Video 1
The first patient’s office examination demonstrates a prominent risor grin, drooling and marked dysarthria. Asymmetric dystonia of the left arm and hand led to flexion posturing of the elbow, prominent wrist and finger flexion, and ulnar deviation of her wrist. A rostrocaudal gradient of dystonia is evident, with preservation of walking.
Video 2
Patient number 2 is shown in three segments. segment 1. A home video demonstrates an oculogyric episode, with eyes elevated upward with intermittent lateral deviation, accompanied by head tilt to the left and jaw deviation to the right. She was uncomfortable but did not lose consciousness. This episode lasted almost 1 minute, after which she partially recovered and looked exhausted. About 20 seconds afterwards, she developed oculogyria with upward eye deviation again. Segment 2. The second home video segment shows her in a stroller. She developed dystonic posturing of her neck with tilting to the left and lateral rotation to the right, accompanied by dystonic posturing of her hands and jaw opening. She recovered before her mother transferred her to a cushion. Segment 3. This video segment shows her during her initial office evaluation, already treated with levodopa. Her speech was mildly soft and indistinct with no ocular motor abnormalities. Mild symmetric dystonic posturing of both hands with intermittent choreiform movements of her fingers was present. There was no parkinsonism or dysmetria. She walked well with good arm swing.
Table 1
Clinical Features of Our Patients with Intermediate Forms of Alternating Hemiplegia of Childhood and Rapid-onset Dystonia–Parkinsonism
| Clinical Feature | Patient 1 | Patient 2 |
|---|---|---|
| Developmental delay | + | + |
| Drooling | +1 | + |
| Paroxysmal alternating hemiplegia | + | |
| Paroxysmal oculogyria | +1 | |
| Hypotonia | + | |
| Recovery of the episode with sleep | + | |
| Asymmetric dystonia | +1 | |
| Mild bilateral hand dystonia | +1 | |
| Rostrocaudal gradient of dystonia | +1 | |
| Speech involvement | +1 | +1 (mild) |
| Stabilization of the symptoms over time | + |
Table 2
Phenotype–Genotype Correlations of ATP1A3-related Disorders
| RDP | I | AHC | I | CAPOS |
|---|---|---|---|---|
| I274T, E277K, 327Ldel, T370N, W382R, L417P, T613M, S684F, R756H, I758S, F780L, D810Y, D923N | D801N1, G867D, D923N, E951K1 | S137Y, S137F, Q140L, I274N, E277K, V322D, C333F, T335P, G358C, L371P, G755A, G755S, G755C, L757P, T771N, S772R, N773S, N773I, D801E, D801N, T804I, D805E, M806R, I810F, I810S, S811P, E815K, 2542+1G>A (splice site), 919Vdel, D923N, D923Y, C927Y, C927F, C927W, G947R (2839G>A and 2839G>C), A955D, D992Y, 1013Ydup | E818K | E818K |
AHC, Alternating Hemiplegia of Childhood; CAPOS, Cerebellar ataxia, Areflexia, Pes Cavus Optic Atrophy, and Sensorineural Hearing Loss; RDP, Rapid-onset Dystonia–Parkinsonism.
The table demonstrates genotypes reported in the literature that are related to each phenotype classified into typical RDP, typical AHC, typical CAPOS syndrome, shown in pink, green, and blue, respectively.5,6,21,26–29 Intermediate (I) forms between each phenotype are shown in grey. Amino acid code alterations are shown in order of the codons.