Table 1
Characterization of the clinical and genetic features of the described cases. Demographic, genetic and phenotypical characterization, as well clinical and medication history of the described cases are reported in the table. OD: oculus dexter (right ye); OS: oculus sinister (left eye).
| AGE OF ONSET | AGE AT DIAGNOSIS | CURRENT AGE | NEU1 GENETIC MUTATION | PRESENTING SYMPTOMS | PROGRESSION | CURRENT TREATMENT | |
|---|---|---|---|---|---|---|---|
| CASE 1 | 7 years | 8 years | 19 years | c.727G>A (p.G243R) + c.544A>C (p.S182R) | – Poor vision – 20/400 OD and OS –“cherry red spot” at ophthalmological evaluation | –Vision loss Small fiber neuropathy Lower limb more than upper limbs action myoclonus since the age of 13 years, mild wide based gait –Depression and attempted suicide | Trihexyphenidyl à clonazepam, levetiracetam |
| CASE 2 | 8 years | 32 years | 40 years | homozygous c.629C>T, (p.P210L) | –Loss of vision – 20/400 both eyes –“cherry red spot” at ophthalmological evaluation | –At the age of 14 years he developed action myoclonus of the upper limbs Balance impairment and wide based gait –Vocal myoclonus and myoclonus of the lower cranial region | Valproic acid à levetiracetam, perampanel à clonazepam, zonisamide. Sodium oxybate was attempted |
| CASE 3 | School age | 12 years | 31 years | c.644T>C (p.L215P) + c.649G>A (p.V217M) | –Difficulties seeing the blackboard (20/30 OD, 20/40 OS) – “cherry red spot” at ophthalmological evaluation | –Worsening of vision and color misperception –Gait ataxia, slurred speech and postural, action and stimulus sensitive myoclonus of the upper limbs since the age of 20 years –Generalized tonic-clonic seizures | Clonazepam/levetiracetam Sodium oxybate was attempted |
Video 1
Neurological examination of case 1–3. Segment 1: examination of case 1 shows mild myoclonus in the upper limbs, especially at target and with action, and cerebellar signs such as overshooting; gait was wide based and it presented frequent brakes due to myoclonic jerks in the lower limbs especially upon turning. Segment 2: case 2 was evaluated before and 45 minutes after the administration of Sodium Oxybate 1 gr. The two recording are presented side-to-side to help appreciating the improvement after the administration of the medication. At baseline, patient presented frequent volleys of resting, postural and action myoclonus in the upper limbs, especially at target, which significant impact on finalized activities (such as pouring water from a cup). After the administration of Sodium Oxybate 1 gr, postural and action myoclonus improved, allowing faster and smoother execution of different tasks, such as pouring water. Segment 3: postural and action myoclonus are noticeable in the upper limbs, mostly noticeable at target and with different tasks (i.e. drawing spirals and pouring water). Stimulus sensitive myoclonus to pin was present. Enhanced startle to unexpected sounds when walking. Tandem gait was affected.
Video 2
Eye movement assessments. Narrated video demonstrating clinically visible eye movement abnormalities in all 3 patients.
Figure 1
Fundus photographs of the right (A) and left (B) eyes of Case 3 demonstrating bilateral cherry red spots.
Figure 2
Eye movement recording of Case 3. A) Saccadic hypometria (undershoots). B) Slow horizontal saccades in main sequence. C) Saccadic smooth pursuit (upper figure – horizontal, and lower figure – vertical).