Figure 1
Adult-onset choreas.
HD: Huntington disease; HDL: Huntington-disease like; SCA: spinocerebellar ataxia; DRPLA: dentatorubropallidoluysian atrophy; SLE: systemic lupus erythematosus; APS: antiphospholipid syndrome; NMDAR: n-methyl-d-aspartic acid receptor.
Adapted from: Hermann A, Walker RH. Diagnosis and treatment of chorea syndromes. Current neurology and neuroscience reports 2015;15:514.
Figure 2
Early/Childhood-onset choreas.
HDL: Huntington-disease like; AOA: ataxia with oculomotor apraxia; ASO: antistreptolysin O; SPG: spastic paraplegia.
Adapted from: Hermann A, Walker RH. Diagnosis and treatment of chorea syndromes. Current neurology and neuroscience reports 2015;15:514.
Table 1a
Characteristics of adult-onset autosomal dominant hereditary choreas.
| Disease; Gene | Region; Age | Mov Disord | Key Findings | Other Sx | NPsych | CI/Dem | I and L |
|---|---|---|---|---|---|---|---|
| Huntington’s disease; Huntingtin (HTT) | 20–40 yrs.* | Chorea Parkinsonism, dystonia, myoclonus if young onset | – | Hung-up knee jerk reflex | Yes | Yes | I: Striatal volume loss |
| C9orf72 expansions; C9orf72 | Caucasian; 40–50 yrs. | HD phenocopy | – | – | Yes | Yes | I: Generalized cerebral atrophy |
| Spinocerebellar ataxia 17; TATA box-binding protein (TBP) | Caucasian and Asian; 20–40 yrs. | HD phenocopy Dystonia, tremors, parkinsonism | Ataxia predominates | Pyramidal signs Seizures | Yes | Yes | I: caudate or cerebellar atrophy |
| Huntington disease-like 2; Junctophilin-3 (JPH3) | African ancestry; 40–50 yrs. | HD phenocopy | – | – | Yes | Yes | I: Similar to HD |
| Dentatorubropallidoluysian atrophy; Atrophin-1 (ATN1) | Japanese; 30 yrs. | HD phenocopy Myoclonus | – | Ataxia Seizures | Yes | Yes | I: White matter lesions and cerebellar/brainstem atrophy |
| Neuroferritinopathy; Light chain of ferritin (FTL) | Cumbrian region of northern England; 40 yrs. | HD phenocopy Dystonia, parkinsonism | Oromandibular chorea predominate | Spasticity Ataxia | Yes | Yes | I: Iron accumulation or cystic changes in basal ganglia or cortical regions with pallidal necrosis and edema in later stages L: Low serum ferritin levels |
| Familial prion disease (Huntington disease-like 1); Prion protein (PRNP) | 20–40 yrs. | HD phenocopy Myoclonus | Rapidly progressive | Seizures Ataxia | Yes | Yes | – |
| Spinocerebellar ataxias types 1, 2, 3, 7, 12, 48; ATXN 1, 2, 3, 7, 12, 48 | European, Cuban, Indian (SCA 2); 30 yrs.* | HD phenocopies Dystonia, myoclonus, parkinsonism | Ataxia | Pyramidal signs Oculomotor abnormalities Slow saccades (SCA2) Facio-lingualfasciculations (SCA2) | No | Yes | I: Pontine and cerebellar atrophy; T2 hyperintensities in dentate nuclei extending to middle cerebellar peduncle (SCA48) |
| Primary familial brain calcification; SLC20A2 | 30–40 yrs. | Akinetic syndrome, tremor, chorea, dystonia | – | – | Yes | Yes | I: Caudate, brainstem, thalami, cerebellum, white matter, cortical calcifications |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; NPsych: Neuropsychiatric features; CI/Dem: Cognitive impairment or dementia; I: Imaging; L: Laboratory; HD: Huntington’s disease.
* Inversely related to the size of the repeat expansion
Table 1b
Characteristics of adult-onset autosomal recessive hereditary choreas.
| Disease; Gene | Region; Age | Mov Disord | Key Findings | Other Sx | NPsych | Ci/Dem | I and L |
|---|---|---|---|---|---|---|---|
| Chorea-acanthocytosis; VPS13A | 20–40 yrs. | Generalized chorea, dystonia, tics, parkinsonism | Self-injurious orofacial dyskinesia Rubber-person-like gait | Sp & Sw and problems Feeding dystonia Hypersalivation Head drops Myopathy or neuropathy Seizures | Yes | Yes | I: Caudate atrophy L: Acanthocytes on blood smear, CPK and LFT elevation |
| Aceruloplasminemia; CP | 40–50 yrs. | Chorea Parkinsonism | Retinal degeneration | Ataxia | Yes | Yes | I: Symmetrical iron deposition in the basal ganglia, thalamus, red nuclei, and dentate nuclei L: Anemia, DM |
| Wilson’s disease; ATP7B | 6–50 yrs. | Dystonic/choreic syndrome Parkinsonian syndrome | Kayser-Fleischer rings | Ataxic syndrome | Yes | Yes | I: “Face of the giant panda” in midbrain L: Low serum ceruloplasmin levels, Elevated 24-hours copper excretion, Hemolytic anemia, Elevated LFTs |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; NPsych: Neuropsychiatric features; CI/Dem: Cognitive impairment or dementia; I: Imaging; L: Laboratory; Sp: Speech; Sw: Swallowing.
Table 1c
Characteristics of childhood-onset autosomal dominant hereditary choreas.
| Disease; Gene | Region; Age | Mov Disord | Key Findings | Other Sx | NPsych | CI/Dem | I and L |
|---|---|---|---|---|---|---|---|
| ADCY5 mutation; ADCY5 | 0–20 yrs. | Chorea, myoclonus, dystonia | Episodic exacerbations of dyskinesia upon awakening or when falling asleep | Delayed milestones and axial hypotonia | No | No | – |
| Benign Hereditary Chorea; NKX2-1 | 1–20 yrs. | Chorea with mild progression | Pulmonary and thyroid problems | Short stature Developmental delay | No | No | – |
| Tuberous sclerosis; TSC1 and TSC2 | 10 yrs. | Chorea | Benign tumors Skin abnormalities | Behavioral symptoms Seizures Developmental problems | Yes | Yes | I: Subependymal nodules and cortical/subcortical tubers |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; NPsych: Neuropsychiatric features; CI/Dem: Cognitive impairment or dementia; I: Imaging; L: Laboratory.
Table 1d
Characteristics of childhood-onset autosomal recessive hereditary choreas.
| Disease; Gene | Region; Age | Mov Disord | Key Findings | Other Sx | NPsych | CI/Dem | I and L |
|---|---|---|---|---|---|---|---|
| Friedreich’s ataxia; Frataxin | 10–15 yrs. | Chorea is rare | Ataxia Foot deformities Areflexia | Peripheral neuropathy Diabetes Cardiomyopathy Scoliosis | No | No | NCS: Abnormal sensory nerve action potentials I: Atrophy of cervical spinal cord with minimal cerebellar atrophy |
| Ataxia telangiectasia; ATM | 1–4 yrs. | Choreoathetosis | Prominent ataxia Telangiectasias | Peripheral neuropathy Oculomotor apraxia Predisposition to immunological disorders and cancer | No | No | I: cerebellar atrophy L: Serum alpha-fetoprotein is elevated and IgA, IgE, IgG2 deficiency |
| Ataxia with oculomotor apraxia types 1 and 2; APTX and SETX | 2–10 yrs. (AOA1) 3–30 yrs. (AOA2) | Chorea, dystonia | Oculomotor apraxia Ataxia | Axonal sensorimotor neuropathy | No | Yes | I: Cerebellar atrophy L: Hypoalbuminemia and Hypercholesterolemia (AOA1), Elevated serum alpha-fetoprotein (AOA2) |
| Xeroderma pigmentosum; XP | 1–2 yrs. | Chorea in advanced stages | Cutaneous photosensitivity Freckle-like pigmentation on face Conjunctival telangiectasia Optic atrophy Dry skin Predisposition to skin cancer | Ataxia Seizures Areflexia Peripheral neuropathy Sensorineural hearing loss Abnormalities in dentition | No | Yes | – |
| Huntington disease-like 3; unknown | Saudi Arabian; 3–4 yrs. | Chorea, dystonia | – | Ataxia Gait instability Spasticity Seizures Mutism | No | Yes | I: Frontal and caudate atrophy |
| Spastic ataxia type 2 (SPG58); KIF1C | 10–20 yrs. | Chorea Dystonia | Spastic gait Ataxia | Hyperreflexia and spasticity Developmental delay | No | Yes | I: Demyelination and cerebellar atrophy |
| PDE10A mutation; PDE10A | 5–15 yrs. | Chorea | Diurnal fluctuations | – | No | No | I: Symmetrical T2-hyperintense striatal lesions |
| GPR88 mutation; GPR88 | Palestinian; 8–9 yrs. | Chorea | – | Developmental delay | No | Yes | – |
| Hereditary Epileptic-Dyskinetic Encephalopathies; FOXG1, GNAO1, GRIN1, FRRS1L, IRF2BPL | Neonatal to 8 yrs. | Chorea, dystonia, ballism, stereotypies | Early-onset, drug-resistant seizures Facial and oro-lingual dyskinesias | Developmental delay Oculogyric crises, cortical blindness, spastic tetraparesis (GRIN1) | No | Yes | I: corpus callosum hypoplasia, delayed myelination, simplified gyration (FOXG1) |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; NPsych: Neuropsychiatric features; CI/Dem: Cognitive impairment or dementia; I: Imaging; L: Laboratory.
Table 1e
Characteristics X-linked hereditary choreas.
| Disease; Gene | Region; Age | Mov Disord | Key Findings | Other Sx | NPsych | CI/Dem | I and L |
|---|---|---|---|---|---|---|---|
| McLeod syndrome; XK | Before 40 yrs. | Chorea, dystonia, parkinsonism | Areflexia Sensorimotor axonopathy | Cardiomyopathy Arrhythmias MyopathySeizures | Yes | No | L: Elevated serum liver enzymes and creatine kinase I: caudate nucleus and putamen atrophy |
| Pelizaeus-Merzbacher disease; PLP1 | Neonatal to 5 yrs. | Choreoathetosis Dystonia | Pendular nystagmus Spasticity Head tremor Generalized hypotonia | Ataxia Mental retardation | No | Yes | I: Hypomyelination of corona radiata, optical radiations, internal capsule |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; NPsych: Neuropsychiatric features; CI/Dem: Cognitive impairment or dementia; I: Imaging; L: Laboratory
Table 2
Characteristics of inborn errors of metabolism and mitochondrial cytopathies where chorea is the predominant movement disorder.
| Type of Metabolic Disorder | Conditions; Gene | Region; Age | Inheritance Pattern | Mov Disord | Key Findings | Seizures | Ataxia | Pyramidal signs | DD | Other Sx | I and L | Tx |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Organic acidemias | Glutaric aciduria type 1; GCDH | Neonatal | AR | Choreo-athetosis Dystonia Orofacial dyskinesia | Macrocephaly Acute encephalopatic crisis Opisthotonus | Yes | No | No | Yes | No | L: urinary glutaric acid, 3-hydroxyglutaric acid, glutaconic acid. | Low lysine diet and oral carnitine supplementation |
| Propionic acidemia; PCCA and PCCB | Amish, Inuit of Greenland and Saudi Arabian populations; Neonatal or infancy | AR | Choreoathetosis | Poor feeding Lethargy Encephalopathy Vomiting Hypotonia | Yes | No | Yes | Yes | Hepatomegaly Failure to thrive Optic atrophy Hearing loss Premature ovarian failure Chronic renal failure Cardiomyopathy Attention-deficit disorder Autism | L: Plasma amino acids, acylcarnitines, and urinary organic acids, and orotic acid. I: Lesions in the bilateral lenticular and caudate nuclei | Protein-restricted diet; Treat metabolic acidosis, hypoglycemia, hyperammonemia | |
| Methylmalonic acidemia; MUT | First year | AR | Choreoathetosis Dystonia | Encephalopathy Stroke Hypotonia Lethargy Monilial infections | Yes | No | No | Yes | Dysphagia Dysarthria Failure to thrive Hepatosplenomegaly | L: Elevated blood and urine levels of ammonia, glycine, methylmalonic acid, propionic acid. I: Bilateral globus pallidus lesions | Protein-restricted diet, cyanocobalamin, and levo-carnitine supplementation | |
| OPA3-related 3-methylglutaconic aciduria (Costeff syndrome); OPA3 | Iraqi-Jewish descent; Before age ten years | AR | Choreoathetosis | Optic atrophy Spastic paraparesis | No | Yes | No | No | No | L: Urinary excretion of 3-methylglutaconic acid | Supportive | |
| Amino acid metabolism | Nonketotic hyperglycinemia; GLDC or AMT | Neonatal, infancy, adulthood | AR | Chorea | Lethargy, coma Hypotonia, hiccups Myoclonic jerks | Yes | No | Yes | Yes | Breathing/swallowing disorders | I: Elevated glycine levels in CSF and plasma. | Sodium benzoate Dextromethorphan Seizure management |
| Homocystinuria; CBS MTHFR, MTR, MTRR, MMADHC | 1st or 2nd decade | AR | Chorea Dystonia | Ectopia lentis, severe myopia Thromboembolism Skeletal and skin abnormalities | Yes | No | No | Yes | No | L: Increased serum levels of homocysteine and methionine | Vitamin B6 Methionine-restricted diet Folate Vitamin B12 Betaine | |
| Purine metabolism | Lesch-Nyhan disease; HPRT1 | 3 to 6 mo. | X-linked | Choreoathetosis Dystonia | Self-injurious behavior Gouty arthritis Crystals or calculi in kidneys, ureters, bladder | No | No | Yes | Yes | Hypotonia Behavioral disturbances | L: Urinary urine-to-creatine ratio greater than 2.0 Hyperuricemia Hyperuricuria | Allopurinol Symptomatic |
| Creatine metabolism | Cerebral creatine deficiency syndrome 2 (GAMT deficiency); GAMT | Early infancy to 3 yrs. | AR | Choreoathetosis Dystonia | Hyperactivity, autism, self-injurious behavior | Yes | Yes | No | No | No | I: Hyperintensities in basal ganglia | Creatine monohydrate supplementation Ornithine supplementation Protein- or arginine-restricted diet |
| Glucose transport | GLUT1 deficiency; SLC2A1 | Infancy | AD; AR | Chorea Dystonia | Paroxysmal episodes of mov disord or epilepsy Atypical childhood absence epilepsy Myoclonic astatic epilepsy | Yes | Yes | No | Yes | Microcephaly | L: Low CSF:serum glucose ratio | Ketogenic diet Symptomatic |
| Lipid storage | Niemann Pick Type C; NPC1 or NPC2 | Infancy, children, adults | AR | HD phenocopy in adult onset Dystonia | Vertical supranuclear gaze palsy Dementia | Yes | Yes | No | Yes | Hypotonia Liver disease Respiratory failure | I: cerebellar atrophy or periventricular hyperintensities | Symptomatic |
| Other | Sulfite oxidase deficiency; SUOX | Infancy | AR | Choreoathetosis Dystonia | Ectopia lentis Eczema Failure to thrive | Yes | Yes | No | Yes | Hypotonia | L: Increase sulfite levels in urine I: Calcification of basal ganglia and cerebellar hypoplasia | Low sulfur amino acid diet Low protein diet |
| Mitochondrial cytopathies | Leigh syndrome and Leigh-like syndromes; MT-ND, MTATP6 | First mo. to yrs. of life | X-linked, AR | Choreoathetosis Dystonia Parkinsonism | Ophthalmologic abnormalities Cardiac, hepatic, gastrointestinal and renal symptoms. | No | Yes | No | Yes | Hypotonia | L: Increased blood lactate levels. I: T2-weighted hyperintensities in basal ganglia and brainstem. | Biotin, thiamine, Coenzyme Q10 supplements |
| Pyruvate carboxylase deficiency; PC | First yr. | AR | Choreoathetosis Tremors | Microcephaly Disconjugate eye movements, poor pupillary response, blindness, poor visual tracking Respiratory abnormalities | Yes | Yes | Yes | Yes | Hypotonia | L: Elevated blood levels of ammonia, pyruvate, lactate, acetoacetate and beta-hydroxybutyrate. I: periventricular WM cysts, subcortical FP hypernintensities. | Cofactor supplementation with thiamine and lipoic acid and administration of dichloroacetate | |
| Pyruvate dehydrogenase complex deficiency; PDHA1 | Infancy | X-linked | Choreoathetosis Dystonia | Poor feeding Lethargy Tachypnea Abnormal eye movements Dysmorphic features Respiratory abnormalities | Yes | Yes | Yes | Yes | Microcephaly Hypotonia | L: Elevated blood levels of lactate and pyruvate I: absence of corpus callosum and medullary pyramids, ectopic inferior olives, symmetric cystic lesions and gliosis, generalized hypomyelination. | Cofactor supplementation with thiamine, carnitine, and lipoic acid. |
[i] Mov Dis: Movement Disorders; Sx: Symptoms; DD: Developmental delay; I: Imaging; L: Laboratory; AR: Autosomal recessive; AD: Autosomal dominant; CSF: cerebrospinal fluid; WM: white matter; FP: frontoparietal.
* Only the disorders of metabolism where chorea is the predominant movement disorder are included.
* Wilson’s disease is described under autosomal recessive hereditary choreas.
Table 3
Causes of acquired choreas.
| Etiology | Disease |
|---|---|
| Pharmacological | Acute drug-induced, Tardive chorea, Alcohol, Other toxins |
| Vascular | Stroke, Subdural or Extradural Hematomas, Small vessel disease |
| Hematological | Polycythemia vera, Essential thrombocythemia, Transitional myeloproliferative disease |
| Autoimmune | SLE, APS, NMDAR encephalitis, Behcet’s disease, Sjögren syndrome, Celiac disease, IgLON5, D2R, GABAaR, and Neurexin-3 alpha |
| Endocrine/Metabolic | Hyperthyroidism, Hypocalcemia, Hyper/Hyponatremia, Hyperglycemia, Hypomagnesemia, Uremia, Non-wilsonian hepatolenticular degeneration, Kernicterus |
| Nutritional | Vitamin B12 and B1 deficiency |
| Demyelinating disorders | Multiple Sclerosis, ADEM, Central pontine and extrapontine myelinolysis |
| Neoplastic | Primary or Secondary |
| Paraneoplastic | Anti-CRMP5, Anti-Hu, Anti-Ma, Anti-P/Q and N-type V-G calcium channel, Anti-NMDAR, Anti-LGI1, Anti-Caspr2 |
| Infectious/Parainfectious | Sydenham’s chorea, Bacterial, Viral, Spirochetal |
| Brain hypoxia | Cardiac arrest, Respiratory insufficiency, Anesthetic complication, Hypothermia, CO Poisoning, Post pump chorea |
| Other | Mastocytosis, Chorea gravidarum, Cerebral palsy |
[i] SLE: systemic lupus erythematosus; APS: anti-phospholipid syndrome; NMDAR: anti-n-methyl-d-aspartate receptor; ADEM: acute disseminated encephalomyelitis.