Table 2.
Characteristic of submicroscopic variants detected from 20 fetuses with AAA and normal karyotype
| Case number | Ultrasound findings (group) | CMA results | Size | Associated syndrome | Parental inheritance | Pathogenicity classification | Outcome |
|---|---|---|---|---|---|---|---|
| Variants of clinical significance | |||||||
| 1 | RAA with mirror-image branching (group A) |
17p11.2 (16,615,982_18,922,171) × 3 |
2.3 Mb | Potocki-Lupski syndrome (# 610883) | De novo | Pathogenic | TOP |
| 2 | RAA-ALSA, VSD, U-shaped vascular rings (group C) |
22q11.21 (18,648,855_21,800,471) × 1 |
3.1 Mb | DiGeorge syndrome (# 611867) | De novo | Pathogenic | TOP |
| 3 | RAA-ALSA, pulmonary atresia, VSD, PLSVC, thymus dysplasia, overriding aorta (group C) |
22q11.21 (18,648,855_21,800,471) × 1 |
3.1 Mb | DiGeorge syndrome (# 611867) | De novo | Pathogenic | TOP |
| 4 | RAA, right ventricular stenosis, pulmonary stenosis (group C) |
1q21.1q21.2 (145,995,176_147,398,268) × 3 |
1.4 Mb | 1q21.1 duplication syndrome (# 612475) | – | Likely pathogenic | TOP |
| 5 | ARSA, echogenic intracardiac focus, mild tricuspid regurgitation (group B) |
22q11.21 (18,919,477_21,800,471) × 1 |
2.8 Mb | DiGeorge syndrome (# 611867) | De novo | Pathogenic | TOP |
| 6 | ARSA, PLSVC, FGR (group C) |
15q11.2 (22,770,421_23,277,436) × 1 |
507 Kb | None | De novo | Likely pathogenic | TOP |
| 7 | ARSA, strephenopodia (group C) |
17p12p11.2 (15,759,453_20,547,625) × 3 |
4.7 Mb | Potocki-Lupski syndrome (# 610883) | De novo | Pathogenic | TOP |
| 8 | ARSA, VSD, PLSVC, Blake’s porch cyst (group C) |
2q13 (111,397,196_113,111,856) × 1 |
1.7 Mb | None | Maternal | Likely pathogenic | Live born, normal development |
| 9 | CoA, VSD, increased spine curvature, FGR (group C) |
5q22.3q23.1 (113,627,122_116,240,273) × 1 |
2.6 Mb | 8q21.11 deletion syndrome (# 614230) | – | Pathogenic | Stillbirth |
|
8q21.11q21.13 (74,350,927_81,710,386) × 1 |
7.3 Mb | ||||||
| 10 | CoA, FGR (group C) |
7q11.23 (72,713,282_74,154,209) × 1 |
1.4 Mb | Williams-Beuren syndrome (# 194050) | De novo | Pathogenic | TOP |
| 11 | CoA, hypoplastic left heart syndrome, VSD, PLSVC (group C) |
8q23.1q23.2 (106,364,168_110,798,080) × 1 |
4.4 Mb | None | De novo | Pathogenic | TOP |
| 12 | CoA, VSD (group C) |
18q23 (73,969,018_78,013,728) × 1 |
4.0 Mb | None | – | Pathogenic | TOP |
|
22q13.33 (49,571,996_51,197,766) × 3 |
1.6 Mb | ||||||
| 13 | CoA, interrupted aortic arch, VSD (group C) |
22q11.21 (18,631,364_21,800,471) × 1 |
3.1 Mb | DiGeorge syndrome (# 611867) | De novo | Pathogenic | TOP |
| 14 | CoA, the oval valve bulges, small left heart (group C) |
22q11.21 (18,649,189_21,800,471) × 3 |
3.1 Mb | 22q11 duplication syndrome (# 608363) | De novo | Likely pathogenic | TOP |
| 15 | CoA, PLSVC, FGR (group C) |
2p25.3p11.2 (50,813_87,053,152) hmz |
87 Mb, | None | – | Pathogenic | Live born, normal development |
|
2q11.1q37.3 (95,550,957_242,773,583) hmz |
147 Mb | ||||||
| 16 | CoA, VSD, renal dysplasia, FGR (group C) |
16q23.2q24.3 (79,800,878_90,146,366) hmz |
10.3 Mb | None | – | Pathogenic | TOP |
|
16p13.3p12.3 (94,807_19,302,326) hmz |
19.2 Mb | ||||||
| Variants of non-clinical significance | |||||||
| 17 | RAA with mirror-image branching, VSD, overriding aorta, pulmonary stenosis (group C) |
15q13.3 (32,003,537_32,444,043) × 3 |
441 kb | None | De novo | VOUS | TOP |
| 18 | ARSA, VSD, FGR (group C) |
4q24 (106,284,925_107,545,257) × 3 |
1.3 Mb | None | De novo | VOUS | Premature birth, normal development |
| 19 | ARSA (group A) |
7q34 (139,340,641_139,769,640) × 3 |
429 kb | None | Maternal | Likely benign | Live born, normal development |
| 20 | CoA, VSD (group C) |
10q21.1 (59,095,330_60,684,488) × 1 |
1.5 Mb | None | Maternal | Likely benign | Live born, died after 20 days |
AAA aortic arch abnormalities, ARSA aberrant right subclavian artery, CMA chromosomal microarray analysis, CoA coarctation of the aorta, FGR fetal growth restriction, PLSVC persistent left superior vena cava, RAA right aortic arch, RAA-ALSA right aortic arch with aberrant left subclavian artery, TOP termination of pregnancy, VOUS variants of unknown significance, VSD ventricular septal defect