Table 1.
Clinical features of individuals with DOT1L variants
| Proband | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|
| DOT1L variant (NM_032482.3) | c.133T>G (p.Cys45Gly) | c.299C>T (p.Thr100Met) | c.367G>A (p.Glu123Lys) | c.367G>A (p.Glu123Lys) | c.367G>A (p.Glu123Lys) | c.385G>A (p.Glu129Lys) | c.1876C>G (p.Leu626Val) | c.2557C>T (p.Arg853Cys) | c.3074A>T (p.Lys1025Met) |
| Inheritance | de novo | de novo | unknown | de novo | de novo | de novo | de novo | de novo | de novo |
| Sex | male | female | male | male | female | male | male | male | male |
| Age at last assessment | 5 years | 4 years 4 months (age at death) | 4 months (later died in infancy) | 5 years | 3 years 11 months | 6 years | 7 years | 4 years | 21 years |
| Medical history | |||||||||
| Brain anomalies (MRI/CT) | cortical dysplasia, periventricular heterotopia | no | HIE | bilateral brain atrophy, bilateral frontotemporal extra brain space widening, multiple small cysts in the corpus callosum | ONH/tract truncated corpus callosum | enlarged VRS, tentorial herniation | normal brain MRI | bilateral brain atrophy, focal cortical dysplasia | cerebellar atrophy, megalencephaly |
| Cardiac anomalies | ASD, PLSVC | myocarditis with cardiomyopathy; resolved by 1 year old | large VSD, moderate size ASD/PDA | ASD | no | no | VSD | no | no |
| Hypotonia | yes | yes | yes | no | yes | yes | no | no | no |
| Musculoskeletal anomalies | hip subluxation | hyperflexible hip joints | tall vertebral bodies, anomalous ribs (first 3), non ossified patella | N/D | hip laxity | no | pain after physical exercise, low endurance | N/D | no |
| Urogenital anomalies | hypospadias with chordee | no | hypospadias | cryptorchidism | grade 1 VUR | no | small penis | no | no |
| Hearing loss | sensorineural and conductive; stenosis external auditory canal | lack of reaction to loud stimuli or startle responses at 9 months | no | mild hearing loss in both ears | no | no | sensorineural w/ bilateral SCC dysplasia | no | no |
| Growth and development | |||||||||
| Global developmental delay | severe | yes | severe | severe | severe | severe | yes | mild | yes |
| Language | non-verbal | non-verbal | N/A (died in infancy) | only a few words | non-verbal | only a few words | only a few words | only a few words | only a few words |
| Stature (percentile) | short (2.94%) | short (4.95%) | N/D | N/D | normal (93.3%) | short (0.64%) | short (0.40%) | N/D | normal (39.7%) |
| Microcephaly (percentile) | no (97%) | no (60%) | yes (<3.0%) | N/D | yes (4.0%) | yes (3.0%) | yes (<1.0%) | yes (N/D) | no (>99%) |
Abbreviations are as follows: HIE, hypoxic ischemic encephalopathy; ONH, optic nerve hypoplasia; VRS, Virchow Robin spaces; ASD, atrial septal defect; PLSVC, persistent left supervior vena cava; VSD, ventricular septal defect; PDA, patent ductus arteriosus; VUR, vesicoureteral reflux; SCC, semi-circular canal; N/D, no data.