| Channelopathies | Sodium channel gene mutation | SCN1A gene mutation: severe myoclonic epilepsy of infants (Dravet syndrome), infants with febrile seizures presenting around 6 months of age with hemiclonic seizures18 |
| SCN2A gene mutation: benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy, late-onset episodic ataxia, myoclonus19 |
| SCN8A gene mutation: infant seizures not triggered by fever, multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures and epileptic spasms; seizures refractory to antiepileptic therapy, motor manifestations: hypotonia, dystonia, hyperreflexia, and ataxia86 |
| Potassium channel gene mutation | KCTD7 gene mutation: progressive myoclonus epilepsy, infant seizures, myoclonus, ataxia17 |
| KCNJ10 gene mutation: epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome), tonic-clonic seizures in infancy, later cerebellar ataxia, and hearing loss16 |
| Sodium/hydrogen channel gene mutation | SLC9A6 gene mutation: mental retardation, microcephaly, epilepsy, ataxia, Angelman-like syndrome87 |
| Calcium channel gene mutation | CACNA1A gene mutation: loss-of-function mutations classically present as episodic ataxia type 2 or progressive spinocerebellar ataxia (SCA6), minority of patients carrying CACNA1A mutations develop epilepsy, cognitive impairment, autism, and epileptic encephalopathy with mild cerebellar symptoms88 |
| Deficiency disorders and metabolically conditioned diseases | Mutation of FOLR1 gene (folic acid transport disorder) | Case study: ataxic syndrome in the second year of life, later a febrile tonic-clonic status, daily tonic and myoclonic seizures.28 |
| Autosomal recessive ataxia with vitamin E deficiency | Case study, caused by mutations of the α-tocopherol transport protein gene located on chromosome 8q1329 |
| GLUT-1 deficiency syndrome | Persistently low glucose in the cerebrospinal fluid, intellectual disability, epilepsy, movement disorders onset from infancy to adulthood: spasticity, ataxia, dystonia, caused by SLC2A1 gene mutation30 |
| Inherited glycosylation disorders | Systemic symptoms during infancy – susceptibility to infection, episodes of hepatic impairment, hemocoagulation impairment, childhood seizures and stroke-like episodes and later progressive limb atrophy with severe ataxia and intellectual deficiency, this group represents nearly 70 genetic disorders known to be caused by impaired synthesis of glycoconjugates89 |
| Wernicke’s encephalopathy | B1 deficiency, ataxia, ophthalmoplegia and confusion, additional symptoms: seizures, peripheral neuropathy, impaired vision and hearing to varying degrees90 |
| Lysosomal storage disease | Niemann-Pick C | NPC1 gene mutations, deficiency of sphingomyelinase, onset from infancy to adulthood, supranuclear gaze palsy followed by epilepsy development and later progressive gait ataxia91 |
| Lafora disease | Lafora bodies within the cytoplasm of cells, progressive myoclonus epilepsy, intractable tonic-clonic seizures, myoclonus, ataxia, visual hallucinations, and progressive dementia, onset in 2nd decade, fatal within 10 years92 Caused by mutations in either the EPM2A or EPM2B/NHLRC1 gene.93 |
| Neuronal ceroid lipofuscinoses | Accumulation of autofluorescent lipopigments resembling ceroid and lipofuscin, seizures, dementia, motor function impairment (myoclonus, ataxia, spasticity), vision loss, forms: infantile, late-infantile, juvenile, adult, most common infantile form (from 2 to 4 years of age), starting with epilepsy, later ataxia24 There are more than a dozen genes containing over 430 mutations underlying human NCLs have been identified, CLN1-14.94 |
| Sialoidoses | Neuraminidase deficiency caused by a mutation in the neuraminidase gene (NEU), located on 6p21.33, cerebellar ataxia, myoclonic epilepsy, myoclonus, macular cherry-red spots, onset from childhood to young adulthood95 |
| Gaucher disease | GBA gene mutation, hereditary glucocerebrosidase deficiency, type I (non-neuropathic) – hepatosplenomegaly, type II (acute infantile neuropathic) – hepatosplenomegaly and neurological symptoms: eye movement disorders, spasticity, seizures, limb rigidity, typically begins within 6 months of birth, type III (chronic neuropathic) – onset in childhood or even in adulthood, similar to type II but milder symptoms96 |
| Progressive myoclonus epilepsies | Leigh syndrome | Different inheritance patterns, genes contained in nuclear DNA or genes contained in mitochondrial DNA, mitochondrial syndrome, optic atrophy, ataxia, and dystonia, later epilepsy27 |
| MERRF | Mutation in the MT-TK gene of mitochondrial DNA, progressive course with worsening of the epilepsy and onset of additional symptoms including ataxia, deafness, muscle weakness (myopathy), and dementia97 |
| Unverricht-Lundborg disease | CSTB gene mutation, progressive myoclonus epilepsy, ataxia is an additional symptom98 |
| Action myoclonus-renal failure syndrome | SCARB2 gene mutation,99 progressive myoclonus epilepsy associated with renal dysfunction, severe progressive action myoclonus, dysarthria, ataxia, and later infrequent generalized seizures in 2nd or 3rd decade26 |
| May and White syndrome | Mitochondrial disorder, ataxia, severe action myoclonus, dysarthria, generalized seizures.100 |
| Immune-mediated conditions | Cerebellar ataxia and epilepsy with anti-GAD antibodies | Adult-onset cerebellar syndrome, ataxia and stiffness, incontinence, retinal pathologies, seizures, and immunological co-morbidities40 |
| Celiac disease | Neurological symptoms in up to 10% of cases, gastrointestinal symptoms preceding years of neurological symptoms, ataxia, myoclonus, tremor, seizures, abnormalities of eye movement31 |
| Hashimoto encephalopathy | Antibodies to thyroperoxidase, cerebellar ataxia occurs in more than half of patients, diffuse encephalopathy with cognitive abnormalities, tremor, myoclonus, seizures and sleep disturbances acute to subacute with a rapid progression onset in all age groups more common in females than in males90,101 |
| Hereditary ataxias | DRPLA | Highest frequency in the Japanese population, age of onset 1–60 years (mean age 28,8), early onset: myoclonus, epilepsy and mental retardation, late onset: cerebellar ataxia, choreoathetosis and dementia, caused by a mutation in the ATN1 gene – increased CAG trinucleotide repeat.102,103 |
| SCA2 | ATXN2 gene mutation, onset in the 3rd or 4th decade, truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea or parkinsonism104,105 |
| SCA10 | ATXN10 (E46L) gene mutation, onset from 18 to 45, slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances104,106,107,108 |
| SCA13 | KCNC3 gene mutation, onset in childhood, delayed motor and cognitive development followed by mild progression of cerebellar ataxia41,104,108 |
| SCA17 | TBP gene mutation, dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy42,104,107,109 |
| Friedreich ataxia | FXN gene mutation, ataxia followed by epilepsy, case report, ataxia, weakness and spasticity, sensory impairment, skeletal abnormalities, cardiac difficulties, diabetes43,110 |
| Ataxia teleangiectasia | ATM gene mutation, progressive cerebellar ataxia beginning between ages 1 and 4 years, oculomotor apraxia, choreoathetosis, telangiectasia of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma111 |
