Table 1.
Clinical features of patients with variants in SNUPN
| Family/patient | F1.II.1 | F1.II.2 | F2.II.1 | F2.II.2 | F2.II.3 |
|---|---|---|---|---|---|
| Origin | Romania | Romania | Macedonia | Macedonia | Macedonia |
| Gender | M | F | F | F | F |
| Variant (protein) | p.Ile309Ser | p.Ile309Ser | p.Ile309Ser | p.Ile309Ser | p.Ile309Ser |
| Zygosity | HOM | HOM | HOM | HOM | HOM |
| Frequency genomAD (v4) | 0.000005472 | 0.000005472 | 0.000005472 | 0.000005472 | 0.000005472 |
| Age at onset | 4 years | 9 years | 9 years | 1 year | 2 years |
| Age at last examination | 17 years | 20 years | 29 years | 25 years | 24 years |
| Symptoms at onset | Difficulty climbing stairs | Difficulty running | Elbow contracture and rigid spine | Difficulties in getting up from the floor and climbing stairs | Hand weakness, difficulties climbing stairs |
| Course | Progressive | Progressive | Progressive | Progressive | Progressive |
| Neurodevelopmental delay | No | No | No | No | No |
| Lower limb weakness | Yes, p > d | Yes, p > d | Yes, p > d | Yes | Yes, p > d |
| Upper limb weakness | Yes, p > d | Yes, p | Yes | Yes | Yes |
| Facial muscle involvement | No | No | No | No | No |
| Hyperlordosis | Yes | Yes | Yes | Yes | Yes |
| Contractures | Yes (generalized) | Yes (feet) | Yes (generalized) | Yes (generalized) | Yes (neck) |
| Hyperlaxity | No | No | No | No | Yes |
| Respiratory involvement | Restrictive ventilatory dysfunction | Restrictive ventilatory dysfunction | Restrictive ventilatory dysfunction | Restrictive ventilatory dysfunction | Restrictive ventilatory dysfunction |
| Cardiac involvement | Incomplete right bundle block | No | No | No | No |
| Walking aid | Wheelchair | No | Walker | Wheelchair | No |
| CK (IU/l) | 1900–5750 | 1500–2600 | 1800 | 2300 | 290–350 |
| Muscles affected in MRI | Glutei, vasti, sartorius, gracilis, semitendinosus | Gllutei medium, vasti, sartorius, gracilis | Infraspinosus, supraspinosus, deltoids, biceps, paravertebral, sartorius, gracilis, adductor magnus, vasti, peroneal, medial gastrocnemiaus | Severely affected with extensive fat infiltration, including arms, paravertebral, thighs and legs | Infraspinosus, paravertebral, glutei medius, peroneal, tibialis anterior, medial gastrocnemius, solei |
| Myotilin deposits | Yes | Yes | N/A | N/A | Yes |
| Electron microscopy | Z-disc disorganisation, | Z-disc disorganisation, | N/A | N/A | Z-disc disorganisation |
| EMG | Myopathic | N/A | N/A | N/A | N/A |
| Nerve conduction studies | Normal | Reduced amplitude probably related to muscle atrophy | Normal | N/A | N/A |
| Other | – | – | Alport syndrome | Alport syndrome | Alport syndrome, myalgia |
F = female; M = male; HOM = homozygous; p = proximal; d = distal.