatable (Sinajon et al, 2020; Stuurman et al, 2019; Xu & Li, 2020).…”

Section: Introductionmentioning

confidence: 99%

First prenatal case of Noonan syndrome with SOS2 mutation: Implications of early diagnosis for genetic counseling

Gentile

Fanelli

Lepri

et al. 2021

American J of Med Genetics Pt A

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RASopathies are a group of syndromes with partially overlapping clinical features caused by germline mutations of the RAS/MAPK signaling pathway genes. The most common disorder is Noonan syndrome (NS; MIM 163950). We report the first prenatal case of NS with SOS2 (NM_006939.4) mutation in a euploid fetus with a severe increase in nuchal translucency (NT > 12 mm). Trio‐based custom next‐generation sequencing detected a de novo heterozygous missense mutation in the SOS2 gene: c.800 T > A (p.Met267Lys). Owing to the marked variable expressivity of NS and the scarcity of SOS2 mutation‐related NS cases reported in the literature, it is difficult to provide appropriate genetic counseling. Several issues such as the best management technique and optimal NT cutoff have been discussed. In addition, in general, the fine balance between the advantages of an early prenatal diagnosis and the challenge of determining if the detected gene variant is pathogenic and, primarily, the stress of the counselees when providing a genetic counseling with limited information on the prenatal phenotype have been discussed. A prenatal path comprising examinations and multidisciplinary counseling is essential to support couples in a shared decision‐making process.

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