Table 2.
Diagnostic variants identified after trio ES and review in fetuses presenting with initially isolated increased NT at 11–14 weeks of gestation
| Study ID | NT (mm) | Additional findings at presentation | Findings at later scans | Variant(s) | ACMG class |
|---|---|---|---|---|---|
| Fetuses with initially isolated increased NT, then other anomalies detected later | |||||
| PP2904 | 9.5 | None | Hydrops; ASD | EPHB4 c.759dupC p.(Ser254Glnfs*10) [De novo Het]** | LP |
| PP1726 | 8.0 | None | Narrowing of aorta, suspected coarctation | TAB2 c.1311_1312delTC p.(Pro438Glnfs*2) [De novo Het]** | LP |
| PP0503 | 4.5 | None | AVSD | PTPN11 c.922A>G p.(Asn308Asp) [Mat]** | P |
| PP0692 | 6.0 | None | Short limbs, polyhydramnios | RAF1 c.786T>G p.(Asn262Lys) [De novo Het] | LP |
| PP1864 | 7.4 | None | Hypoplastic left heart syndrome with DORV, TGA, PA | KMT2D c.673+1G>A [De novo Het]** | LP |
| PP2033 | 6.5 | None | Hypoplastic left heart syndrome with DORV | CHD7 c.656dupG p.(Leu220Profs*67) [De novo Het]** | LP |
| PP1462 | 8.9 | None | Short femurs; cystic dilatation of lymphatics from neck to upper chest; bilateral RPD | BRAF c.770A>G p.(Gln257Arg) [De novo Het]** | P |
| PP1807 | 4.7 | None | Hypoplastic right heart; VSD | MID1 c.1102C>T p.(Arg368*) [De novo Hemi]** | P |
| Fetal0116 | N/S | None |
Hydrocephalus; hyperflexed feet NB: Couple had previous pregnancies similarly affected |
FLVCR2 c.1509+1G>A (splice variant) [Mat]** FLVCR2 c.1001dupT p.(Met334Ilefs*37) [Pat]** |
LP LP |
| Fetal0222 | 5.2 | None | Pleural effusion; ascites | SOS1 c.1132A>G p.(Thr378Ala) [Pat]** | P |
| Fetal0307 | 4.7 | None | Shones complex | NR2F2 c.1091delT p.(Leu364Cysfs*15) [De novo Het] | P |
| Fetal0385 | 4.7 | None | Short long bones; flattened facies; short nasal bone; ambiguous genitalia | FGD1 c.2026_2028delGAG p.(Glu676del) [Mat Hemi] | LP |
| Fetuses with initially isolated increased NT which remained isolated or resolved later in pregnancy | |||||
| PP0602 | 4.8 | None | None | Chr15 UPD [Mat]** | N/A |
| Fetal0045 | 3.5 | None | None | RERE c.248dupA p.(Ser84Valfs*4) [De novo Het]** | LP |
| Fetuses presenting with initially isolated increased NT where later pregnancy follow up was not possible | |||||
| PP3321 | 9.9 | None | N/A (ToP) | PTPN11 c.214G>A p.(Ala72Thr) [De novo Het] | LP |
| PP2039 | 6.2 | None | N/A (IUD) | NIPBL c.1435C>T p.(Arg479*) [De novo Het]** | P |
ACMG, American College of Medical Genetics and Genomics; ASD, atrial septal defect; AVSD, atrioventricular septal defect; DORV, double outlet right ventricle; Hemi, hemizygous; Het, heterozygous; IUD, in utero death; LP, likely pathogenic; Mat, maternal; N/A, not applicable; N/S, not specified; P, pathogenic; PA, pulmonary atresia; Pat, paternal; RPD, renal pelvis dilatation; TGA, transposition of great arteries; ToP, termination of pregnancy; UPD, uniparental disomy; VSD, ventricular septal defect.
**Variants previously published.