Table 1.
Clinical characteristics of ARID1B patients
| Total | ARID1B-CSS | ARID1B-ID | ||||||
|---|---|---|---|---|---|---|---|---|
| Clinical featuresd | n= 143 | % | n =79 | % | n =64 | % | p value | Test |
| Sex (female) | 143 | 48.3 | 79 | 57.0 | 64 | 37.5 | 0.028 | a |
| Growth parameters & development | ||||||||
| Gestational age, weeks (mean; SD) | 133 | 39.0; 2.1 | 75 | 39.1; 2.0 | 58 | 38.9; 2.4 | 0.879 | b |
| Birthweight (<–2 SDS) | 129 | 5.4 | 74 | 6.8 | 55 | 3.6 | 0.506 | c |
| Height at birth (<–2 SDS) | 43 | 9.3 | 27 | 11.1 | 16 | 6.3 | 0.660 | c |
| OFC at birth (<–2 SDS) | 51 | 3.9 | 35 | 2.9 | 16 | 6.3 | 0.232 | c |
| Age last measurements, years (median; min–max) | 143 | 10; 0–51 | 79 | 10; 0–36 | 64 | 9; 0.5–51 | 0.682 | b |
| Weight (<–2 SDS) | 92 | 6.5 | 46 | 8.7 | 46 | 4.3 | 0.571 | c |
| Height (<–2 SDS) | 122 | 30.3 | 70 | 37.1 | 52 | 21.2 | 0.177 | c |
| OFC (<–2 SDS) | 105 | 2.9 | 63 | 3.2 | 42 | 2.4 | 0.670 | c |
| Motor skills gross, delayed | 103 | 99.0 | 46 | 97.8 | 57 | 100.0 | 0.447 | c |
| Motor skills fine, delayed | 100 | 95.0 | 44 | 97.7 | 56 | 92.9 | 0.381 | c |
| Speech, delayed | 131 | 65.6 | 75 | 68.0 | 56 | 62.5 | 0.106 | c |
| Obstructive sleep apneae | 71 | 8.5 | 34 | 0.0 | 37 | 16.2 | 0.026 | c |
| Laryngomalaciae | 90 | 19.8 | 47 | 17.0 | 44 | 22.7 | 0.466 | a |
| Feeding difficulties | 121 | 69.4 | 62 | 62.9 | 59 | 76.3 | 0.111 | a |
| Start of feeding difficulties | 71 | 34 | 37 | 0.345 | c | |||
| Birth | 76.1 | 76.5 | 75.7 | |||||
| Before 6 months | 16.9 | 20.6 | 13.5 | |||||
| After 6 months | 7.0 | 2.9 | 10.8 | |||||
| Duration of feeding problems | 58 | 23 | 35 | 0.639 | c | |||
| Brief | 46.6 | 39.1 | 51.4 | |||||
| Several years | 6.9 | 8.7 | 5.7 | |||||
| Ongoing | 46.6 | 52.2 | 42.9 | |||||
| Tube feeding | 65 | 16.9 | 22 | 13.6 | 43 | 18.6 | 0.409 | c |
| 0–6 months | 10.8 | 4.5 | 14.0 | |||||
| 6–12 months | 3.1 | 4.5 | 2.3 | |||||
| 1–3 years | 1.5 | 0.0 | 2.3 | |||||
| Recurrent infections | 75 | 57.3 | 30 | 63.3 | 45 | 53.3 | 0.391 | a |
| Upper airway tract | 17.3 | 10.0 | 22.2 | |||||
| Lower airway tract | 2.7 | 0.0 | 4.4 | |||||
| ENT infections | 12.0 | 10.0 | 13.3 | |||||
| Otitis media | 14.7 | 13.3 | 15.6 | |||||
| Urinary tract | 2.7 | 3.3 | 2.2 | |||||
| Neurological features | ||||||||
| Intellectual disability | 127 | 99.2 | 70 | 98.6 | 57 | 100.0 | 0.015 | c |
| Normal–mild | 3.1 | 1.4 | 5.3 | |||||
| Mild | 28.3 | 38.6 | 15.8 | |||||
| Mild–moderate | 15.7 | 8.6 | 24.6 | |||||
| Moderate | 22.0 | 22.9 | 21.1 | |||||
| Moderate–severe | 16.5 | 17.1 | 15.8 | |||||
| Severe | 13.4 | 10.0 | 17.5 | |||||
| Hypotonia | 116 | 81.0 | 71 | 80.3 | 45 | 82.2 | 0.795 | a |
| Seizures | 142 | 27.5 | 78 | 28.2 | 64 | 26.6 | 0.880 | c |
| No seizures, but abnormal EEG | 5.6 | 6.4 | 4.7 | |||||
| Seizure frequency | 18 | 9 | 9 | 0.671 | c | |||
| Once | 27.8 | 11.1 | 44.4 | |||||
| Less than once a year | 11.1 | 22.2 | 0.0 | |||||
| Once a year | 33.3 | 44.4 | 22.2 | |||||
| Once a month | 11.1 | 11.1 | 11.1 | |||||
| 1/2 a month | 5.6 | 0.0 | 11.1 | |||||
| ≥2 per month | 5.6 | 0.0 | 11.1 | |||||
| Agenesis of the corpus callosum | 101 | 28.7 | 62 | 29.0 | 39 | 28.2 | 0.344 | c |
| Partial/hypoplasia | 13.9 | 17.7 | 7.7 | |||||
| Neuroradiology | 47 | 87.2 | 17 | 94.1 | 30 | 83.3 | 0.305 | a |
| Delayed myelination | 17.0 | 11.8 | 20.0 | |||||
| Mega cisterna magna | 14.9 | 23.5 | 10.0 | |||||
| Colpocephaly | 10.6 | 11.8 | 10.0 | |||||
| Hypoplasia | 4.3 | 0.0 | 6.7 | |||||
| Enlarged Virchow–Robin spaces | 4.3 | 5.9 | 3.3 | |||||
| Vision and hearing impairments | ||||||||
| Vision impaired | 109 | 48.6 | 62 | 45.2 | 47 | 53.2 | 0.406 | a |
| Vision problems | 68 | 70.6 | 33 | 78.8 | 35 | 62.9 | 0.320 | c |
| Astigmatism | 16.2 | 24.2 | 8.6 | |||||
| Strabismus | 30.9 | 36.4 | 25.7 | |||||
| Optic nerve hypoplasia | 2.9 | 6.1 | 0.0 | |||||
| Nystagmus | 8.8 | 6.1 | 11.4 | |||||
| Refraction error | 10.3 | 9.1 | 11.4 | |||||
| Myopia | 102 | 27.5 | 59 | 18.6 | 43 | 39.5 | 0.020 | a |
| Hypermetropia | 50 | 18.0 | 21 | 28.6 | 29 | 10.3 | 0.140 | c |
| Abnormal eye exam | 40 | 17.5 | 15 | 6.7 | 25 | 24.0 | 0.224 | c |
| Hearing loss | 122 | 22.1 | 71 | 18.3 | 51 | 27.5 | 0.157 | a |
| Hearing loss, conductive | 6.6 | 1.4 | 13.7 | |||||
| Hearing loss, bilateral | 11.5 | 8.5 | 15.7 | |||||
| Hearing loss, unilateral | 4.9 | 5.6 | 3.9 | |||||
| Eartubes | 4.9 | 4.2 | 5.9 | |||||
| Start hearing problems, congenital | 11 | 63.6 | 3 | 66.7 | 8 | 62.5 | 0.109 | c |
| Hearing aid | 5 | 80.0 | 2 | 100.0 | 3 | 66.7 | 0.665 | c |
| Dysmorphic features | ||||||||
| Coarse face | 121 | 81.8 | 62 | 90.3 | 59 | 72.9 | 0.013 | a |
| Hairline (low anterior and/or posterior) | 91 | 69.2 | 45 | 75.6 | 46 | 63.0 | 0.196 | a |
| Scalp hair, abnormal | 129 | 79.1 | 78 | 83.3 | 51 | 72.5 | 0.141 | a |
| Sparse | 58.1 | 62.8 | 51.0 | |||||
| Forehead (broad or narrow) | 95 | 42.1 | 49 | 28.6 | 46 | 56.5 | 0.000 | c |
| Broad | 22.1 | 6.1 | 39.1 | |||||
| Narrow | 20.0 | 22.4 | 17.4 | |||||
| Eyelashes, long | 131 | 63.4 | 79 | 75.9 | 52 | 44.2 | 0.000 | a |
| Eyebrows, thick | 134 | 81.3 | 78 | 91.0 | 56 | 67.9 | 0.001 | a |
| Ptosis | 133 | 20.3 | 77 | 20.8 | 56 | 19.6 | 0.872 | a |
| Tear duct nonfunctioning or absent | 93 | 15.1 | 54 | 16.7 | 39 | 12.8 | 0.609 | a |
| Nasal bridge, abnormal | 100 | 61.0 | 59 | 62.7 | 41 | 58.5 | 0.050 | a |
| Wide | 34.0 | 40.7 | 24.4 | |||||
| Flat | 21.0 | 20.3 | 22.0 | |||||
| Broad | 12.0 | 5.1 | 22.0 | |||||
| Nasal tip, abnormal | 129 | 76 | 53 | 0.002 | a | |||
| Broad | 58.1 | 61.8 | 52.8 | |||||
| Upturned (anteverted nares) | 29.5 | 39.5 | 15.1 | |||||
| Nose, abnormal | 83 | 47.0 | 43 | 53.5 | 40 | 40.0 | 0.022 | a |
| Short | 26.5 | 39.5 | 12.5 | |||||
| Long | 20.5 | 14.0 | 27.5 | |||||
| Alae nasi, thick | 107 | 55.1 | 69 | 66.7 | 38 | 34.2 | 0.001 | a |
| Nasal base, broad | 88 | 48.9 | 48 | 43.8 | 40 | 55.0 | 0.392 | a |
| Philtrum, abnormal | 109 | 78.9 | 72 | 86.1 | 37 | 64.9 | 0.001 | a |
| Short | 24.8 | 29.2 | 16.2 | |||||
| Long | 44.0 | 48.6 | 35.1 | |||||
| Broad | 34.9 | 44.4 | 16.2 | |||||
| Mouth, large | 131 | 68.7 | 75 | 76.0 | 56 | 58.9 | 0.037 | a |
| Upper vermillion, abnormal | 127 | 56.7 | 75 | 60.0 | 52 | 51.9 | 0.366 | a |
| Thin | 35.4 | 45.3 | 21.2 | |||||
| Thick | 21.3 | 14.7 | 30.8 | |||||
| Lower vermillion, thick | 125 | 69.6 | 76 | 78.9 | 49 | 55.1 | 0.005 | a |
| Lower lip, drooping | 71 | 56.3 | 30 | 76.7 | 41 | 41.5 | 0.004 | a |
| Cleft palate/submucous cleft | 90 | 6.7 | 35 | 14.3 | 55 | 1.8 | 0.031 | a |
| Cleft palate | 2.2 | 5.7 | 0.0 | |||||
| Bifid uvula | 2.2 | 5.7 | 0.0 | |||||
| Submucous cleft | 3.3 | 5.7 | 1.8 | |||||
| High arched palate | 85 | 16.5 | 31 | 22.6 | 54 | 13.0 | 0.250 | a |
| Ears, abnormal | 122 | 52.5 | 66 | 57.6 | 56 | 46.4 | 0.433 | a |
| Low-set | 9.8 | 13.6 | 5.4 | |||||
| Posterior rotated | 7.4 | 9.1 | 5.4 | |||||
| Hypertrichosis | 128 | 86.7 | 76 | 94.7 | 52 | 75.0 | 0.001 | a |
| Musculoskeletal anomalies | ||||||||
| Scoliosis | 123 | 26.0 | 70 | 27.1 | 53 | 24.5 | 0.743 | a |
| Pectus, excavatum | 104 | 13.5 | 57 | 14.0 | 47 | 12.8 | 0.850 | a |
| Primary dentition, delayed | 65 | 44.6 | 40 | 50.0 | 25 | 36.0 | 0.313 | a |
| Permanent dentition, delayed | 33 | 48.5 | 18 | 33.3 | 15 | 66.7 | 0.056 | a |
| Widely spaced teeth | 72 | 41.7 | 40 | 40.0 | 32 | 43.8 | 0.748 | a |
| Bone age, delayed | 40 | 47.5 | 30 | 46.7 | 10 | 50.0 | 1.000 | c |
| Joint laxity | 88 | 60.2 | 52 | 61.5 | 36 | 58.3 | 0.763 | a |
| Early arthritis | 75 | 5.3 | 36 | 5.6 | 39 | 5.1 | 1.000 | c |
| Clinodactyly | 77 | 36.4 | 42 | 45.2 | 35 | 25.7 | 0.076 | a |
| Short phalanges | 49 | 34.7 | 34 | 41.2 | 15 | 20.0 | 0.151 | a |
| Complete absent or small 5th distal phalanx | 110 | 40.0 | 66 | 60.6 | 44 | 9.1 | 0.000 | c |
| Prominent distal phalanges; | 102 | 24.5 | 64 | 31.3 | 38 | 13.2 | 0.040 | a |
| Prominent interphalangeal joints | 103 | 21.4 | 64 | 28.1 | 39 | 10.3 | 0.032 | a |
| Brachydactyly general | 60 | 16.7 | 19 | 15.8 | 41 | 17.1 | 1.000 | c |
| Brachydactyly fifth finger | 68 | 30.9 | 22 | 50.0 | 46 | 21.7 | 0.018 | a |
| Small nails | 122 | 54.9 | 73 | 68.5 | 49 | 34.7 | 0.000 | a |
| Which nails, 5th finger and/or toe | 106 | 55.7 | 67 | 65.7 | 39 | 38.5 | 0.007 | a |
| Which nails, all | 53 | 11.3 | 29 | 20.7 | 24 | 0.0 | 0.027 | c |
| Fetal finger pads | 100 | 29.0 | 50 | 26.0 | 50 | 32.0 | 0.509 | a |
| Intestinal | ||||||||
| Inguinal hernia | 90 | 7.8 | 46 | 2.2 | 44 | 13.6 | 0.056 | c |
| Intestinal problems | 105 | 48.6 | 60 | 36.7 | 45 | 64.4 | 0.000 | a |
| Constipation | 30.5 | 21.7 | 42.2 | |||||
| Gastroesophageal reflux | 17.1 | 13.3 | 22.2 | |||||
| Diarrhea | 4.8 | 3.3 | 6.7 | |||||
| Pyloric Stenosis | 2.9 | 5.0 | 0.0 | |||||
| Umbilical hernia | 4.8 | 1.7 | 8.9 | |||||
| Cardiac & genitourinary anomalies | ||||||||
| Cardiac anomalies | 113 | 19.5 | 69 | 21.7 | 44 | 15.9 | 0.492 | a |
| ASD | 10.6 | 13.0 | 6.8 | |||||
| VSD | 5.3 | 5.8 | 4.5 | |||||
| Renal anomalies | 95 | 12.6 | 53 | 11.3 | 42 | 14.3 | 0.666 | c |
| Renal sonography, abnormal | 43 | 25.6 | 19 | 21.1 | 24 | 29.2 | 0.105 | c |
| Cryptorchidism | 65 | 55.4 | 28 | 39.3 | 37 | 67.6 | 0.023 | a |
| Endocrinological abnormalities e | ||||||||
| Diabetes mellitus | 71 | 7.0 | 43 | 7.0 | 28 | 7.1 | 1.000 | c |
| Type 2 diabetes mellitus | 4 | 75.0 | 2 | 100.0 | 2 | 50.0 | 1.000 | c |
| Age (years) diagnosis (min–max) | 2 | 18–46 | 1 | 18.0 | 1 | 46.0 | 0.317 | b |
| Hypothyroidism | 63 | 19.0 | 38 | 15.8 | 25 | 24.0 | 0.417 | a |
| Age (years) diagnosis (median; min–max) | 10 | 8; 1–40 | 4 | 4; 1.3–36.0 | 6 | 6; 1.0–40.0 | 0.394 | b |
| Growth hormone deficiency | 51 | 13.7 | 33 | 18.2 | 18 | 5.6 | 0.398 | c |
| Growth hormone supplementation | 50 | 12.0 | 31 | 16.1 | 19 | 5.3 | 0.387 | c |
| Behavioral characteristics | ||||||||
| Behavioral abnormalities | 71 | 83.1 | 28 | 85.7 | 43 | 81.4 | 0.945 | a |
| Hyperkinetic | 15.5 | 14.3 | 16.3 | |||||
| Short attention | 25.4 | 25.0 | 25.6 | |||||
| Impulsiveness | 14.1 | 14.3 | 14.0 | |||||
| Obsessive | 15.5 | 14.3 | 16.3 | |||||
| Rigid | 8.5 | 3.6 | 11.6 | |||||
| Anger outbursts | 16.9 | 10.7 | 20.9 | |||||
| Aggressive | 16.9 | 14.3 | 18.6 | |||||
| Anxious | 23.9 | 17.9 | 27.9 | |||||
| Poor sociability | 19.7 | 17.9 | 20.9 | |||||
| Hyperactivity | 63 | 42.9 | 25 | 60.0 | 38 | 31.6 | 0.026 | a |
| High pain thresholde | 47 | 40.4 | 28 | 28.6 | 19 | 57.9 | 0.044 | a |
| Psychiatric disorders | ||||||||
| ADHD | 48 | 33.3 | 16 | 50.0 | 32 | 25.0 | 0.083 | a |
| Autistic traits | 77 | 57.1 | 27 | 66.7 | 50 | 52.0 | 0.215 | a |
| Malignancies | 97 | 1.0 | 53 | 0.0 | 44 | 2.3 | 0.454 | c |
Only characteristics present in ≥5% of all patients or in either patient group, characteristics differing between groups, and distinctive features are shown.
ADHD attention deficit hyperactivity disorder, ARID1B-CSS patient group with a suspicion of Coffin–Siris syndrome before genetic testing, ARID1B-ID patient group with no suspicion of Coffin–Siris syndrome before genetic testing, ASD atrial septal defect, CSS Coffin–Siris syndrome, EEG electroencephalography, ENT ear nose throat, OFC occipitofrontal circumference, SDS standard deviation score, VSD ventricular septal defect.
aChi-square.
bMann–Whitney U.
cFisher’s.
dThe total number of a feature can differ from the sum of subcategories, because in some cases it was possible to answer with more than one option or to report the existence of a feature without specifying.
eData regarding these features were collected through email after first analyses.