Pontocerebellar hypoplasia type 6 (PCH6) is a rare autosomal recessive disease that occurs due to mutations in the mitochondrial arginyl-tRNA synthetase 2 (RARS2) gene. To the best of our knowledge, 23 cases with relatively complete clinical data have been reported thus far. In the present study, a case with PCH6 caused by novel RARS2 mutations is described, in which distinct magnetic resonance imaging (MRI) features were identified. In addition, 23 PCH6 cases found in the literature were reviewed. Early onset hypotonia (43.48%), epileptic seizures (34.78%), encephalopathy (26.08%) and feeding difficulties (17.39%) were common initial symptoms of PCH6. During disease progression, the patients presented refractory epileptic seizures (94.12%), feeding problems (60.87%), severe developmental delay (100%), microcephaly (88.89%) and hyperlactacidemia (76.47%). The clinical features of the present patient were suggestive of PCH6, with early onset epilepsy, feeding difficulties, severe developmental delay, microcephaly, hearing loss and hyperlactacidemia. According to available MRI data from 20 reported cases with PCH6, the characteristic finding in MRI was pontocerebellar dysplasia or progressive cerebral/pontocerebellar atrophy in 16 cases, while 4 cases did not present pontocerebellar hypoplasia, and no basal ganglia involvement was observed in any of the cases. Distinctive MRI features were also identified in the present case, including pontocerebellar preservation after 1 year of age, as well as a high diffusion-weighted imaging signal suggesting intracellular edema in the cerebellar hemispheres, basal ganglia, thalamus and corpus callosum. Progressive loss of cerebral white matter and cortical volume were common features shared by all patients. In conclusion, in the present study, two novel heterozygous mutations were identified in RARS2, namely c.1718C>T(p.Thr573Ile) and c.991A>G (p.Ile331Val). Thus, the present case enriched the phenotypic and genotypic spectrum of the RARS2 mutations.
Keywords: RARS2; magnetic resonance imaging; pontocerebellar hypoplasia type 6.