Table.
Summary of the clinical, neurophysiological and biochemical features of the cases
| Previous study | Current study | |||||
|---|---|---|---|---|---|---|
| Family/patient/age at exam/sex | 1/1/37/M | 1/2/23/F | 2/1/26/M | 2/2/25/F | 3/1/14/M | 4/1/14/F |
| Ethnic origin | British | British | Indian | Indian | Greek Pomak | Pakistani |
| Consanguinity | Yes | Yes | Yes | Yes | No | Yes |
| Age of onset | Infancy | Infancy | Infancy | Infancy | Infancy | Infancy |
| CMS-associated features | ||||||
| Ocular involvement | Mild bilateral ptosis, no ophthal | Diplopia, no ptosis | Mild ophthal and ptosis | Mild ophthal and ptosis | Marked ptosis, mild ophthal | Mild ptosis, diplopia |
| Bulbar involvement | Yes | No | No | No | Yes | Yes |
| Weakness distribution | Proximal, UL = LL | Proximal, UL = LL, NF weakness | Proximal, UL = LL | Proximal, UL = LL | Proximal, UL = LL | Proximal, LL > UL, NF weakness |
| Fatigability | Yes | Yes | Yes | Yes | Yes | Yes |
| Treatment; response | AChEI—no response; 3,4-DAP—good response | AChEI—some response | AChEI and salbutamol—no response | AChEI and salbutamol—no response | AChEI—some response | AChEI—no response |
| Additional clinical features | ||||||
| Intellectual disability | Mild, attended mainstream school | Yes, attended school with additional support needs | Unable to read/write/calculate Binet-Kamat IQ score: 45 | Unable to read/write | Yes, attended school with additional support needs | Mild, attended mainstream school |
| Dysmorphism | No | No | Elongated facies, prominent ears, high arched palate | Elongated facies, prominent ears | No | No |
| Other | Pes cavus | Bicuspid AV and MV prolapse | Hypermobility, increase in lactate with exercise | Hyperextensible joints, chin fasciculations | Pes planovalgus | Weakness exacerbated by heat and cold. Marked increase in lactate with exercise |
| Neurophysiology | ||||||
| Repetitive nerve stimulation | No dec on 3 Hz stimulation, no inc after 20 s MVC | Not done | Decrement on 3 Hz stimulation (MVC not performed) | Decrement on 3 Hz stimulation (MVC not performed) | No dec on 3 Hz stimulation, no inc after 20 s MVC | No dec on 3 Hz stimulation (MVC not performed) |
| Single fibre EMG | Increased jitter and block | Not done | Not done | Not done | Not done | Jitter within normal limits |
| Additional analysis | ||||||
| Muscle biopsy | Normal COX staining, enlarged mitochondria and increased in number on EM | Not done | Not done | Not done | Fibre size variation, few central cores; sporadically accumulated mitochondria in EM | Mildly atrophic fibres, normal COX staining, mild reduction in complex 1 activity |
| Urine 2-hydroxyglutarate | Normal | Normal | Not done | Not done | Normal | Not done |
| MRI brain | Normal | Normal | Not performed | Normal | Not performed | Normal |
3,4-DAP 3,4-diaminopyridine, AChEI acetylcholinesterase inhibitor, COX cytochrome c oxidase, Dec decrement of compound muscle action potential, EM electron microscopy, EMG electromyography, Inc increment of compound muscle action potential, LL lower limb, MVC maximum voluntary contraction, NF neck flexor weakness, Ophthal ophthalmoplegia, RNS repetitive nerve stimulation, UL lower limb