Table 1.
Clinical Features of Individuals with Heterozygous DLL1 Pathogenic Variants
| Individual | 1 (F1/II-1) | 2 (F2/II-4) | 3 (F2/II-1) | 4 (F2/II-2) | 5 (F2/I-2) | 6 (F3/II-1) | 7 (F4/II-1) | 8 (F5/II-1) | 9 (F6/II-1) | 10 (F7/II-1) | 11 (F8/II-1) | 12 (F9/II-1) | 13 (F10/II-1) | 14 (F11/II-1) | 15 (F12/II-1) | Summary of Clinical Features |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gender | f | f | m | m | f | m | m | f | m | m | f | f | m | f | m | 7f/8 m |
| Age at last visit | 3 y | 2 y | 4 y | 5 y | u | 8 y | 16 y | 2 y | 2 y | 9 y | 7 y | 35 y | 33+2 w | 8 y | 3 y | birth-35 y |
| DD/ID (HP:0012758 / HP:0001249) | + | − | − | + | + | + | + | + | + | + | + | + | NA | + | + | 12/14 |
| ASD (HP:0000729) | − | − | + | u | u | − | + | − | + | + | + | − | NA | − | + | 6/14 |
| ADHD (HP:0007018) | − | u | u | u | u | + | + | − | − | + | − | − | NA | − | − | 3/14 |
| Stereotypic behavior (HP:0000733) | − | ND | ND | ND | ND | − | − | + | (+) | − | (+) | − | NA | − | + | 4/14 |
| Seizures (HP:0001250) | − | u | u | u | u | + | + | − | − | − | + | + | NA | + | + | 6/14 |
| Muscular hypotonia (HP:0001252) | + | ND | ND | ND | ND | + | − | − | (+) | + | + | − | NA | − | + | 6/14 |
| Ataxia (HP:0001251) | + | ND | ND | ND | ND | + | − | − | − | − | − | + | NA | − | + | 4/14 |
| Abnormal brain MRI (HP:0012443) | + | + | + | ND | ND | + | + | + | + | ND | + | + | + | + | − | 11/15 |
| Ventriculomegaly (HP:0002119) | + | − | + | ND | ND | + | − | mild | mild | ND | + | mild | + | − | − | 8/15 |
| Hydrocephalus (HP:0000238) | − | + | + | ND | ND | + | − | − | − | ND | − | − | − | − | − | 3/15 |
| Abnormal corpus callosum (HP:0001273) | − | − | − | ND | ND | + | + | + | + | ND | + | − | − | + | − | 6/15 |
| Cortical dysplasia (HP:0002539) | − | − | − | ND | ND | − | (+) | + | − | ND | − | − | − | (+) | − | 3/15 |
| Migration defect (HP:0002269) | − | − | − | ND | ND | − | − | − | − | ND | − | PVNH | − | − | − | 1/15 |
| Other brain abnormality | − | − | + | ND | ND | + | − | − | + | ND | − | − | − | + | − | 4/15 |
| Abnormal prenatal brain imaging | + | + | u | u | u | + | − | + | − | − | + | − | + | − | − | 6/15 |
| Abnormal vertebrae (HP:0003468) | ND | ND | ND | ND | ND | sc | sc, ky | sc, ky, sd | ND | ND | sc | ND | − | ND | ND | 4/15 |
| Microcephaly (HP:0000252) | − | ND | ND | ND | ND | − | − | − | − | + | − | − | − | ND | + | 2/15 |
| Macrocephaly (HP:0000256) | − | ND | ND | ND | ND | + | − | − | − | − | − | − | − | ND | − | 1/15 |
| Facial dysmorphism (HP:0000271) | (+) | + | ND | ND | ND | − | + | + | + | + | + | − | + | − | − | 8/15 |
| Other (details in Table S1) | + | + | + | + | − | + | + | + | + | + | + | + | − | − | + | 12/15 |
| Type of sequence variant | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | nonsense | splice site | splice site | missense | deletion | |
| Inheritance | de novo | affected mother | affected mother | affected mother | u | affected father | u | u | de novo | de novo | not maternal | de novo | de novo | de novo | de novo |
Abbreviations: F, family; f, female; m, male; y, years; w, weeks of gestation; DD, developmental delay; ID, intellectual disability; ASD, autism spectrum disorder; ADHD, attention deficit hyperactivity disorder; NA, not applicable; ND, not determined; u, unknown; PVNH, periventricular nodular heterotopia; (+), subtle/borderline; +, present; −, absent; sc, scoliosis; ky, kyphosis; SD, segmentation defect.