Table 1.
Clinical features of affected individuals with RTN2-related distal hereditary motor neuropathy
| F1 | F2 | F3 | F4 | F5 | F6 | F7 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6a | Case 7 | Case 8 | Case 9 | Case 10 | Case 11 | Case 12 | Case 13 | Case 14 | |
| Ethnic origin | Iranian | Iranian | Indian | Tunisian | Indian | Egyptian | Pakistani | |||||||
| Age of onset | 2 | 2 | 1 | 2 | 5 | – | 2 | 6 | 1–2 | 2 | 1–2 | 1–2 | 5 | ∼5 |
| Current age/sex/consanguinity | 27/F/Y | 17/M/Y | 23/M/Y | 18/M/Y | 28/M/Y | – | 11/F/Y | 13/F/Y | 35/M/Y | 45/F/Y | 11/M/Y | 9/M/Y | 16/F/Y | 50/F/Y |
| Presentation | Tiptoe walking | Tiptoe walking | Foot drop, falls, muscle wasting LL | – | Falls, gait disturbance | Gait disturbance, tiptoe walking | Tiptoe walking | Gait disturbance | Falls, foot drop | Tiptoe walking | ||||
| Ambulatory status | Walks independently | Walks independently | Walks independently | – | Walks independently | Walks independently | Walks independently | Walks independently | ||||||
| Muscle weakness | Distal LL > UL, foot drop, weak finger extensors | Distal LL > UL, foot drop, weak finger extensors | Distal LL = UL, foot drop | – | Distal LL > UL, foot drop | Distal LL = UL, foot, drop, weak finger extensors | Distal LL = UL Foot drop |
Distal LL > distal.UL > Proximal LL Weak finger extensors |
Distal LL > distal.UL > Proximal LL Weak finger extensors |
Distal LL > distal.UL > Proximal LL Foot drop Weak finger extensors |
Distal LL > distal.UL > Proximal LL Foot drop Weak finger extensors |
|||
| Muscle atrophy | Distal UL and LL | Distal UL and LL | Distal UL and LL | – | Distal UL and LL | Distal UL and LL | Distal UL and LL | Distal LL | ||||||
| Hyperreflexia | Y | Y | Y | – | Y | Y | Y | Y | ||||||
| Ankle DTRs | Absent | Absent | Absent | – | Present | Absent | Absent | Absent | ||||||
| LL spasticity | Y | Y | Y | – | Y | Y | Y | Y | ||||||
| Babinski sign | Y | Y | Y | – | Y | Y | Y | Y | ||||||
| Movement abnormalities | Action tremor UL | Action tremor UL | N | – | N | N | N | N | ||||||
| Gait | Spastic | Spastic | Spastic | – | Spastic | Spastic | Spastic | Spastic | ||||||
| Sensory deficit | N | N | N | – | N | N | N | N | ||||||
| Bladder dysfunction | N | N | N | – | N | N | N | Urgency | Urgency | |||||
| Motor delay | N | N | N | – | Delayed walking (20 months) | N | N | Delayed walking (2 years) | N | Motor delay | ||||
| Cognitive impairment | N | N | N | – | N | N | N | N | ||||||
| Skeletal system | Pes planus | Pes cavus, hammer toes | Pes planus | – | Pes planus, SBD | Pes planus, hyperlordosis, SBD | Pes planus, hammer toes | Pes planus, hammer toes | Pes cavus | |||||
| Respiratory system | N | N | N | – | N | Bronchial asthma | N | N | ||||||
| Bulbar involvement | N | N | N | – | N | N | N | N | N | |||||
| Visual system | N | N | Congenital cataract | – | N | N | N | N | ||||||
| Electrodiagnostic | Axonal motor neuropathy with acute denervation and chronic neurogenic changes | Axonal motor neuropathy with acute denervation and chronic neurogenic changes | Axonal motor-predominant neuropathy with chronic neurogenic changes | – | Normal at 8 years old | Normal at 7 years old | Axonal motor neuropathy | Axonal motor and sensory neuropathy with chronic neurogenic changes | Chronic axonal motor neuropathy | Axonal motor neuropathy with chronic neurogenic changes | Axonal motor neuropathy with chronic neurogenic changes | |||
| Muscle MRI | Fatty infiltration, muscle atrophy and oedema in calf muscle compartments | NA | NA | NA (Elevated CK) | NA | Normal | NA | |||||||
| Brain MRI | Normal | Normal | NA | Normal | NA | Normal | Mildly reduced volume of posterior periventricular white matter and CC splenium | NA | ||||||
| RTN2 variant | Homozygous c.287del, p.(Pro96HisfsTer20) | Homozygous c.701_702dup, p.(Leu235HisfsTer18) | Homozygous c.571C>T, p.(Arg191Ter) | Homozygous c.577C>T, p.(Arg193Ter) | Homozygous c.285del, p.(Glu95AspfsTer21) | Homozygous c.79G > T, p.(Gly27Ter) | Homozygous c.178dupC, p.(Arg60ProfsTer11) | |||||||
CC = corpus collosum; CK = creatine kinase; ENMG = electroneuromyography; F = female; LD = learning difficulties; LL = lower limb; M = male; N = no; NA = not available; SBD = shoulder blades detachment; UL = upper limb; Y = yes.
aNot reported details due to refused patient consent.