TY - JOUR
T1 - The fetal phenotype of noonan syndrome caused by severe, cancer-related PTPN11 variants
AU - Malniece, Ieva
AU - Grasmane, Adele
AU - Inashkina, Inna
AU - Stavusis, Janis
AU - Kreile, Madara
AU - Miklasevics, Edvins
AU - Gailite, Linda
N1 - Funding Information:
Riga Stradi?? University Internal grants We thank the parents for consenting to the publication of these case reports.
Publisher Copyright:
© Am J Case Rep, 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/31
Y1 - 2020/7/31
N2 - BACKGROUND The nuchal translucency measurement is the major focus of an early fetal ultrasound scan, with the goal to identify various inherited conditions, such as chromosomal aberrations and others. The diagnostic strategy for fetuses with increased nuchal translucency and normal karyotype is not clearly defined and may vary between countries. CASE REPORT We describe 2 cases of Noonan syndrome diagnosed prenatally by ultrasound scanning and genetic testing. The prenatal ultrasound scans showed abnormal nuchal translucencies, cystic lymphangioma/cystic hygroma, and other findings. Both fetuses had normal karyotype; however, after additional analysis, pathogenic variants of the PTPN11 gene (encoding SH2 domain-containing protein tyrosine phosphatase) were found, previously frequently described as somatic variants in hematological malignancies in postnatal life, but not previously described with severe prenatal phenotype of Noonan syndrome. CONCLUSIONS Our case reports confirm the hypothesis that severe, cancer related PTPN11 variants cause severe Noonan syndrome prenatal phenotype, when inherited in the germline.Analysis of pathogenic variants associated with Noonan syndrome should be included in the prenatal diagnostics for fetuses with increased nuchal translucency and normal karyotype.
AB - BACKGROUND The nuchal translucency measurement is the major focus of an early fetal ultrasound scan, with the goal to identify various inherited conditions, such as chromosomal aberrations and others. The diagnostic strategy for fetuses with increased nuchal translucency and normal karyotype is not clearly defined and may vary between countries. CASE REPORT We describe 2 cases of Noonan syndrome diagnosed prenatally by ultrasound scanning and genetic testing. The prenatal ultrasound scans showed abnormal nuchal translucencies, cystic lymphangioma/cystic hygroma, and other findings. Both fetuses had normal karyotype; however, after additional analysis, pathogenic variants of the PTPN11 gene (encoding SH2 domain-containing protein tyrosine phosphatase) were found, previously frequently described as somatic variants in hematological malignancies in postnatal life, but not previously described with severe prenatal phenotype of Noonan syndrome. CONCLUSIONS Our case reports confirm the hypothesis that severe, cancer related PTPN11 variants cause severe Noonan syndrome prenatal phenotype, when inherited in the germline.Analysis of pathogenic variants associated with Noonan syndrome should be included in the prenatal diagnostics for fetuses with increased nuchal translucency and normal karyotype.
KW - MeSH Lymphangioma, Cystic
KW - Noonan Syndrome
KW - Nuchal Translucency Measurement
KW - SH2 Domain-Containing Protein Tyrosine Phosphatases
KW - Lymphangioma, Cystic
UR - http://www.scopus.com/inward/record.url?scp=85089122529&partnerID=8YFLogxK
U2 - 10.12659/AJCR.922468
DO - 10.12659/AJCR.922468
M3 - Article
C2 - 32794475
AN - SCOPUS:85089122529
SN - 1941-5923
VL - 21
SP - e922468-1-e922468-6
JO - American Journal of Case Reports
JF - American Journal of Case Reports
M1 - e922468
ER -