Table 1 Overview of key recommendations for the differential diagnosis of chorea (modified from: Cardoso et al. [14], Hermann and Walker [44], Nguyen et al. [73], Schneider and Bird [95]
From: Differential diagnosis of chorea (guidelines of the German Neurological Society)
Pattern of inheritance | Autosomal-dominant | Huntington's disease (most common inherited chorea, generally with positive Family history and typical clinic, molecular genetic testing can be carried out as a next step; but ~ 8% without positive family history [111] C9orf72 mutations Spinocerebellar ataxia type 3, 2, 1, 7, 8, 12, 17, 48 DRPLA (especially Japan) HDL2 (especially of African origin) Neuroferritinopathy (NBIA) NKX2-1 (benign course of the disease) |
Autosomal-recessive | Wilson’s disease Neuroacanthocytosis Syndroms, VPS13A- and XK-disease /McLeod (CK, blood smear, chorein western blot) PLAN, PKAN2, aceruloplasminemia (NBIA) Friedreich’s Ataxia Niemann-Pick type C disease AOA1, AOA2 (now SCAN2), AT (AFP elevantion, Albumin reduced) Bilateral striatal necrosis, glutaric aciduria and similiar diseases in childhood | |
X-linked | McLeod-Syndrome (CK, blood smear, Kx and Kell blood group phenotype) FXTAS Lesch-Nyhan-Syndrome RETT Syndrome Metabolic diseases in childhood | |
According to course | Acute | Stroke/ICB |
Subacute | Metabolic Paraneoplastic Drug side effects Malignancies Prion diseases | |
Chronic progressive | Neurodegenerative | |
Not progressive | Drug side effects Benign Chorea (NKX2-1) | |
Episodic | Paroxysmal dyskinesias (PED, SLC2A1, Dyt 18) | |
Presenting predominantly in childhood (a selection) | Benign hereditary chorea (including thyroid-transcription-factor-1-gene, TITF1/NKX2-1 mutations; L-Dopa or methylphenidate treatment potentially helpful [32, 106] Paroxysmal dyskinesias (PED, SLC2A1, Dyt 18) NBIA Lesch-Nyhan-Syndrome, X-linked [44] RETT-Syndrome, X-linked [44] Mitochondriopathies [44] Polynucleotide kinase phosphatase (PNKP) mutation (rather benign course, early onset, with microcephaly, epilepsy, developmental delay, ataxia with oculomotor apraxia (AOA type 4) and polyneuropathy [12] ELAC2 gene mutations, rare mitochondrial disease with cardiomyopathy, children with developmental delay, possibly acanthocytes [76] FOXG1-, GNAO1-, GPR88-, SLC2A1-, SQSTM1-, ATP8A2-oder SYT-1-mutation [5] Hereditary disorders of glycosylation (CDG; in children [71] SCN2A mutation (neonatal, early childhood epilepsy, developmental disorders, possibly autism and episodic ataxia [115] PDE10A mutations, MRI with bilateral striatal lesions [68] KCNQ2 mutations, associated with fever [27] ATP1A3 mutations, alternating hemiplegia of childhood (AHC), rapid-onset dystonia, parkinsonism, CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss [100] ATP1A2 mutations with regression, hemiplegia, epilepsy [11] SUCLA2 mutations, mitochondrial DNA, hypotonia, Dyston/Leigh-like syndrome, deafness, but also myopathy, ataxia [36] Glutaric aciduria; AR [44] Non-inherited: Sydenham chorea | |
Symmetry | Asymmetric in diseases with structural lesion or metabolic cause (also generalized possible) | Stroke/ICB Post-pump chorea (after heart surgery) Infantile cerebral palsy Vasculitis, Moyamoya, multiple sclerosis, autoimmune diseases Tumor/structural lesion Polycythaemia vera Non-ketotic hyperglycaemia Chorea minor, antiphospholipid antibodies, drug-induced [19] |
Signs on | Asymmetric | structural lesion |
Subcortical dementia/Frontal lobe syndrome | Neurodegenerative | |
Ataxia | SCA 1–3, 7, 8, 12, 17, 48, DRPLA, AOA Typ I/II and others | |
Loss of reflexes/CK | Neuroacanthocytosis syndroms | |
Seizures | Juvenile Huntington’s disease, neuroacanthocytosis Syndromes (VPS13A- and XK-disease/McLeod), kinesigenic dyskinesia | |
MRI findings | Iron deposits | NBIA (chorea especially: PKAN 2, neuroferritinopathies (FTL), aceruloplasminemia) |
Calcium depositis (formerly “M. Fahr”) | Primary Familial Brain Calcification (SLC20A2-,PDGFB, PDGFRB others), parathyroid hormone disorders, possibly mitochondriopathy | |
Leukenzephalopathy | RNF216 | |
Atrophy pattern | Caudate atrophy in HD, cerebellar atrophy in ataxia | |
Structural lesion | Ischemic or hemorrhagic infarcts; neoplasms | |
Recommen-ded laboratory tests | Especially in sporadic cases | Routine lab, including liver parameters, CK (neuroacanthocytosis, but also after a fall, possibly blood smear asking for acanthocytes), vitamin B12, methyl-maleonate, ferritin, AFP (increased in AT and AOA II), albumin (decreased in AOA I) antistreptolysin (AST), Anti-DNAse B, Ceruloplasmin, Copper in serum and 24-h urine collection, ANA, ENA, antidouble-strand DNA (dsDNA), ANCA, RF, anti-gliadin Ab, paraneoplastic or antineuronal antibodies: e.g.: Anti-HU, -Yo, -Ma, -CRMP-5/CV2, anti-NMDA-Rec-Ab, anti-GAD-, anti-Iglon5-, anti-LGl-1-, phospholipid-Ab, cardiolipin-Ab, TSH (basal), anti-thyroid peroxidase (MAK) Ab, TSH receptor auto Ab (TRAK), parathyroid hormone, erythropoietin and hematocrit (Polycythemia vera), Treponema pallidum screening test, borrelia IgG/IgM Ab, HIV, possibly pregnancy test |