Table 4 The clinical and genetic features of the previously reported cases with FARS2 mutations affected by spastic paraplegia
References | Subject | Ethnicity | Consanguinity | Gender | Seizures and age of onset | Brain MRI | Other clinical phenotypes | Death of age | FARS2 variants |
|---|---|---|---|---|---|---|---|---|---|
Yang et al. [19] | 1 | Chinese | Yes | F | No | Normal | Progressive lower limb spasticity, pyramidal weakness with hyperreflexia, extensor plantar responses, and scissors gait | Alive at 41 years of age | p.D142Y (hom) |
2 | Chinese | Yes | M | No | Normal | Progressive lower limb spasticity, pyramidal weakness with hyperreflexia, extensor plantar responses, and scissors gait | Alive at 30 years of age | p.D142Y (hom) | |
3 | Chinese | Yes | F | No | Normal | Progressive lower limb spasticity, pyramidal weakness with hyperreflexia, extensor plantar responses, and scissors gait | Alive at 26 years of age | p.D142Y (hom) | |
4 | Chinese | Yes | F | No | Normal | Progressive lower limb spasticity, pyramidal weakness with hyperreflexia, extensor plantar responses, and scissors gait | Alive at 23 years of age | p.D142Y (hom) | |
Vantroys et al. [20] | 5 | NA | No | M | Convulsive seizures, 19 months | Slight cortical atrophy at 20 months; Bilateral, round, focal T2-hyperintense lesions in the anterior part of the mesencephalon at 17 years | Increased lactate, developmental delay, spastic paraplegia, neurogenic bladder, and sphincter dyssynergia | Alive at 19 years of age | p.A154V/p.P361L (het) |
6 | NA | NA | F | No | Symmetrical T2 hyperintensities of the posterior tegmentum at 17 months; More extensive T2 hyperintense lesions at the tegmentum and periaqueductal gray matter at 6 years; Near resolution of the tegmental lesions but new T2 hyperintense lesions bilaterally in the anterior inferior thalamus and signs of cerebellar atrophy at 15 years | Delayed motor development, spastic paraplegia | Alive at 15 years of age | p.V174del/p.P361L (het) | |
Vernon et al. [8] | 7 | NA | NA | F | Seizure, 2 months | Normal | Globally delayed development, mild facial dysmorphism, an elevated lactate level, truncal hypotonia with brisk extremity reflexes throughout, and an intermittent intention tremor | Alive at 5 years of age | p.R419C/a 116 kb microdeletion (het) |
8 | NA | NA | M | Seizures, only within 6 weeks after birth | Two small foci of T2/FLAIR hyperintensity involving the periventricular white matter and deep white matter of the right posterior frontal lobe | Delayed development, cerebral palsy, metabolic acidosis, truncal hypotonia, dysarthric speech, and a mild intention tremor | Alive at 13 years of age | p.R419C/a 116 kb microdeletion (het) | |
Almannai et al. [6] | 9 | North American | No | F | No | Brain atrophy | Developmental delay, spastic paraplegia | Alive at 20 years of age | p.H159P/p.R419C (het) |
10 | North American | No | F | No | NA | Developmental delay, spastic paraplegia | Alive at 17 years of age | p.H159P/p.R419C (het) | |
Sahai et al. [21] | 11 | Northern European and Ashkenazi Jewish | No | M | No | Abnormal signal hyperintensities in the bilateral dentate nuclei | Spasticity in lower extremities | Alive at 9 years of age | p.Q216X/p.P136H (het) |
Meszarosova et al. [22] | 12 | Czech Roma | No | M | No | Normal | Gait impairment, progressive limb spasticity, hyperreflexia, pes cavus | Alive at 22 years of age | p.P361L/exons 1–2 microdeletion (het) |
Forman et al. [23] | 13 | Irish | No | M | No | Normal | Delayed walking, tremor in the upper limbs, dysphonia; Spasticity, weakness, brisk deep tendon reflexes, extensor plantar responses, and clonus in the lower limbs | Alive at 13 years of age | p.G141E/an 75 kb microdeletion (het) |
14 | Irish | No | F | No | Normal | Delayed walking, tremor in the upper limbs; Spasticity, weakness, brisk deep tendon reflexes, extensor plantar responses, and clonus in the lower limbs | Alive at 7 years of age | p.G141E/an 75 kb microdeletion (het) |