Clinical characteristics of the subjects with ADARB1 variants
| Family 1 (Iraq) | Family 2 (Egypt) | Tan et al10 (Caucasian, Hispanic, Azari) | ||
| Pt 1 (IV-7) | Pt 2 (III-1) | Pt 3 (III-2) | 4 pts, 4 families | |
| Age at last FU, sex | 5.6 y, F | 6 y, F | 4.9 y, F | Mean 5.2 y, 4 M |
| Alive | + | + | + | + (3), one died at 2 y |
| Consanguinity | + | + | + | + (2) |
| Previous miscarriages | + | – | – | + (1) |
| Similarly affected siblings | + (2, deceased) | + (III-2) | + (III-1) | – |
| Pregnancy | Regular (38 we) | Regular (40 we) | Regular (38 we) | Regular (3), pre-eclampsia (1) |
| Birth complications | – | – | – | – |
| OFC at birth | N/A | 33.3 cm (−0.72 SD) | 33 cm (−0.7 SD) | 0.38 to −2.2 SD (2 N/A) |
| Neonatal course | ||||
| Irritability | + | + | + | N/A |
| Excessive crying | + | + | + | N/A |
| Developmental history | ||||
| Visual tracking | Poor | – | – | – (3) |
| Head control | – | – | – | – (3) |
| Sit with support | – | – | – | – (3) |
| Standing with support | – | – | – | – (3) |
| Walking with support | – | – | – | – (4) |
| Speech | – | – | – | – (3), few words (1) |
| Intellectual disability | Profound | Profound | Profound | Profound (2), severe (2) |
| Feeding difficulties | + | + | + | + (4) |
| Dysmorphic features | + | + | + | + (2) |
| OFC at last FU | 45 cm (−4.3 SD) | 43 cm (−5.8 SD) | 43 cm (−5.1 SD) | −3.3 to −4.4 SD (mean −3.8 SD) |
| Neurological features | ||||
| Axial hypotonia | + | + | + | + (4) |
| Spastic tetraplegia | + | + | + | + (2) |
| Hyperreflexia | + | + | + | + (1) |
| Sleep disturbance | + | – | – | + (1) |
| Other | Bruxism, insomnia | – | – | Tremor (1), staring spells (1), repetitive movements (1) |
| Vision | ||||
| Strabismus | + | + | + | + (1) |
| Other | – | Cortical blindness | Cortical blindness | Cortical blindness (3) |
| ABRs | N/A | Normal | Normal | Normal (4) |
| Epilepsy | ||||
| Onset | 15 d | 4 mo | 5 mo | 2–7 mo (mean 4.3) |
| Type | MCS, GTCS, IS | TS, MCS | TS, MCS | FS, TS, GS, GTCS |
| Frequency, duration | Daily, 0.5–2 min | Daily, 1–3 min | Daily, 1–3 min | Weekly to daily |
| Associated signs | Apnoea, staring | Head deviation, vomiting | Head deviation | Eye deviation, twitching, apnoea |
| EEG | MFDs, slow background | MFDs | Bilateral TPDs | MFDs, slow background |
| Status epilepticus | – | – | – | + (2) |
| Response to AEDs* | – | – | – | – (4) |
| Evolution | GTCS (LGS) | TS, MCS | TS, MCS | GTCS |
| Current status | Intractable | Intractable | Intractable | Intractable |
| Neuroimaging features† | ||||
| Diffuse cerebral atrophy | + | + | + | + (3), temporal lobes (1) |
| White matter loss | + | + | + | + (2) |
| Delayed myelination | – | + | + | + (2) |
| CCH | + | + | + | + (3) |
| Enlarged ventricles | + | + | + | + (3) |
| Basal ganglia T2-weighted hyperintensity | – | + | – | - (3) |
| Other features | Contractures, muscle wasting, 2 hypopigmented spots on the sternum | PDA | – | Laryngomalacia (1), plagiocephaly (2), cryptorchidism (1), contractures and muscle wasting (1) |
| Metabolic investigations‡ | Normal | Normal | Normal | Normal (4) |
*AEDs included clonazepam, levetiracetam, phenytoin, topiramate, valproate and vigabatrin.
†MRI pictures of three out of four patients were available for review.
‡Extended metabolic screening including organic acid in urine, acylcarnitine profile, ammonia and lactate.
ABRs, auditory brain responses; AEDs, antiepileptic drugs; CCH, corpus callosum hypoplasia; d, days; EEG, electroencephalogram; F, female; FS, focal seizures; FU, follow-up; GS, generalised seizures; GTCS, generalised tonic-clonic seizures; IS, infantile spasms; LGS, Lennox-Gastaut syndrome; M, male; MCS, myoclonic seizures; MFDs, multifocal discharges; mo, months; N/A, not available; OFCS, occipitofrontal circumference; PDA, patent ductus arteriosus; Pts, patients; s, syndrome; TPDs, temporoparietal discharges; TS, tonic seizures; we, weeks; y, years.