Table 2 The clinical and genetic features of our patients and the previously reported cases with FARS2 mutations affected by early-onset encephalopathy
References | Subject | Ethnicity | Consanguinity | Gender | Seizures and age of onset | Brain MRI | Other clinical phenotypes | Death of age | FARS2 variants |
|---|---|---|---|---|---|---|---|---|---|
This study | 1 | Chinese | No | M | No | Long T1 and long T2 signal shadows in the brain parenchyma of bilateral cerebral hemispheres, cortical thinning, long T1 and long T2 signal shadows in the bilateral external capsule, DWI high signal shadows in the white matter around the posterior horn of bilateral lateral ventricles, enlargement of the ventricles, widened and deepened cerebral sulci and fissure, widened subarachnoid spaces in frontal, parietal, and temporal regions | Hypoxic-ischemic encephalopathy, hypotonia of the limbs, a high lactate level | 37 days | p.G309S/p.G315R (het) |
2 | Chinese | No | F | No | Unclear corticomedullary demarcation of the bilateral cerebral hemispheres, long T1 and long T2 signal shadows in the bilateral frontal, parietal and occipital lobes, enlargement of the ventricles, widened cerebral sulci and fissure | Hypoxic-ischemic encephalopathy, hypotonia of the limbs, feeding difficulties, developmental delay and abnormal liver function | 34 days | p.G309S/p.G315R (het) | |
Shamseldin et al. [16] | 3 | Saudi | Yes | F | Seizures, myoclonus, NA | Similar to MRI findings of Leigh syndrome | Muscle weakness, developmental delay, lactic acidosis | 22 months | p.Y144C (hom) |
Elo et al. [18] | 4 | Finnish | No | F | Myoclonic jerks, 2 days | Severe central and cortical atrophy with slight bilateral signal increase in the putamina | Elevated lactate, microcephaly, narrowed, and atrophic gyri | 8 months | p.I329T/p.D391V (het) |
5 | Finnish | No | F | Seizures, 4 days | NA | Elevated lactate | 21 months | p.I329T/p.D391V (het) | |
Almalki et al. [10] | 6 | White British | No | M | Infantile spasms, 6 months | Symmetrical subcortical white matter lesions with thinning of the anterior and genu of the corpus callosum | Developmental delay, small, round, anteriorly rotated ears, and a broad nasal root | Alive at 30 months of age | p.D325Y/an 88 kb microdeletion (het) |
Cho et al. [12] | 7 | Korean | No | M | Generalized tonic–clonic seizures, 3 months | A diffusely atrophic brain at 3 months; Progression of atrophic changes and myelination delay at 6 months | Hypotonia, delayed motor development, spastic four extremities, and increased deep tendon reflexes | Alive at 3 years of age | p.G309S (hom) |
8 | Korean | No | F | Myoclonic movement starting from the right hand and being generalized to the entire body, 4 months | A thin corpus callosum and generalized brain atrophy | NA | Alive at 17 months of age | p.G309S (hom) | |
9 | Korean | No | M | Infantile spasms, 4 months | Mild brain atrophy | Abnormal liver function, an elevated lactate level | 8 months | p.G309S (hom) | |
10 | Korean | No | F | Generalized tonic–clonic seizures, 3 months | Mild brain atrophy | Abnormal liver function, an elevated lactate level | 4 months | p.G309S (hom) | |
Raviglione et al. [7] | 11 | Romanian | No | M | Infantile spasms, 3 months | Microcephaly, enlargement of frontal subarachnoid spaces, and lateral ventricles due to a reduction in volume of the cerebral white matter, slight hyperintensity of hemispheric white matter on T2-weighted images, thin corpus callosum, thinning of the cortical rim | Psychomotor delay, microcephaly, widely spaced eyes, large ears, bilateral divergent strabismus with visual impairment, and bilateral horizontal nystagmus, axial hypotonia and mild distal hypertonia | Alive at 3 years of age | p.R386G/a 134 kb microdeletion (het) |
Almannai et al. [6] | 12 | Arab | Yes | F | Seizures, NA | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | 23 months | p.Y144C (hom) |
13 | Arab | Yes | F | Seizures, NA | Brain atrophy | Developmental delay, microcephaly, liver disease, elevated lactate | 3 months | p.Y144C (hom) | |
14 | Arab | Yes | M | Seizures, 1 month | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | Alive at 2 years of age | p.Y144C (hom) | |
15 | Arab | NA | F | Seizures, 2 months | NA | Developmental delay, elevated lactate | NA | p.Y144C (hom) | |
16 | Arab | No | F | Seizures, 1 month | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | Alive at 1 year of age | p.Y144C (hom) | |
17 | Arab | Yes | M | Seizures, 1 month | Thin corpus callosum | Developmental delay, liver disease, elevated lactate | 3 months | p.Y144C (hom) | |
18 | Arab | No | F | Seizures, 1 month | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | Alive at 13 months of age | p.Y144C (hom) | |
19 | Arab | Yes | F | Seizures, 5 months | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | 2 years | p.Y144C (hom) | |
20 | Arab | Yes | F | Seizures, 1 month | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | Alive at 4.5 months of age | p.Y144C (hom) | |
21 | Arab | Yes | F | Seizures, 20 days | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | 4 months | p.Y144C (hom) | |
22 | Arab | Yes | F | Seizures, 25 days | Brain atrophy, thin corpus callosum | Developmental delay, microcephaly, liver disease, elevated lactate | 3.5 months | p.Y144C (hom) | |
23 | Arab | Yes | F | No | NA | Liver disease, elevated lactate | 2 days | p.V177D/p.Y144C (het) | |
24 | Spanish | NA | F | NA | NA | Elevated lactate | NA | p.G309S/p.R153G (het) | |
Barcia et al. [15] | 25 | French and Chinese | No | F | No | Mild ventriculomegaly | Axial hypotonia, developmental delay, and spastic tetraparesis | Alive at 8 years of age | p.R419H/p.S426* |
26 | French | No | F | Myoclonic focal and generalized seizures, 19 months | Marked ventriculomegaly, enlargement of the subarachnoid spaces due to white matter loss, especially in the Sylvian fissures, abnormal T2 hyperintensities in the lentiform nuclei and dorsal brainstem, cerebellar atrophy | Global hypotonia, psychomotor delay, mild scoliosis, spastic tetraparesis, and severe muscular atrophy predominating on inferior limbs | Alive at 16 years of age | p.R330H/p.L371F (het) | |
27 | French | No | M | Myoclonic generalized and focal seizures, 1 year | Moderate ventriculomegaly and enlargement of the subarachnoid spaces; Dentate nuclei, brainstem and pallidal T2 hyperintensity | Severe psychomotor delay, global hypotonia and lumbar mild scoliosis | Alive at 5 years of age | p. R330H/p.L371F (het) |