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Table 1 Clinical, molecular and MRI characteristics of genetically proven cases of RNase T2-deficient leukoencephalopathy and present case

From: RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant

CasesStudyNucleotide position changeZygosityClinical presentationsMRI/ CT Findings
1–7Henneke et al-20091,2: 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
8Davide Tonduti et al-2016c.550 T > C/p.Cys184ArgHomozygote-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
9Davide Tonduti et al-2016c.550 T > C/p.Cys184ArgHomozygote-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.
10Davide Tonduti et al-2016paternally: c.397_399delAAG/p.Lys133del maternally: c.145G > T/p.Glu49Compound 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
11Davide Tonduti et al-2016c.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
12Davide Tonduti et al-2016c.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
13Present casec.233C > AHomozygoteAge 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