Table 1.
Clinical data, morphological, cytogenetic and molecular findings
| Features | Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 |
|---|---|---|---|---|---|---|---|---|
| Gravida/para | II/0 | IV/I | II/I | II/0 | I/0 | ND | III/II | I/0 |
| Gest. weeks/outcome | 3rd trimester (PROM) | liveborn (S) | 3rd trimester (CS) |
3rd trimester (TP) |
2nd trimester (IUFD) |
2nd trimester (TP) |
2nd trimester (TP) |
2nd trimester (TP) |
| Weight | 2136 g | 3000 g | 1560 g | 1020 g | 21.8 g | 350 g | 362 g | 630 g |
| Length (CHL) | 49.3 cm | 50 cm | 41 cm | 39 cm | 11.3 cm | 22.5 cm | 24.3 cm | 29.8 cm |
| Prenatal US | normal | normal | Possible oesophageal atresia, no TOF |
VACTERL association |
omphalocele sympodia |
CCAM | CHAOS | CHAOS and defect of left hand |
| Polyhydramnios | + | − | + | − | − | Oligohydr. | − | − |
| Hydrops | − | − | − | − | − | + | + | + |
| Tracheal malformation | TAG + BOF | TAG + BOF | TAG + BOFs | TAG +BOF | TAG + BOF |
TAT cranial segment |
TAT caudal segment |
TAT caudal segment |
|
Pulmonary hyperplasia, lung weight in grams (times the norm for GA) |
− 32.5 (0.96) |
− n.d |
− 27.0 (0.89) |
− 21.1 (0.83) |
− 0.72 (0.2) |
+ 17.9 (2.5) |
+ 41.6 (5.8) |
+ 58.0 (5.5) |
| Lung lobes (right/left) | 2/2 | 3/3 | 2/2 | 2/2 | 2/2 | 3/2 | 3/2 | 3/2 |
| Disease entity/associated malformations | isolated TAG complex |
TAG complex with right descend. aorta |
VACTERL including AA, cardiac VSD, TAG, OF and right RLRD |
VACTERL incl. SVD, ARA, card.-vasc. PLSVC, ARSA, TAG, OF, R(A)D, and right RLRD |
VACTERL variant incl. SVD, ARA, cardiac AVSD, TAG, OF, RA, right RLRD, AG, omphalocele and sympodia |
CHAOS and double left ureter, strangulating amniotic band |
CHAOS and agenesis of corpus callosum |
CHAOS and VSD, transverse defect of the left hand |
| BOF/TOF with Floyd classif.a | 2 | 2 |
2+ “bronchus suis” |
2 | 2 | NA | NA | NA |
| BOF/TOF with Faro classif.b | C | C |
C+ “bronchus suis” |
C | C | G | G | G |
|
VACTERL Evans subgroupc |
NA | NA | 3 | 4 | 4 | NA | NA | NA |
| Family history/Consanguinity | −/− | −/− | −/− | −/− | −/− | −/− | −/− | −/− |
| Karyotype | 46,XN | 46,XN | 46,XN | 46,XN | 46,XN | 46,XN | 46,XN | 46,XN |
| CNV analysis (aCGH and/or ES) |
− (aCGH and ES) |
ND |
− (aCGH and ES) |
− (ES only) |
− (aCGH and ES) |
ND |
− (aCGH and ES) |
− (aCGH and ES) |
| Singleton- or Trio-ES/Result |
Trio VUS in MAPK11 (de novo) |
ND |
Singleton − |
Singleton − |
Trio − |
ND |
Singleton − |
Singleton − |
aCGH array comparative genomic hybridisation, A(R)A ano(rectal) atresia, AG absent external genitalia, ARSA aberrant right subclavian artery, AVSD atrioventricular septal defect (persistent AV canal), (B)OF (broncho)oesophageal fistula, CCAM congenital cystic adenomatoid malformation of lungs, CHL crown-heel length; CS caesarean section; ES exome sequencing; GA gestational age; IUFD intrauterine fetal demise; NA not applicable; ND not determined; PLSVC persistent left superior vena cava, PROM premature rupture of membranes, RA renal agenesis, R(A)D renal(a)dysplasia, RLRD radial (longitudinal) limb reduction defect, S spontaneous birth, SVD sacral vertebral defects, TAG tracheal agenesis, TAT tracheal atresia, TLRD transverse limb reduction defect, TP termination of pregnancy, US ultrasound, VSD ventricular septal defect, VUS variant of unknown significance
aFloyd et al. [8]
bFaro et al. [9]
cEvans et al. [1]