TABLE 2.
Clinical Features of the Patients with Clinically Significant Pathogenic Mitochondrial DNA Variants in the 11,424 Exomes Analyzed
| Subject | Age, yr/sex | Subject phenotype | Muscle pathology and RCEA | Brain MRI | Family history |
|---|---|---|---|---|---|
| 1 | 3/M | Encephalopathy, lower limb spasticity, generalized tonic–clonic seizures, palatal myoclonus | NA | NA | NA |
| 2 |
82/M Deceased |
Progressive ataxia (onset in 50s), cognitive impairment | NA | Mild supratentorial atrophy with disproportionate cerebellar atrophy and sparing of the brainstem | Identical twin brother with ataxia |
| 3 | 13/M | Developmental delay, spastic‐dystonic gait, ID, axonal neuropathy | NA | NA | One older sibling with developmental delay and ID |
| 4 |
45/M Deceased |
Young adult onset progressive cerebellar ataxia, tremor, optic atrophy, neuropathy, myoclonic epilepsy, urinary frequency, atrial fibrillation | RRF | Basal ganglia changes and cerebellar atrophy | One affected brother (subject 5), mother asymptomatic (47% mutant load in blood), maternal grandmother with epilepsy |
| 5 | 49/M | Young adult onset progressive cerebellar ataxia, pyramidal signs, neuropathy, restless leg syndrome, ADHD | NA | Marked cerebellar atrophy | Less severely affected brother of subject 4 |
| 6 | 29/F | Stroke‐like episodes, cerebellar ataxia, left sided spastic hemiparesis, learning difficulties, seizures, optic atrophy, mild scoliosis, incomplete RBBB |
Mild increase in lipid, no RRF or COX negative fibers Low complex I |
White matter changes and high signal in right basal ganglia and right frontoparietal deep white matter | Mother asymptomatic |
| 7 | 27/M | Encephalopathic episode with bilateral INO and diplopia, nocturnal hypoventilation, reduced visual acuity, LVH |
Normal pathology Normal RCEA |
Symmetrical midbrain, pontine tegmental, brainstem and peduncular T2 signal hyperintensities | Mother and 2 brothers asymptomatic |
| 8 | 26/F | LS, learning disability, limb dystonia, regression of mobility and speech after the age of 9 yr, raised CSF lactate | NA | Basal ganglia lesions | Mother asymptomatic |
| 9 |
20/F Deceased |
Focal epilepsy, mild ID, failure to thrive, dysphagia, constipation, respiratory insufficiency with tracheostomy |
RRF Normal RCEA |
Bilateral and symmetrical T2 high signal in basal ganglia, white matter changes in the periventricular frontal region | NA |
| 10 | 52/F | Cognitive abnormalities, slowly progressive gait changes with onset at 30 yr | NA | NA | One affected brother (subject 11) |
| 11 |
45/M Deceased |
Gait changes with onset at 20 yr | NA | NA | One affected sister (subject 10) |
ADHD = attention deficit hyperactivity disorder; COX = cytochrome c oxidase; CSF = cerebrospinal fluid; ID = intellectual disability; INO = intra‐nuclear ophthalmoplegia; LS = Leigh syndrome; LVH = left ventricular hypertrophy; MRI = magnetic resonance imaging; NA = not available; RBBB = right bundle branch block; RCEA = respiratory chain enzyme activity; RRF = ragged red fibers.