Table 4.
Examples of defects in nuclear genes with a predominant muscular involvement phenotype.
| Genes | Type of Article | Patients/Age at Onset | Muscle Manifestations | Other Clinical Features | References |
|---|---|---|---|---|---|
| SUCLG1 | CR | 1 pt 6mo |
Marked muscular hypotonia, severe muscle atrophy | Failure to thrive | [134] |
| SUCLG1 | CR | 1 pt 17 h |
Axial hypotonia, no head control, poor swallowing and muscle weakness | Severe metabolic acidosis, liver failure | [132] |
| SUCLA2 | CS | 50 pts Median age: 2 mo |
Eyelid ptosis, ophthalmoplegia | Psychomotor retardation and failure to thrive, dystonia, hearing impairment, epilepsy | [132] |
| TK2 | CS | 92 pts Age range: birth–72 yo |
Proximal muscle weakness, high CK, ptosis, PEO, dysphagia, dysarthria/dysphonia, | seizures, encephalopathy and cognitive impairment, sensorineural hearing loss | [135] |
| DGUOK | CS | 6 pts Age range: 20 yo–69 yo |
PEO, ptosis, limb girdle weakness, myalgia, dysphonia, dysphagia | [129] | |
| DGUOK | CR | 1 pt 14 yo |
Fatigue during exercise | Abdominal pain, reduced left ventricular systolic | [136] |
| TYMP | CS | 102 pts Age range: 11–59 yo |
Bilateral ptosis, ophthalmoparesis, lower limb hyposthenia | Vomiting, abdominal pain, severe malnutrition | [14] |
| RRM2B | CS | 3 pts Age range: 8 we–27 mo |
Muscle hypotonia and progressive weakness, poor head control and respiratory distress. High CK | Failure to thrive and diarrhea, persistent acidosis, sensorineural hearing loss, retinopathy | [137] |
| RRM2B | CS | 31 pts Age range: 0–6 mo |
Muscular hypotonia, respiratorydistress | Failure to thrive, hearing loss, encephalopathy, seizures. Renal, eye and GI involvement. Anemia | [138] |
| POLG | CS | 95 pts Age range: 2–23 yo |
Myopathy, ptosis and PEO, neck flexor weakness | Seizures, hepatopathy, lactic acidaemia, sensory ataxia, bradykinesia | [123] |
| Twinkle | CS | 4 pts Age range: 20s–30s |
Ptosis and ophthalmoplegia, diplopia | Gait difficulty, stiffness, resting tremor, depression | [127] |
| SLC25A4 | CS | 25 pts Age range: 0–48 yo |
Myopathy and muscle hypotonia, dysarthria, respiratory insufficiency | Ischemic stroke, hydrocephalus, insomnia, mental retardation, headache, cardiomyopathy, cataracts, scoliosis | [121] |
| MGME1 | CS | 6 pts Age range: NA |
PEO, proximal weakness, generalized muscle wasting, respiratory failure, exercise intolerance | Mental retardation, depressive episodes, gastrointestinal symptoms, spinal deformities, ataxia, dilated cardiomyopathy and arrhythmias, | [128] |
| OPA 1 | CS | 8 pts Age range: birth–60 yo |
Ptosis and ophthalmoplegia, exercise intolerance and myalgia, muscle weakness | Optic atrophy, hearing loss, pes cavus, feeding difficulties | [139] |
| SPG7 | CS | 9 pts Age range: Late20s–Mid60s |
Ptosis and ophthalmoplegia, proximal myopathy, dysphagia, dysphonia, dysarthria | Spasticity, ataxia, bladder symptoms, mild cognitive impairment | [140] |
F: female; M: male; NA: not available yo: years old; CR: case report; CS: cohort study.