Table 1.
Main clinical features among individuals with (likely) pathogenic KDM6B variants
|
Feature |
PTVs N = 73a |
PAVs N = 12 |
p value (PTVs vs. PAVs) |
Total N = 85a(%) |
|---|---|---|---|---|
| Sex (males/total) | 51/72 | 10/12 | 0.50 | 61/84 (73%) |
| Growth | ||||
| Increased birth weight [>2 SD] | 10/50 | 0/8 | 0.33 | 10/58 (17%) |
| Increased weight [>2 SD] | 9/56 | 0/8 | 0.59 | 9/64 (14%) |
| Tall stature [>2 SD] | 5/58 | 0/8 | 1.0 | 5/66 (8%) |
| Macrocephaly [>2 SD] | 15/57 | 2/8 | 1.0 | 17/65 (26%) |
| At least one feature of overgrowth | 18/59 | 3/10 | 1.0 | 21/69 (30%) |
| Neurodevelopmental and psychiatric issues | ||||
| Language/speech delay | 63/66 | 9/11 | 0.15 | 72/77 (94%) |
| Motor delay | 56/63 | 10/11 | 1.0 | 66/74 (89%) |
| ID or learning problems | 37/56 | 3/8 | 0.14 | 40/64 (63%) |
| ASD | 38/65 | 8/11 | 0.51 | 46/76 (61%) |
| Behavior problems, non-ASD | 40/65 | 4/8 | 0.70 | 44/73 (60%) |
| Psychotic disorders [≥12 years old] | 4/18 | 0/2 | 1.0 | 4/20 (20%) |
| Neurological issues | ||||
| Seizures | 9/62 | 0/7 | 0.58 | 9/69 (13%) |
| Sleep disturbances | 21/59 | 0/7 | 0.09 | 21/66 (32%) |
| Movement disorder/gait disturbances/hypertonia/ataxia | 15/59 | 1/8 | 0.67 | 16/67 (24%) |
| Hypotonia | 36/63 | 4/6 | 1.0 | 40/70 (57%) |
| Gastrointestinal issues | ||||
| Neonatal feeding difficulties or gastroesophageal reflux | 29/58 | 4/7 | 1.0 | 33/65 (51%) |
| Constipation | 10/55 | 1/6 | 1.0 | 11/61 (18%) |
| Congenital anomalies | ||||
| Congenital heart disease | 8/57 | 0/7 | 0.58 | 8/64 (13%) |
| Cleft lip/palate/uvula | 1/60 | 2/7 | 0.03b | 3/67 (4%) |
| Genitourinary abnormalities | 6/55 | 0/7 | 1.0 | 6/62 (10%) |
| Musculoskeletal and limb abnormalities | ||||
| Joint hypermobility | 24/56 | 2/6 | 1.0 | 26/62 (42%) |
| Scoliosis/kyphosis/lordosis | 8/57 | 0/7 | 0.58 | 8/64 (13%) |
| Syndactyly | 4/58 | 2/8 | 0.15 | 6/66 (9%) |
| Short fingers or toes | 6/57 | 0/7 | 1.0 | 6/64 (9%) |
| Broad fingers/fingertips/hands/toes/feet | 12/58 | 1/7 | 1.0 | 13/65 (20%) |
| Sensory issues | ||||
| Myopia/amblyopia | 20/54 | 0/7 | 0.08 | 20/61 (33%) |
| Strabismus | 8/57 | 0/7 | 0.58 | 8/64 (13%) |
| Hearing loss | 1/55 | 0/7 | 1.0 | 1/62 (2%) |
| Recurrent ear infections | 7/54 | 0/5 | 1.0 | 7/59 (12%) |
PTVs, protein-truncating variants; PAVs, protein-altering variants (only [likely] pathogenic variants included); ID, intellectual disability; ASD, autism spectrum disorder; SD, standard deviation.
a
Single individual with a second pathogenic variant in HNRNPU was not included in the calculations.
b
Not significant after correction for multiple testing.