Table 2.
Some of the possible adjunctive clinical features which can guide molecular diagnosis
| Disease | Inheritance | Nervous system | Cardiovascular system | Eye | Biochemical and MRI features | Others |
|---|---|---|---|---|---|---|
| MERRF | Matrilineal | Myoclonus, seizures, hearing loss, myopathy, cognitive impairment, neuropathy | – | – | Lactic acidosis, increased CK | Multiple lipomatosis |
| MELAS | Matrilineal | Stroke-like seizures, cognitive involvement, hearing loss, neuropathy, migraine, myopathy | Hypertrophic cardiomyopathy, Wolff–Parkinson–White | Eyelid ptosis, ophthalmoparesis, pigmentary retinopathy | Lactic acidosis, cerebral and cerebellar atrophy, white matter lesions, calcifications | Diabetes mellitus, short stature |
| Leigh syndrome | Matrilineal/recessive | Psychomotor regression, hypotonia, seizures, myoclonus, neuropathy, pyramidal signs | – | Optic atrophy, pigmentary retinopathy | Lactic acidosis, symmetrical lesions in the basal ganglia or brain stem | Early onset |
| NARP | Matrilineal | Neuropathy | – | Pigmentary retinopathy | – | – |
| PEO/KSS | Sporadic | Hearing loss, myopathy | Conduction blocks | Eyelid ptosis, ophthalmoparesis, pigmentary retinopathy | – | Short stature |
| POLG1 | Recessive (rarely dominant) | Seizures, hearing loss, myopathy, neuropathy | – | Eyelid ptosis, ophthalmoparesis | Cerebral and cerebellar atrophy | – |
| IOSCA | Recessive | Neuropathy | – | Eyelid ptosis, ophthalmoparesis | Brainstem and cerebellar atrophy | Early onset |
| OPA1 | Dominant | Hearing loss, neuropathy | – | Optic atrophy, eyelid ptosis, ophthalmoparesis | – | – |
| Coenzyme Q10 deficiency | Recessive | Myopathy; pure ataxic forms are frequent | – | – | Low coenzyme Q10 levels in muscle, cerebellar atrophy | Treatable (coenzyme Q10) |
| Complicated HSPs | Recessive (rarely dominant) | Pyramidal signs, neuropathy | – | – | Thin corpus callosum | – |
| Friedreich ataxia | Recessive | Pyramidal signs, loss of vibration and proprioceptive sense, areflexia | Hypertrophic cardiomyopathy | – | Brainstem atrophy | Diabetes. Treatable (idebenone) |
| Vitamin E deficiency | Recessive | Pyramidal signs, loss of vibration and proprioceptive sense, areflexia | – | Pigmentary retinopathy | – | Treatable (vitamin E) |
| Abetalipoproteinaemia | Recessive | Pyramidal signs, loss of vibration and proprioceptive sense, areflexia | – | Pigmentary retinopathy | Hypocholesterolaemia, acanthocytosis | Malabsorption. Treatable (vitamins) |
| Refsum disease | Recessive | Neuropathy, hearing loss, anosmia | Cardiomyopathy or arrhythmias | Pigmentary retinopathy | Renal failure | Treatable (diet) |
| Tay–Sachs disease | Recessive | Areflexia, muscle atrophy, psychiatric involvement, pyramidal signs, seizures | – | – | Cerebellar atrophy | – |
| Cerebrotendinous xanthomatosis | Recessive | Pyramidal signs, neuropathy, pyramidal signs, seizures, dementia | – | Cataracts | Increased serum cholestanol, cerebral and cerebellar atrophy, white matter lesions | Diarrhoea. Treatable (chenodeoxycholic acid) |
| NP-C | Recessive | Psychomotor regression, hypotonia, seizures, psychiatric involvement | – | Vertical gaze palsy | – | Splenomegaly. Treatable (miglustat) |
| Ataxia telangiectasia | Recessive | – | – | Oculomotor apraxia | Increased serum α-fetoprotein | Telangiectasias, immunodeficiency |
| Ataxia with oculomotor apraxia | Recessive | Neuropathy, extrapyramidal signs, mild cognitive impairment | – | Oculomotor apraxia, nystagmus | Cerebellar vermian atrophy | Treatable? (coenzyme Q10) |
| ARSACS | Recessive | Pyramidal signs, neuropathy | – | – | Cerebellar vermian atrophy, hyperintensity of the lateral pons | – |
| ARCA1 | Recessive | Dysarthria | – | – | Cerebellar atrophy | – |
| SCA1 | Dominant | Dementia, pyramidal signs, neuropathy | – | Nystagmus, slow saccades | Cerebellar and brainstem atrophy | – |
| SCA2 | Dominant | Dementia, neuropathy, myoclonus | – | Slow saccades | Cerebellar and brainstem atrophy | – |
| SCA3 | Dominant | Parkinsonism, pyramidal signs, neuropathy | – | Nystagmus, diplopia, ophthalmoplegia, eyelid retraction | Cerebellar and brainstem atrophy | – |
| SCA6 | Dominant | – | – | Nystagmus | Cerebellar and brainstem atrophy | – |
| SCA7 | Dominant | Pyramidal signs | – | Retinal degeneration, ophthalmoplegia | Cerebellar and brainstem atrophy | Anticipation |
| SCA17 | Dominant | Dementia, psychosis, chorea, seizures | – | – | Cerebellar and brainstem atrophy | – |
| DRPLA | Dominant | Dementia, chorea, myoclonus, seizures | – | – | Cerebellar and brainstem atrophy | Anticipation |
| Episodic ataxia | Dominant | Episodes of vertigo and ataxia | – | – | – | – |
| FXTAS | X-linked | Tremor, parkinsonism, neuropathy, autonomic dysfunction, dementia | – | – | Hyperintensity in the middle cerebellar peduncles and corpus callosum splenium | – |
| XLSA/A | X-linked | – | – | – | Anaemia | – |
ARCA1 autosomal recessive cerebellar ataxia type 1, ARSACS autosomal recessive spastic ataxia of Charlevoix-Saguenay, DRPLA dentate-rubro-pallidoluysian atrophy, FXTAS fragile X-associated tremor/ataxia syndrome, HSP hereditary spastic paraparesis, IOSCA infantile onset spinocerebellar ataxia, KSS Kearns–Sayre syndrome, MELAS mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome, MERRF myoclonic epilepsy with ragged red fibres, NARP neuropathy, ataxia and pigmentary retinopathy syndrome, NP-C Niemann–Pick disease type C, OPA1 optic atrophy 1 gene-related disease, PEO progressive external ophthalmoplegia, POLG mitochondrial DNA polymerase gamma related disease (types 1–3, 6, 7, 17), SCA spinocerebellar ataxia (types 1–3, 6, 7, 17), XLSA/A X-linked sideroblastic anaemia and ataxia