Table 1 Clinical, electroencephalogram (EEG), and radiological features of patients with truncating IRF2BPL variants
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
Gender | M | F | M | F | M | M | F | M | M | F | F |
Variation (cDNA) | c.519C>G | c.361C>T | c.376C>T | c.496G>T | c.519C>G | c.562C>T | c.962delC | c.2122delG | c.2135_2136delGT | NA | c.2152delT |
Variation (amino acid) | p.Tyr173* | p.Gln121* | p.Gln126* | p.Glu166* | p.Tyr173* | p.Arg188* | p.Ala321Glufs*24 | p.Ala708Profs*59 | p.Leu713Serfs*56 | p.Cys714Alafs*49 | p.Cys718Alafs*48 |
Mensurations at last examination (age) | 10 years 5 months | 27 years | 23 years | 48 years | 8 years | 20 years | 10 years 5 months | 3 years | 5 years | 3 years 7 months | 2 years 2 months |
Weight in kg (centile) | 19.7 (<<3rd) | NA | 70 (50th) | NA | 16.5 (<<3rd) | 66 (25–50th) | 20 (<<3rd) | 17.5 (95th) | 22 (90th) | 16.3 (75–90th) | NA |
Length in cm (centile) | 119 (<<3rd) | NA | 170 (10–25th) | NA | 110 (<<3rd) | 141 (<<3rd) | 110 (<<3rd) | 103 (95th) | 110 (50–75th) | 107.3 (97th) | NA |
OFC in cm (centile) | 49.5 (<3rd) | NA | 53.5 (10–25th) | NA | 51.2 (25th) | 59 (>97th) | 49 (<<3rd) | 50 (50th) | 52.5 (50–75th) | 49.5 (25–50th) | 47 (50th) |
Birth mensurations (WG) | 38 | NA | 36 | At term | 36 | NA | 40 | 38 | 31 | 40 | 38 |
Weight in g (centile) | 3210 (25th) | NA | 2650 (10th) | m | 3060 (25th) | 3600 (50th) | 3070 (25th) | 3470 (50th) | 1750 (75th) | 3864 (90th) | 3500 (50–75th) |
Length in cm (centile) | 50.5 (50–75th) | NA | 47 (10–25th) | NA | NA | NA | 50 (50–75th) | 51 (50–75th) | NA | 57.2 (>97th) | 55 (>97th) |
OFC in cm (centile) | 34 (25–50th) | NA | 33 (10th) | NA | NA | NA | 33 (10th) | 36 (50–75th) | NA | NA | NA |
Facial dysmorphism | + | - | + | - | + | - | + | - | + | + | + |
Developmental features | |||||||||||
Axial hypotonia | + | NA | + | NA | + | - | + | + | + | + | + |
Sitting age (months) | 9 | NA | 8 | Normal | 6 | Normal | No sit | 9 | NA | 11 | No sit |
Walking age (months) | 12 | 12 | 15 | 9 | 12 | Normal | No walk | 19 | 18 | 17 | No walk |
Speech delay | + | + | + | NA | + | - | + | - | + | + | + |
Loss walking age (years) | NA | 22 | Still walking | NA | 4 | 10 | Never walked | NA | NA | NA | Never walked |
Age at regression onset | 2.5 years | 5–6 years | 17 years | 10 years | 2.5 years | 7 years | First months | 3 year | 1 year | No regression | 6 months |
Neurological features | |||||||||||
Dystonia | + | - | + | NA | - | + | - | + | - | - | - |
Ataxia | + | - | + | + | + | + | + | + | - | - | - |
Other | Choreathetosis,vertical occulomotor paralysis, horizontal nystagmus, upper limb tremor | Pyramidal syndrome | Pyramidal syndrome, cerebellar dysarthria, slow dysmetric eye saccades | Cerebellar dysmetry | Pyramidal syndrome, nonverbal, visual tracks, intermittent smiles, dysphagia | Spastic tetraparesis, dysarthria, nystagmus, ophthalmoplegia, dysphagia, myoclonic jerk | Quadriplegic hypotonic–ataxic tetraparesis, intermittent nystagmus | Ankle spasticity, dysarthria, dysphagia | Autism | Dysphagia | Total spasticity |
Epilepsy details (age of onset, seizure types) | 8.5 years: seizures | 13 years: tonic–clonic | 7 months: spasm, myoclonus 17 years: myoclony | 26 years: seizures 35 years: myoclonus | No clinical seizure | No clinical seizure | 2.5 months: tonic–clonic | No clinical seizure | 5 years | No clinical seizure | 6 months: West syndrome |
EEG anomalies | Points and diffuse waves predominating | Multifocal polyspikes and waves | Spikes and waves | Spikes and polyspikes | Frequent intermittent polymorphic theta slowing | Normal | Multifocal cerebral hyperexcitability with intermittent delta waves and sharp slow waves, hypsarrhythmia | Normal | Frequent centrotemporoparietal spikes alternating left and right, aggravated by sleep | NA | At seizures onset, hypsarrhythmia; at 1 year, diffuse discharge in the left hemisphere; at 2.2 years, diffuse discharges |
Treatment | TP, CZ, Neurontin | Lamotrigine, LV, CBZ, VPA, clobazam | VGA, hydrocortisone, and VPA 17 years: VPA, lamotrigine | CZ, LV | Amantadine, L-dopamine, carbidopamine | Baclofen pump | VG, TP, CZ, phenobarbitone, CBZ, VPA, zonisamid, rufinamid 7 years: vagal nerve stimulator | NA | NA | NA | VPA, LV, VG, TP, LM, hormonal treatment |
Epilepsy control | Yes | No | No | Yes | No | NA | Temporary | ||||
Brain MRI (age) | 4 year 8 months | 17 years | NA | NA | 5 years | 7 years and 10 years | 4 months and 5 years | NA | 2 years | 23 months | 1 year |
Atrophy | + | - | - | + | - | + | + | NA | + | - | + |
Periventricular anomalies | - | - | - | + | - | NR | - | NA | + | - | - |
EMG features | Motor and sensory neuropathy | NA | NA | Normal | Normal | NA | NA | NA | NA | NA | NA |
Muscle biopsy anomalies | T2 fibers atrophy | NA | Normal | COX-negative fibers | Few ragged red fibers, nemalin rods | NA | NA | NA | NA | NA | NA |
