TABLE 2.
Conditions that associate movement disorders with cardiac involvement but with infrequent combination of clinical manifestations of both * **
| Disorders listed according to the predominant movement disorder | |
|---|---|
| Ataxia | Dystonia |
| Dandy‐Walker syndrome [HD‐M, heart insufficiency] | GM1‐gangliosidosis, type III (DYT/PARK‐GLB1) [CVA] |
| Ataxia‐telangiectasia (ATX‐ATM) [CAD, CVA, HD‐M] | ATP1A3‐related syndromes (DYT‐ATP1A3) and CAPOS syndrome [electrocardiographic abnormalities] |
| Primary coenzyme Q10 deficiency (COQ2 and COQ4) [HC, arrhythmias] | Primary coenzyme Q10 deficiency type 5 (COQ9) [HC, arrhythmias] |
| CANVAS (RFC1) [CAD] | Glutaric aciduria or acidemia, type I (GCDH) [HD‐M, cardiomyopathy, cardiac arrest] |
| Autosomal recessive spinocerebellar ataxia type 8 (ATX‐SYNE1) [HC, arrhythmias] Autosomal recessive spinocerebellar ataxia type 23 (TDP2) [arrhythmias] | 3‐methylglutaconic aciduria, type VIII (HTRA2) [arrhythmias] |
| Spinocerebellar ataxias (ATX‐ATXN1, ATX‐ATXN2, ATX‐ATXN3) [CAD], (ATX‐ATXN7), [HD‐M, CHF, cardiomyopathy, pericardial effusion], (ATX‐ATXN10) [HD‐M], (ATX‐PRKCG) [cardiomyopathy] | Early infantile epileptic encephalopathy type 75 (PARS2) [HC, DC] |
| Cockayne syndrome (ERCC4, ERCC5, ERCC6, ERCC8) [DC, arrhythmias, HD‐M] | 3‐methylglutaconic aciduria with deafness, encephalopathy, and Leigh‐like syndrome (SERAC1) [HD‐M, HC, arrhythmias] |
| Thiamine metabolism dysfunction syndrome‐5 or episodic encephalopathy attributed to thiamine pyrophosphokinase deficiency (TPK1) [HC] | 17‐beta‐hydroxysteroid dehydrogenase X deficiency or HSD10 mitochondrial disease (HSD17B10) [HC, DC, CCD] |
| Sandhoff disease (ATX/HSP‐HEXB) [CVA, HC, DC] | Severe dystonia, cerebellar atrophy, and cardiomyopathy likely caused by a missense mutation in TOR1AIP1 (TOR1AIP1) [DC] |
| Galactosialidosis (CTSA) [CVA] | Baraitser‐Winter syndrome (ACTB) [HD‐M] |
| Transthyretin‐related hereditary amyloidosis (TTR) [cardiac amyloid deposition, CCD, HC, CAD, heart failure] | Rett syndrome (MECP2) [CAD, arrhythmias] |
| Achalasia‐addisonianism‐alacrimia syndrome (AAAS) [CAD] | Chorea |
| Congenital disorder of glycosylation, type IIf (SLC35A1) [aortic insufficiency] | ADCY5‐related movement disorders (ADCY5) [DC, congestive heart failure] |
| Bardet‐Biedl syndrome (BBS1) [HC, HD‐M] | Paraneoplastic movement disorders [cardiac papillary fibroelastoma or mixoma] |
| Wolfram syndrome (WFS1) [HD‐M] | Polycythaemia vera or attributed to secondary causes [CVA, HD‐M] |
| Dihydrolipoamide dehydrogenase deficiency or Maple syrup urine disease type II (DLD) [HC] | Systemic Lupus erythematosus or antiphospholipid syndrome [CVA, coronary disease, cardiomyopathy] |
| Combined oxidative phosphorylation deficiency (TSFM, AIFM1, MTO1, and MTFMT) [HC, DC, HD‐M, CCD] | Myoclonus |
| Mitochondrial DNA depletion syndrome type 13; encephalomyopathic type (FBXL4) [HC, arrhythmias, CCD, HD‐M] | Myoclonic epilepsy of Lafora (MYC/ATX‐EPM2A and MYC/ATX‐NHLRC1) [CCD, heart failure, sudden death] |
| Thiamine‐responsive megaloblastic anemia syndrome (SLC19A2) [HD‐M, arrhythmias, HC, DC] | Action myoclonus‐renal failure syndrome (SCARB2) [DC] |
| Sideroblastic anemia with B‐cell immunodeficiency, periodic fevers, and developmental delay (TRNT1) [DC, heart failure] | Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (CACNA1B) [arrhythmias] |
| Peroxisome biogenesis disorder 9B (ATX‐PEX7) [cardiomyopathy, arrhythmias, heart failure] | TBC1D24‐related disorders—DOORS syndrome—and familial infantile myoclonic epilepsy (TBC1D24) [arrhythmias, cardiac arrest, HD‐M] |
| Short stature, microcephaly, and endocrine dysfunction syndrome (XRCC4) [DC] | PURA‐related neurodevelopmental disorders (PURA) [HD‐M] |
| Recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (TANGO2) [HC, DC, arrhythmias] | Microcephaly‐capillary malformation syndrome (STAMBP) [HD‐M, HC] |
| Mental retardation and distinctive facial features with or without cardiac defects (MED13L) [HD‐M] | Silver‐Russell syndrome, chromosome 11p15.5; dystonia is also a main movement disorder in this condition [HD‐M, DC, arrhythmias] |
| Harel‐Yoon syndrome (ATAD3A) [HC] | Combined oxidative phosphorylation deficiency type 35 (TRIT1) [HD‐M] |
| Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions (TWNK) [HC, CCD, arrhythmias] | Parkinsonism |
| Tics | Multiple system atrophy [CAD, sudden death] |
| Tourette syndrome [coronary disease, arrhythmias, CVA] | Progressive supranuclear palsy [CAD] |
| Tremor | Gaucher disease (GBA) [HD‐M, CVA, HC, DC, CAD, arrhythmias, cardiac amyloidosis] |
| Fragile X‐associated tremor/ataxia syndrome (FXTAS, ATX‐FMR1) [CVA, arrhythmias] | Fabry disease (GLA) [HC, CCD, arrhythmias, coronary disease, CVA, sudden death] |
| Mental retardation type 34 (NONO) [HD‐M, HC, DC] | Fahr's syndrome or idiopathic basal ganglia calcification (SLC20A2) [heart failure, arrhythmias, cardiomyopathy, CCD] |
| Multiple congenital anomalies, hypotonia, and seizures syndrome type 1 (PIGN) [HD‐M] | |
| Tonne‐Kalscheuer syndrome (RLIM) [HD‐M] | |
| Chromosome 18q deletion syndrome [HD‐M, CVA, congestive heart failure] | |
*
Clinical characteristics are shown in Table S1.
**
Gene symbols are in parentheses.
HD‐M, heart defects or malformations; CAD, cardiovascular autonomic dysfunction; CVA, cardiac valve abnormalities; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss; CANVAS, cerebellar ataxia, neuropathy, and vestibular areflexia syndrome; HC, hypertrophic cardiomyopathy; DC, dilated cardiomyopathy; CHF, congestive heart failure; CCD, cardiac conduction defects.