Background
Methods
Participants
Participants with nested 22q11.2 duplications or deletions
Region | Number | % de novoa
| Age mean (sd) | Age range (years) | % male |
---|---|---|---|---|---|
Total | 46 | 60% | 10.8(10.1) | 0.8–39 | 52% |
AB/AC deletion group | 15 | 86% | 8.9(4.2) | 2–15 | 53% |
A-B deletion | 11 | 80% | 7.8(3.8) | 2–15 | 55% |
A-C deletion | 4 | 100% | 11.8(4.4) | 5–14 | 50% |
BD/CD deletion group | 18 | 69% | 11.1(10.7) | 1–38 | 50% |
B-D deletion | 14 | 77% | 10.4(9.0) | 1–38 | 43% |
C-D deletion | 4 | 33% | 13.6(16.9) | 0.8–36 | 75% |
BD/CD duplication group | 10 | 13% | 14.5(15.2) | 1–39 | 60% |
B-D duplication | 8 | 0% | 16.5(16.6) | 1–39 | 63% |
C-D duplication | 2 | 50% | 6.5(2.0) | 5–7 | 50% |
A-B duplicationb
| 1 | Unknown | 7.0 | – | 0% |
E-F duplicationb
| 2 | 0% | 6.6(2.8) | 4–8 | 50% |
Region | Number | % de novoa
| Age mean (sd) | Age range (years) | % male |
---|---|---|---|---|---|
AB/AC deletion group | 13 | 83% | 10 (4.2) | 5–18 | 54% |
A-B deletion | 10 | 78% | 8.9 (3.6) | 5–15 | 60% |
A-C deletion | 3 | 100% | 13.7 (4.8) | 9–18 | 33% |
BD/CD deletion group | 12 | 50% | 14.2 (12.7) | 3–42 | 50% |
B-D deletion | 8 | 57% | 13.4 (12.1) | 4–42 | 38% |
C-D deletion | 4 | 33% | 15.9 (15.5) | 3–37 | 75% |
BD/CD duplication group | 9 | 14% | 16.9 (14.7) | 5–39 | 56% |
B-D duplication | 7 | 0% | 19.4 (15.9) | 5–39 | 57% |
C-D duplication | 2 | 50% | 8 (4.1) | 5–11 | 50% |
Total | 34 | 55% | 13.3 (11.0) | 3–42 | 53% |
Region | Number |
n ASD (male) | % de novoa
| Age mean (sd) | Age range (years) | % male |
---|---|---|---|---|---|---|
AB/AC deletion group | 12 | 5(3) | 90% | 10.0 (4.4) | 5–18 | 58% |
A-B deletion | 9 | 4(3) | 90% | 8.7 (3.7) | 5–15 | 67% |
A-C deletion | 3 | 1(0) | 100% | 13.7 (4.8) | 9–18 | 33% |
BD/CD deletion group | 8 | 0 | 60% | 10.5 (4.8) | 5–18 | 25% |
B-D deletion | 6 | 0 | 70% | 10.2 (3.8) | 6–17 | 17% |
C-D deletion | 2 | 0 | 0% | 11.6 (9.1) | 5–18 | 50% |
Classic AD duplication | 29 | 7(5) | 67% | 7.1 (3.4) | 2–13 | 75% |
BD/CD duplication group | 5 | 1(0) | 30% | 12.7 (10.4) | 5–31 | 60% |
B-D duplication | 3 | 1(0) | 0% | 15.8 (13.1) | 7–31 | 67% |
C-D duplication | 2 | 0 | 50% | 8.0 (4.1) | 5–11 | 50% |
Comparison cohorts
Procedures
Medical record and developmental history review
ASD diagnostic classification
Neuropsychiatric questionnaires
Analysis
Results
Higher rates of ASD when LCR-A to B involved
Moderately lower adaptive and social functioning when AB region involved
Number | Mean (SD) |
d
| 95% confidence interval | |
---|---|---|---|---|
SRS-2 T score | 50 (10) | |||
BD/CD deletion | 9 | 53.4 (13.6) | ||
AB/AC deletion | 10 | 68.5 (15.7) | 1.01 | (− 0.07, 2.11) |
Classic deletion | 61 | 63.0 (12.6) | − 0.41 | (− 1.11, 0.27) |
BD/CD duplication | 6 | 59.5 (16.6) | ||
Classic duplication | 28 | 64.0 (16.3) | 0.27 | (− 0.67, 1.22) |
SCQ raw total | Cutoff 15 | |||
BD/CD deletion | 7 | 5.7 (4.9) | ||
AB/AC deletion | 8 | 15.0 (9.3) | 1.20 | (− 0.11, 2.52) |
Classic deletion | 52 | 10.8 (7.3) | − 0.54 | (− 1.32, 0.23) |
BD/CD duplication | 4 | 7.2 (9.5) | ||
Classic duplication | 22 | 12.4 (10.3) | 0.50 | (− 0.67, 1.68) |
Vineland composite | 100(15) | |||
BD/CD deletion | 5 | 103.8 (19.6) | ||
AB/AC deletion | 10 | 85.7 (24.0) | − 0.79 | (− 2.11, 0.52) |
Classic deletion | 57 | 87.1 (15.9) | 0.08 | (− 0.61, 0.78) |
BD/CD duplication | 6 | 92.6 (18.7) | ||
Classic duplication | 27 | 89.4 (19.4) | − 0.16 | (− 1.11, 0.78) |
Vineland communication | 100(15) | |||
BD/CD deletion | 5 | 106.0 (21.7) | ||
AB/AC deletion | 10 | 83.0 (18.5) | − 1.17 | (− 2.55, 0.20) |
Classic deletion | 58 | 89.7 (18.1) | 0.36 | (− 0.32, 1.06) |
BD/CD duplication | 6 | 92.1 (20.2) | ||
Classic duplication | 27 | 91.2 (18.5) | − 0.04 | (− 0.99, 0.90) |
Vineland daily living | 100(15) | |||
BD/CD deletion | 5 | 96.4 (14.6) | ||
AB/AC deletion | 10 | 86.9 (26.2) | − 0.40 | (− 1.69, 0.87) |
Classic deletion | 57 | 88.4 (15.1) | 0.08 | (− 0.60, 0.78) |
BD/CD duplication | 6 | 91.8 (23.0) | ||
Classic duplication | 28 | 93.6 (21.2) | 0.08 | (− 0.86, 1.02) |
Vineland socialization | 100(15) | |||
BD/CD deletion | 5 | 107.6 (19.6) | ||
AB/AC deletion | 10 | 91.0 (27.4) | − 0.65 | (− 1.96, 0.65) |
Classic deletion | 57 | 90.1 (16.5) | − 0.04 | (− 0.74, 0.64) |
BD/CD duplication | 6 | 98.1 (18.3) | ||
Classic duplication | 27 | 90.8 (21.2) | − 0.35 | (− 1.30, 0.60) |
CASI ADHD | ||||
BD/CD deletion | 2 | 2.5 (1.3) | ||
AB/AC deletion | 7 | 3.4 (1.4) | 0.63 | (− 1.56, 2.83) |
Classic deletion | 43 | 2.7 (1.2) | − 0.52 | (− 1.36, 0.32) |
BD/CD duplication | 4 | 2.7 (2.1) | ||
Classic duplication | 20 | 2.8 (1.3) | 0.09 | (− 1.09, 1.27) |
CASI anxiety | ||||
BD/CD deletion | 2 | 1.3 (0.7) | ||
AB/AC deletion | 7 | 1.9 (1.1) | 0.49 | (− 1.68, 2.67) |
Classic deletion | 43 | 2.3 (1.3) | 0.30 | (− 0.53, 1.14) |
BD/CD duplication | 4 | 1.9 (1.5) | ||
Classic duplication | 20 | 1.8 (1.6) | − 0.05 | (− 1.24, 1.12) |
CASI ASD | ||||
BD/CD deletion | 1 | n/a | ||
AB/AC deletion | 4 | 1.0 (1.0) | n/a | n/a |
Classic deletion | 37 | 0.5 (0.4) | − 0.83 | (− 1.94, 0.27) |
BD/CD duplication | 4 | 0.6 (0.4) | ||
Classic duplication | 16 | 0.8 (0.8) | 0.26 | (− 0.98, 1.50) |
CASI Schizoaffective | ||||
BD/CD deletion | 1 | n/a | ||
AB/AC deletion | 3 | 0.5(0.5) | n/a | n/a |
Classic deletion | 6 | 0.5(0.2) | − 0.09 | (− 0.78, 0.61) |
BD/CD duplication | 0 | n/a | ||
Classic duplication | 4 | 0.5(0.2) | n/a | n/a |
CASI behav. regulation | ||||
BD/CD deletion | 2 | 0.9 (0.4) | ||
AB/AC deletion | 7 | 0.9 (0.6) | 0.06 | (− 2.08, 2.21) |
Classic deletion | 43 | 1.0 (0.6) | 0.16 | (− 0.67, 1.00) |
BD/CD duplication | 4 | 0.3 (0.3) | ||
Classic duplication | 20 | 1.0 (0.8) | 0.78 | (− 0.42, 2.00) |
CASI Depression | ||||
BD/CD deletion | 2 | 0.4 (0) | ||
AB/AC deletion | 7 | 0.6 (0.7) | 0.33 | (− 1.82, 2.50) |
Classic deletion | 43 | 0.5 (0.7) | − 0.15 | (− 0.99, 0.67) |
BD/CD duplication | 4 | 0.2 (0.4) | ||
Classic duplication | 20 | 0.4 (0.4) | 0.48 | (− 0.70, 1.68) |
Increased rates of psychiatric disorders
Total (n) | No eval | Had eval | GDD | Lang Dx | ADHD | ID | ODD | OCD | Anxiety | MDD | |
---|---|---|---|---|---|---|---|---|---|---|---|
AB/AC deletion | 13 | 7.7% | 92.3% | 30.8% | 0.0% | 53.8% | 0.0% | 7.7% | 23.1% | 23.1% | 0.0% |
A-B deletion | 10 | 10% | 90% | 30% | 0% | 50% | 0% | 10% | 20% | 20% | 0% |
< 3 yrs | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
3–14 yrs | 8 | 0 | 8 | 2 | 0 | 4 | 0 | 0 | 1 | 1 | 0 |
15+ yrs | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 |
A-C deletion | 3 | 0% | 100% | 33.3% | 0% | 66.7% | 0% | 0% | 33.3% | 33.3% | 0% |
3–14 yrs | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
15+ yrs | 2 | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 0 |
BD/CD deletion | 12 | 33.3% | 66.7% | 16.7% | 8.3% | 8.3% | 25% | 8.3% | 25% | 25% | 0% |
B-D deletion | 8 | 12.5% | 87.5% | 37.5% | 0% | 12.5% | 12.5% | 0% | 0% | 25% | 25% |
< 3 yrs | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
3–14 yrs | 5 | 0 | 5 | 3 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
15+ yrs | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
C-D deletion | 4 | 75% | 25% | 0% | 0% | 25% | 0% | 25% | 25% | 25% | 25% |
< 3 yrs | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
15+ yrs | 2 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 |
BD/CD duplication | 9 | 33.3% | 66.6% | 22.2% | 0% | 0% | 44.4% | 0% | 11.1% | 11.1% | 11.1% |
B-D duplication | 7 | 42.9% | 57.1% | 28.6% | 14.3% | 28.6% | 0% | 0% | 0% | 14.3% | 14.3% |
< 3 yrs | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
3–14 yrs | 3 | 0 | 3 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 0 |
15+ yrs | 3 | 2 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
C-D duplication | 2 | 0% | 100% | 100% | 0% | 0% | 0% | 0% | 0% | 0% | 0% |
3–14 yrs | 2 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Total sample | 34 | 23.5% | 76.5% | 32.3% | 2.9% | 32.3% | 2.9% | 5.9% | 11.8% | 20.6% | 11.8% |
Higher rates of medical comorbidities
A to B deletion (n = 11) | A to C deletion (n = 4) | B to D deletion (n = 14) | B to D duplication (n = 8) | C to D deletion (n = 4) | C to D duplication (n = 2) | |
---|---|---|---|---|---|---|
Audiologic | ||||||
Audiogram | 11 | 4 | 14 | 8 | 4 | 2 |
Abnormal | 6 | 1 | 2 | 2 | 0 | 1 |
Abnormal Ratea
| 55% | 25% | 14% | 25% | 0% | 50% |
Abnormalities | CHL | CHL | SNHL | CHL, CSNHL | n/a | CHL |
Cardiac | ||||||
Echocardiogram | 9 | 4 | 11 | 5 | 2 | 1 |
Abnormal | 7 | 3 | 7 | 1 | 1 | 0 |
Abnormal Ratea
| 64% (78%) | 75% | 50% (64%) | 12% (20%) | 25% (50%) | 0% |
Abnormalities | Enlarged PA, VR, PS, TOF with PS, IAA with ARSCA, TR, PDA | TA, RAA with ALSCA, dilated aortic root, VR, ASD/VSD | Aortic root dilation, aneurism of TV, ASD, PDA, PFO, TA, VSD | PFO | TOF with pulmonary valve stenosis | n/a |
Endocrine | ||||||
Bloodwork | 11 | 4 | 14 | 4 | 4 | 1 |
Abnormal | 6 | 2 | 6 | 2 | 0 | 0 |
Abnormal Ratea
| 55% | 50% | 43% | 25% (50%) | 0% | 0% |
Abnormalities | Hypocalcemia hypothyroidism low vitamin D (each category n = 2) | Hypocalcemia | Hypocalcemia (n = 2), diabetes mellitus, borderline HbA1C, low growth factors, low vitamin D, hypothyroidism | Borderline abnormal thyroid function tests, neonatal hypoglycemia | n/a | n/a |
GI | ||||||
Symptom screen | 11 | 3 | 13 | 6 | 3 | 2 |
Abnormal | 7 | 2 | 12 | 5 | 1 | 2 |
Abnormal ratea
| 64% | 50% (67%) | 86% (92%) | 63% (83%) | 25% (33%) | 100% |
Abnormalities | GERD (n = 7), constipation (n = 4), anal atresia (n = 1), feeding tube (n = 2) | Constipation (n = 2), GERD | GERD (n = 11), constipation (n = 9), feeding tube (n = 4) | GERD (n = 4), eosinophilic esophagitis, feeding tube | GERD, chronic constipation | GERD (n = 2), constipation, feeding tube |
Hematologic | ||||||
CBC completed | 11 | 4 | 14 | 8 | 4 | 2 |
Cytopenias | 3 | 3 | 2 | 0 | 0 | 0 |
Abnormal Ratea
| 27% | 75% | 14% | 0% | 0% | 0% |
Immune | ||||||
Bloodwork | 9 | 4 | 11 | 4 | 4 | 2 |
Abnormal | 2 | 2 | 4 | 1 | 2 | 0 |
Abnormal Ratea
| 18% (22%) | 50% | 29% (36%) | 13% (26%) | 50% | 0% |
Abnormalities | Low Ig | Low Ig, T cell lymphopenia, inadequate vaccine titers | Low Ig (n = 2), absent thymus, inadequate vaccine response | Low Ig | Low Ig, recurrent MRSA infections, inadequate vaccine response | n/a |
Neurologic | ||||||
Seizures | 3 | 0 | 2 | 0 | 0 | 0 |
% reported | 27% | 0% | 14% | 0% | 0% | 0% |
MRI | 8 | 2 | 10 | 4 | 0 | 0 |
Abnormal MRI | 3 | 1 | 3 | 2 | n/a | n/a |
Abnormal Ratea
| 27% (38%) | 25% (50%) | 21% (30%) | 25% (50%) | 0% | 0% |
MRI findings | Chiari 1, white matter lesions, pachygyria | Minimal bilateral congenital optic nerve hypoplasia | Chiari 1, hypoplastic corpus callosum, polymicrogyria | Prominent ventricles, subarachnoid spaces, choroid plexus cysts | n/a | n/a |
Ophthalmologic | ||||||
Ophtho exam | 9 | 4 | 11 | 3 | 4 | 1 |
Abnormal | 3 | 2 | 5 | 1 | 0 | 0 |
Abnormal ratea
| 27% (33%) | 50% | 45% | 13% (33%) | n/a | n/a |
Abnormalities | Astigmatism, exophoria, nystagmus | Strabismus, minimal ONH | Anisocoria, iris coloboma, ONH nystagmus (n = 2), retinal detachment, strabismus (n = 3) | Amblyopia | n/a | n/a |
Palate | ||||||
Clinical eval. | 9 | 4 | 12 | 6 | 2 | 2 |
Abnormal | 8 | 3 | 4 | 1 | 0 | 1 |
Abnormal ratea
| 89% (73%) | 75% (27%) | 33% (29%) | 17% (13%) | 0% | 50% |
Abnormalities | SMCP (n = 3) VPI (n = 8) | SMCP (n = 1), VPI (n = 3) | SMCP (n = 2), VPI (n = 4) | High arched palate with small uvula | n/a | VPI |
Renal | ||||||
Ultrasound | 9 | 2 | 9 | 6 | 2 | 1 |
Abnormal | 3 | 0 | 1 | 4 | 1 | 0 |
Abnormal ratea
| 27% (33%) | 0% | 7% (11%) | 50% (67%) | 25% (50%) | 0% |
Abnormalities | Bilateral pelviectasis, nephrocalcinosis hydronephrosis | n/a | Medullary nephrocalcinosis | Duplicated collecting system, small kidneys (n = 3) | Solitary, low-lying kidney | n/a |
Spine | ||||||
Screening x-rays | 6 | 4 | 4 | 2 | 1 | 1 |
Abnormal | 6 | 3 | 2 | 1 | 1 | 0 |
Abnormal Ratea
| 55% (100%) | 38% (75%) | 14% (50%) | 13% (50%) | 25% (100%) | 0% |
Abnormalities | Hypoplastic vertebra (n = 2), vertebral fusion (n = 4), extra lumbar vertebra | Fusion of C2-C3, kyphoscoliosis, thickened spinous process of C2 | Scoliosis, C2-C3 fusion and dysmorphic dens, upswept C2 | Hemivertebra at T9, absent rib | 6 thoracic ribs and 6 lumbar vertebrae | n/a |