IllnessPrenatally abnormal nuchal transparency, differential diagnosis

NGS +

[Sanger]

According to the Fetal Medicine Foundation, increased nuchal translucency (NT; >95th percentile based on crown-rump length) is found in 5% of fetuses. The incidence of chromosomal abnormalities increases exponentially with NT thickness. However, fetuses with increased NT are not only associated with a higher incidence of aneuploidy, fetal death and malformations, but also >150 genetic syndromes can cause thickened nuchal folds. After initial exclusion of chromosomal aneuploidy and large copy number variations, the few unselected, large-scale studies found >8-20% abnormal sequence variations in affected fetal DNAs compared with parental DNAs (included variants "VUS3" [of unknown significance] at the upper limit of the range span). Therefore, a negative result does not represent any exclusion of the clinical diagnosis.

Reference: https://pubmed.ncbi.nlm.nih.gov/30712880/

• Alias: (Generalised) fetal edema
• Alias: Fetal hydrops + ansarca
• Alias: Hydrops fetalis, non immune
• Alias: Nuchal hygroma
• Alias: Prenatally unusually thick nuchal transparency
• Allelic: Hemangioma, capillary infantile, somatic (FLT4)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Cardiofaciocutaneous syndrome 4 (MAP2K2)
• Congenital heart defects, multiple types, 7 (FLT4)
• Costello syndrome (HRAS)
• Fabry disease (GLA)
• Farber lipogranulomatosis (ASAH1)
• GM1-gangliosidosis, type I, II, III (GLB1)
• Galactosialidosis (CTSA)
• Gaucher disease, perinatal lethal + Gaucher disease, type I, II, III, IIIC (GBA)
• Glycogen storage disease IV (GBE)
• Hennekam lymphangiectasia-lymphedema syndrome 1 (CCBE1)
• Hydrops fetalis, cystic hygroma, hydropic placenta [panelapp] (NMNAT2)
• Immunodysregulation, polyendocrinopathy, enteropathy, XL (FOXP3)
• Lymphatic malformation 1 (FLT4)
• Lymphedema-distichiasis syndrome (FOXC2)
• Mucolipidosis II alpha/beta + III alpha/beta (GNPTAB)
• Mucopolysaccharidosis IVA (GALNS)
• Mucopolysaccharidosis VII (GUSB)
• Mucopolysaccharidosis type IVB [Morquio] (GLB1)
• Nephrotic syndrome, type 14 (SGPL1)
• Noonan syndrome 2 + 10 (LZTR)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome 7 (BRAF)
• Noonan syndrome-like disorder (CBL)
• Sialidosis, type I + II (NEU1)
• Wolman disease (LIPA)