Clinical Characteristics of Alternating Hemiplegia of Childhood (AHC), Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss (CAPOS) Syndrome, and Rapid-onset Dystonia-Parkinsonism (RDP).
Clinical Characteristics of Alternating Hemiplegia of Childhood (AHC), Cerebellar Ataxia, Areflexia, Pes Cavus, Optic Atrophy, and Sensorineural Hearing Loss (CAPOS) Syndrome, and Rapid-onset Dystonia-Parkinsonism (RDP).
| Clinical Characteristic | AHC | CAPOS Syndrome | RDP |
|---|---|---|---|
| Age of onset | Before 18 months | Infancy–childhood (between 1 and 5 years of age) | After 18 months (often second to third decade) |
| Triggers | Excitement, extreme heat or cold, fever, food, lighting changes, physical exertion, stress, water exposure | Fever | Fever, running, alcohol binges, mild traumatic brain injury, overheating, emotional stress, infections, sleep deprivations, and childbirth |
| Onset | Acute | Acute–subacute ataxia | Abrupt onset over a few minutes to 30 days |
| Distribution | Hemiplegia/quadriplegia, rostrocaudal gradient, bulbar symptoms | Symmetric, ascending with or without bulbar symptoms | Asymmetric, rostrocaudal gradient, bulbar symptoms |
| Motor features | Dystonia, choreoathetosis | Ataxia | Dystonia, parkinsonism |
| Ocular involvement | Paroxysmal abnormal eye movement | Paroxysmal ophthalmoplegia | Paroxysmal abnormal eye movement |
| Peripheral nervous system | No | Areflexia, optic atrophy, sensorineural hearing loss | No |
| Pes cavus | No | Yes | No |
| Seizures | Yes | Inconsistent | Inconsistent |
| Other manifestations | Cognitive impairment, autonomic phenomena | None | None |
| Early symptoms | Paroxysmal ocular manifestations, seizures, developmental delay | Fever-induced transient encephalopathy | Vague symptoms of dystonia in distal limbs |
| Course | Polyphasic (relapsing-remitting) | Relapsing course of ataxia-encephalopathy (one to three episodes) with slow progression of other features | Rarely “secondary” exacerbations (2–3 episodes occurring 1–9 years after the initial onset) |
| Atypical manifestation | Benign familial nocturnal AHC; mild AHC; dystonia-predominant AHC; familial dominant pedigree; late-onset AHC; AHC without quadriparesis | Urinary urgency; cardiac arrhythmia; left ventricular arrhythmia; scoliosis; cognitive dysfunction; autistic traits; bradykinesia; myoclonus; chorea; tremor; oral dyskinesias; dystonia | Prominent lower limb dystonia; late onset (>50 years of age); gradual onset; pure dystonia; writer’s cramp; pyramidal signs; myoclonus; ataxia; chorea; hyporeflexia |
| Genotype-phenotype | 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 | I274T, E277K, 327Ldel, T370N, W382R, L417P, T613M, S684F, R756H, I758S, F780L, D810Y, D923N |