Clinical manifestations of 14 patients from eight families resulting from UBE3A mutation
| AS | Familial | Sporadic | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 1 | 2 | 3 | |||||||||
| Mutation site (exon) | 9 | 12 | 16 | 9 | 15 | 8 | 16 | 10 | ||||||||
| Sequence change | 2037del10 | 2527insA | 3033insA | 1461del14 | 2992ins3 | 645A | 3086ins5 | 2530del26insA | ||||||||
| Pedigree No | III.1 | III.2 | III.1 | III.2 | IV.8 | IV.14 | III.2 | III.3 | III.4 | V.2 | V.10 | III.1 | III.1 | III.2 | ||
| Sex | F | M | F | F | M | F | M | M | F | F | M | M | M | M | ||
| Age at diagnosis (y) | 3.9 | <1 | 7 | 4 | 14 | 33 | 20 | 18 | 28 | 22 | 21 | 2 | 11 | 8 | ||
| Age at last review | 8 | 5 | 11 | 7 | 17 | 36 | 23 | 20 | 31 | 27 | 26 | 8 | 12 | 15 | ||
| Feeding difficulty | + | − | + | − | − | − | − | − | − | − | − | + | − | − | ||
| Onset of walking (mth) | 32 | 30 | 36 | 24 | 19 | 20 | 24 | 60 | 36 | 42 | 36 | 42 | 24 | 48 | ||
| Ataxia | +/− | +/− | +/− | +/− | + | + | +/− | +/− | +/− | ++ | ++ | + | +/− | ++ | ||
| Seizures | + | + | + | − | + | + | + | − | − | + | + | + | + | + | ||
| Onset of seizures (y) | 4 | 3.5 | 5 | − | 1/2 | 2 | 20 | − | − | 2 | 2.5 | 2 | 7 | 8 | ||
| Persistent or recurrent seizures | − | − | − | − | − | + | + | − | − | − | + | − | − | + | ||
| Treatment | VA | VA | VA | − | − | VA | BZP | − | − | VA | VA/ BZP | VA | VA | VA | ||
| Cortical myoclonus | + | − | + | + | + | ++ | ++ | + | ++ | + | ++ | + | + | ++ | ||
| First abnormal EEG recorded (y) | 4 | 3 | 1.5 | 1.5 | 1.5 | 2 | 5 | 3 | 6 | 2 | 2.5 | 2.5 | 6 | 2 | ||
| Sleep disturbance | + | + | − | + | − | + | + | − | − | + | + | + | + | + | ||
| Language (number of words) | 5 | 4 | 4 | 6 | 10 | 3 | 2 | 2 | 2 | 6 | 2 | 5 | 5 | 10 | ||
| Sign language | + | + | + | + | + | − | + | + | + | + | + | + | + | + | ||
| Happy disposition | + | + | + | + | + | + | + | + | + | + | + | + | + | + | ||
| Hyperexcitability | + | + | + | + | + | + | + | + | + | + | + | + | + | + | ||
| Laughter when excited | + | + | + | + | + | + | + | + | + | + | + | + | + | + | ||
| Hand flapping when excited | + | + | + | + | + | + | + | + | + | + | + | + | + | + | ||
| Head circumference (SD) | −2 | −1 | −2 | −2 | −1.5 | −1.5 | −1.5 | −2 | −1.5 | −2 | Mean | −2 | −1.5 | −1 | ||
| Flat occiput | + | + | + | + | + | + | + | + | + | − | − | − | − | − | ||
| Macrostomia | − | − | + | + | − | − | − | − | − | + | + | − | − | + | ||
| Tongue thrusting | − | + | + | − | − | − | − | − | − | + | + | + | − | + | ||
| Widely spaced teeth | − | + | + | + | − | − | − | − | − | + | + | + | + | + | ||
| Mandibular prognathism | − | − | + | − | + | + | − | − | − | + | + | − | − | + | ||
| Strabismus | − | − | + | + | + | − | − | − | − | − | + | − | − | − | ||
| Facial asymmetry | − | − | + | − | + | − | − | − | − | − | − | − | − | |||
| Scoliosis | − | − | − | − | + | ? | − | − | − | − | + | − | − | − | ||
| Height at last review (SD) | +1 | −1 | Mean | +1 | +1 | −2 | Mean | Mean | +1 | −2 | Mean | Mean | Mean | Mean | ||
| Overweight (⩾+1 SD) | +2 | − | +2 | +2 | +3 | +2 | +2 | +2 | − | +2 | +1 | +2 | +1 | +1 | ||
| Food attraction | + | + | + | + | + | + | + | + | + | + | + | + | + | + | ||
The difference in severity of ataxia is indicated by ++ typical, + mild, +/− extremely mild ataxia. Growth parameters (height, weight, head circumference) are described in standard deviations (SD). VA = valproic acid. BZP = benzodiazepine. Characteristic EEG patterns are defined by Boyd et al.19