Table 1 Clinical, molecular and MRI characteristics of genetically proven cases of RNase T2-deficient leukoencephalopathy and present case
Cases | Study | Nucleotide position change | Zygosity | Clinical presentations | MRI/ CT Findings |
|---|---|---|---|---|---|
1–7 | Henneke et al-2009 | 1,2: 550 T > C 3,4: 87-1341_147 + 1181del2583 5: 262–2 A > G 6: 332 + 1delG 7: 50_64del 567G4A | Cases 1–6: Homozygote Case 7: Compound heterozygote | -Static encephalopathy -Normo/microcephaly -Psychomotor delay | Brain MRI: - Multifocal bilateral white matter lesions - Anterior temporal subcortical cysts -Focal temporal horn enlargement - Scattered intra-cranial calcifications - Gyral abnormalities |
8 | Davide Tonduti et al-2016 | c.550 T > C/p.Cys184Arg | Homozygote | -Age of onset: 11 months old -Generalized epileptic seizures -Psychomotor retardation -Bilateral spasticity -Truncal hypotonia -Poor social contact -Optic atrophy, and nystagmus -Microcephaly | Brain CT scans: (at 8 and 11 months of age): -Cerebral and cerebellar atrophy -Calcifications in the globus pallidus and cerebellum -White matter hypodensities in brain CT brain |
9 | Davide Tonduti et al-2016 | c.550 T > C/p.Cys184Arg | Homozygote | -Age of onset: 15 months old -Psychomotor delay, Developmental progress at 5 years of age, Attending a school with learning difficulties -Last follow-up (20 years): -Normally grown male -Speak simple sentences -Mobile without aids -Visual and auditory function: normal -No seizures. | Brain CT: -Basal ganglia and cerebellum calcifications - Mild cerebral and cerebellar atrophy - Multifocal symmetrical subcortical white matter signal changes -Temporal and frontal lobes small cysts Brain MRI (at age 20 years): - Minimal cerebellar and cerebral atrophy -multifocal, symmetric T2 hyperintensities in the periventricular and subcortical white matter -Small cysts in the temporal lobes with larger cystic areas in both frontal lobes Last brain CT: no calcifications. |
10 | Davide Tonduti et al-2016 | paternally: c.397_399delAAG/p.Lys133del maternally: c.145G > T/p.Glu49 | Compound heterozygote | -Age of onset: 3 months old Microcephaly, pyramidal and extrapyramidal impairment, startle reaction, well social interaction, developmental progress in terms of head control at age 23 months, able to crawl and babbling 7 months later -Last follow-up (3 years of age): -Stable neurologic condition, severe spastic dystonic tetraplegia | Brain MRI (At 3 months of age): -Significant multifocal white matter abnormalities in periventricular and deep areas particularly in frontotemporal region -Follow up (15 months): white matter swelling decreased but the same white matter abnormalities Brain CT (13 months): extensive corticosubcortical cerebellar calcifications -Punctuate calcifications in the basal ganglia |
11 | Davide Tonduti et al-2016 | c.2delT/p.Met1? | Homozygote | -Age of onset: 6 weeks old with unexplained fever, marked irritability, axial hypotonia and limb hypertonia, disappearance of systemic features with time -Developmental progress: ability to sit (2 years old), standing with support (4 years old), and walking (6 years old) -Last follow-up (11 years old): -Stable motor phenotype -Cognitive evaluation performed (between 3 and 10 years old): increasing difficulties -Autoimmune thyroiditis -Positive antinuclear antibodies -Mildly positive anti-dsDNA antibodies | Initial and follow-up MRI: - Mainly frontotemporal multifocal white matter lesions - Subcortical temporal and frontal cysts |
12 | Davide Tonduti et al-2016 | c.2delT/p.Met1? | Homozygote | -Age of onset: 6 months old -Horizontal nystagmus -Mild psychomotor delay -Spastic paraparesis -Developmental progress: -Walk independently (spastic gait) for short distances -Developmental IQ (21 months old): low for motor functions but normal for language and sociability | Brain MRI(2.5 months of age): - Anterior predominance multifocal hyperintensity on T2 and hypointensity on T1 weighted imaging, - Posterior periventricular and temporal subcortical white matter lesions without cysts - Mild ventricular enlargement |
13 | Present case | c.233C > A | Homozygote | Age of onset: 3.5 month old -Afebrile tonic spasm seizures - Regression in motor milestones -Unable to neck holding - Microcephaly -Spasticity of four extremities, -Hyperreflexia and low frequent clonus in ankle joints -Head lag, truncal hypotonia -Sluggish eye fix and follow Developmental progress (13 and 19 month old): -Improvement in neck holding, sound production, and social interaction but bulbar dysfunction and feeding was with NG-Tube Last follow-up (22 months old) -Previous abilities - Seizures were controlled - Persistent microcephaly, mild axial hypotonia, spastic quadriparesia, bilateral esotropia, and mild ankle joints contracture | Brain CT (5 month old): -Bilateral periventricular hypodencity in deep white matter -Bilateral basal ganglia calcification Brain MRI (5 months old): - Deep white matter hypomyelination - Bilateral frontal white matter demyelination - Bilateral anterior temporal cyst - Splenium of corpus callosum involvement Brain MRI (22 months old): -Deep white matter signal abnormalities (Hypomyelination) -Bilateral frontal white matter demyelination (Demyelination) - Bilateral anterior temporal cysts -Bilateral putamen black dot |