| Current study | Current study | Individual described by Kitao et al., 2020 |
---|---|---|---|
Patient | Patient 1 | Patient 2 | Proband |
Age at last review | 10Â years | 14Â years | 29Â years |
Gender | Male | Male | Male |
Country of parental origin | Mother: Irish Father: Irish-Canadian | Mixed Northern European-Italian | Japan |
Birth weight/gestational age | 3.2Â kg / 41Â weeks | 3.3Â kg / 40Â weeks | NR |
Current height (centile) |  < 1%ile | 133 cm (< 1%ile) | 130 cm (< 1%ile) |
Current weight (centile) | 19.5 kg (< 1%ile) | 30 kg (< 1%ile) | 21 kg (< 1%ile) |
Feeding/swallowing difficulties | Failure to thrive from an early age | Failure to thrive and diarrhea (age 4) | NR |
Respiratory function | Recurrent episodes of croup, recurrent pneumonias, moderate obstructive sleep apnea | Nocturnal CPAP, restrictive lung disease | Respiratory failure at age 20 requiring tracheostomy with positive-pressure ventilation (TPPV) |
G-tube and age at dependency | No | Age 12 | NR |
Developmental/academic history | Grade 5, above average | Grade 9, grade A average | NR |
Communication | Excellent vocabulary and spelling, severe dysarthria | Excellent written communication, severe dysarthria | No dysarthria |
Gross motor | Sat 7–8 months, crawled 18 months, cruised 2 years, ambulated with walker until 9 years | Delays in rolling, sitting, crawling, standing, walked at 14 months, ambulated until 12 years | Walked at 2.5 years, ambulated until 12 years |
Fine motor | No pincer grasp, severely limited by hand contractures | Severely limited by hand contractures | Difficult to assess due to muscle weakness and contractures |
Functional status | Non-ambulatory (wheel-chair dependent), can use fork with assistance, fully dependent for most ADLs | Non-ambulatory (wheel-chair dependent), fully dependent for ADLs, required 24-h care | Non-ambulatory at 12Â years |
Facial weakness | Dysarthria, lower facial weakness | Myopathic facies, mild bilateral ptosis, dysarthric speech | Weakness of facial muscles |
Tongue fasciculations | Yes | Yes (with associated atrophy) | No |
Axial hypotonia | Significant (unable to sit unsupported for 20Â s) | Significant (unstable when leaning forward in his chair) | Decreased tone |
Appendicular hypertonia/spasticity | Moderate in legs bilaterally | Mild | NR |
Muscle weakness | Generalized weakness, distal more than proximal | Generalized weakness, distal more than proximal | Distal muscle weakness |
Muscle atrophy | Generalized atrophy, most notable of thenar and hypothenar eminences | Generalized atrophy, most notable in fingers | Generalized muscle atrophy |
Sensory exam | Intact vibration, proprioception mildly decreased | Pain and temperature preserved, vibration and proprioception mildly decreased | Impairment in all modalities distally |
Deep tendon reflexes | Absent throughout | 1 + throughout | Absent throughout |
Extensor plantar response | Bilaterally extensor | Bilaterally extensor | Absent |
Scoliosis | Severe scoliosis with a Cobb angle of 75 degrees | Marked left-sided thoracic scoliosis | Severe scoliosis, Cobb angle of 71 degrees |
Contractures | Bilateral club feet at birth, severe hand contractures | Severe finger, knee, ankle contractures | Hand contractures |
Cardiac function | Echocardiogram (age 9): normal | Normal | NR |
Other | CSF, CPK, serum neuromuscular antibody panel, PMP22, MPZ, ERG2, LITAF, PRX, NFL sequencing, chromosomal microarray, and mitochondrial DNA sequencing: negative | Karyotype, Fragile X, FISH and methylation studies for Prader-Willi and Angelman syndromes, CPK, sequencing of PRX, PMP22, EGR2, MPZ and GJB1: negative | Comprehensive gene analysis of hereditary peripheral neurological diseases by next-generation sequencing: negative |
Brain MRI | Several non-specific tiny white matter hyperintensities in the centrum semiovale and peritrigonal regions bilaterally | Non-specific left peritrigonal increased T2 and FLAIR signal | Normal |
Spine MRI | Normal | Normal | NR |
EMG/NCS | Severe axonal loss and slowed conduction velocity (Table 1) | Severe axonal loss and slowed conduction velocity (Table 1) | Decreased compound muscle action potential amplitudes and reduced motor nerve conduction velocity with absent sensory nerve action potentials |
SETX (NM_015046.5) | c.23C > T (de novo) | c.23C > T (de novo) | c.23C > T (de novo) |
Genomic position (Hg19) | chr9:135224793G > A | chr9:135224793G > A | chr9:135224793G > A |
Predicted effect on protein | p.Thr8Met | p.Thr8Met | p.Thr8Met |
Type of mutation | Missense | Missense | Missense |