Table 1. Baby Bambi Cohort Demographic Characteristics and Rapid Trio Genome Sequencing Results.
| Characteristic | Total (N = 130) | Diagnosed (n = 65)a | Possible diagnosis (n = 15)b | Undiagnosed (n = 50)c | P value |
|---|---|---|---|---|---|
| Sex | |||||
| Male | 70 (54) | 34 (52) | 9 (60) | 27 (54) | >.99 |
| Female | 60 (46) | 31 (48) | 6 (40) | 23 (46) | |
| Gestational age | |||||
| Full term | 53 (41) | 29 (45) | 8 (53) | 16 (32) | .26 |
| Preterm | 46 (35) | 21 (32) | 4 (27) | 21 (42) | |
| Unknown | 31 (24) | 15 (23) | 3 (20) | 13 (26) | |
| Ethnicityd | |||||
| Jewish | 67 (51) | 28 (43) | 7 (47) | 32 (64) | .04 |
| Non-Jewish | 58 (45) | 36 (55) | 7 (47) | 15 (30) | |
| Mixed | 5 (4) | 1 (2) | 1 (6) | 3 (6) | |
| Outcome | |||||
| Deceased | 29 (22) | 14 (22) | 3 (20) | 12 (24) | .87 |
| Alive | 78 (60) | 40 (61) | 10 (67) | 28 (56) | |
| No data | 23 (18) | 11 (17) | 2 (13) | 10 (20) | |
| Primary category inclusion criteria | |||||
| Primary neurologic phenotypee | 35 (27) | 18 (28) | 4 (27) | 13 (26) | .55 |
| 2 Separate major anomalies | 47 (36) | 23 (36) | 6 (40) | 18 (36) | |
| Single otherwise rare abnormality | 14 (11) | 9 (14) | 1 (6) | 4 (8) | |
| Structural brain malformation | 14 (11) | 8 (13) | 0 | 6 (12) | |
| Unstable metabolic or endocrine abnormality | 12 (9) | 5 (8) | 4 (27) | 3 (6) | |
| Congenital heart failure or cardiomyopathy | 6 (5) | 2 (1) | 0 | 4 (8) | |
| Undefinedf | 2 (1) | 0 | 0 | 2 (4) | |
| Genomic variants (n = 80) | |||||
| Chromosomal abnormalities | 13 (10) | 12 (18) | 1 (7)f | 0 | NA |
| Common aneuploidyg | 3 (2) | 3 (4) | 0 | 0 | |
| Copy-number abnormalities | 8 (6) | 7 (11) | 1 (7) | 0 | |
| Unbalanced translocation | 2 (2) | 2 (3) | 0 | 0 | |
| Single-nucleotide variants | 65 (50) | 51 (78) | 14 (93) | 0 | |
| Triplet repeat expansion | 1 (1) | 1 (2) | 0 | 0 | |
| Uniparental heterodisomyh | 1 (1) | 1 (2) | 0 | 0 | |
| Inheritance | |||||
| Autosomal recessive | 28 (21) | 22 (34) | 6 (40)i | 0 | NA |
| De novo, sporadic | 24 (18) | 23 (36) | 1 (7) | 0 | |
| Autosomal dominant familial | 10 (8) | 5 (8) | 5 (32) | 0 | |
| X-linked recessive | 2 (2) | 1 (2) | 1 (7) | 0 | |
| X-linked dominant | 2 (2) | 1 (2) | 1 (7) | 0 | |
| Dual diagnosis | 1 (1) | 1 (2) | 0 | 0 | NA |
| Suspected dual diagnosis | 13 (10) | NA | NA | 0 | NA |
| Secondary findings (n = 112)j | 7 (63) | 4 (7) | 1 (8) | 2 (4) | .74 |
| TAT, mean (SD) [range], d | |||||
| Rapid report | 7.4 (2.7) [2-18] | 6.5 (2.3) [2-15] | 8.5 (3.3) [4-16] | 8.2 (2.8) [2-18] | .003 |
| Final report | 67.6 (26.1) [23-212] | 69.6 (28.9) [24-212] | 57.3 (22.4) [23-98] | 68.2 (23.0) [23-111] | .22 |
Abbreviation: TAT, turnaround time.
Disease-causing variant identified.
Variants of unknown significance in gene highly suspected to fully or partially explain phenotype identified.
Negative genome sequencing test.
Overall, 23 of 113 parents (58 of 113 were diagnosed; 55 of 113 had variants of unknown significance or were undiagnosed) were consanguineous; 17 parents did not have consanguinity ruled out or confirmed. By ethnicity, there was 1 consanguineous couple with Jewish ethnicity (negative rapid trio genome sequencing results), 22 consanguineous couples with non-Jewish ethnicity (14 with disease-causing variants identified, 3 with variants of unknown significance, and 5 with negative rapid trio genome sequencing results), and 0 consanguineous couples with mixed ethnicity. The difference among groups was not significant (P = .11).
Primary neurologic phenotype included encephalopathy, seizures, and severe hypotonia.
See eTable 2 in Supplement 2.
Trisomy 21 and trisomy 18 (eTable 2 in Supplement 2).
Prader-Willi syndrome detected by methylation-specific multiplex ligation-dependent probe amplification; see Discussion and eTable 2 in Supplement 2.
Including novel candidate gene.
Data regarding secondary findings are valid for 112 of 130 patients (18 opted out on consent form: 11 in the diagnosed group; 2 in the variants of unknown significance group; 5 with negative results).