Autosomal recessive spinocerebellar ataxias are a heterogeneous group of neurological disorders that in most cases present with early-onset progressive cerebellar atrophy or hypoplasia, gait imbalance, and poor coordination . This group comprises a large number of rare diseases, with Friedreich ataxia being the most common, followed by ataxia with oculomotor apraxia or ataxia-telangiectasia . The precise etiology and underlying mechanism have only been elucidated in a small group of autosomal recessive cerebellar ataxias.
Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by progressive early-onset cerebellar atrophy, ataxia, severe developmental delay, coarse facial features, macrocephaly, and absence of speech. SCAR20 is caused by loss-of-function mutations in
A 2-year-old girl (II:1) was referred to our pediatric neurology clinic because of delayed developmental milestones. She attained head control at 3 months and could roll over at 7 months, but at 2 years, she was unable to sit alone, walk, and speak meaningful words (the age of the patients was described as corrected age for those under the age of 2 years). She was born at 34 weeks of gestation with a weight of 2,080 g after an eventful pregnancy from non-consanguineous healthy Korean parents. Her family had no history of neurodevelopmental disorders. Her height, weight, and head circumference were 86 cm (25%-50%), 12.1 kg (50%-75%), and 47 cm (25%-50%), respectively. Her physical examination was unremarkable, apart from the observation of distinctive facial features, including high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose (Figs. 1A, B). Her neurologic examination revealed a decreased deep tendon reflex. Metabolic tests, including levels of plasma amino acid, urine organic and amino acids, mucopolysaccharides, and oligosaccharides, were normal. Karyotype, chromosomal microarray and methylation-specific test for Prader–Willi syndrome, and genetic test for
Her younger sibling (II:2) was referred for the evaluation of global developmental delay at 24 months of age. She was unable to sit, crawl, or speak meaningful words. She was born at 34 weeks of gestation, with a weight of 1,810 g. After birth, noninvasive ventilation was required due to mild respiratory insufficiency but was stopped within a few days. At 6 months of age, she underwent adductor tenotomy and close reduction due to developmental dysplasia of the hip. At 2 years of age, examinations revealed that her height, weight, and head circumference were 81.5 cm (50%-75%), 12.1 kg (50%-75%), and 50.5 cm (>97%), respectively. Her neurologic examination was unremarkable. Similar to her older sibling, she presented with distinct facial features (Figs. 1C, D). Brain MRI, which was performed in the neonatal period, revealed multiple linear T1 high signal intensities on both periventricular areas, suggesting non-cavitary periventricular leukomalacia (Fig. 2C). Follow-up brain computed tomography at 24 months of her age revealed a relatively thin corpus callosum and prominent extra-axial fluid (Fig. 2D). Metabolic tests, including levels of plasma amino acid, urine organic and amino acids, mucopolysaccharides, and oligosaccharides, were normal. Chromosomal microarray was also normal. Whole-exome sequencing was performed for the older sibling (II:1) and the parents (I:1 and I:2) after obtaining written informed consent from the parents. The
Herein, we report the case of a Korean family with two siblings with SCAR20 who are carrying homozygous splicing acceptor variants in
The tissue distribution and cellular function of SNX14 protein have been recently investigated.
To date, 19 homozygous and two compound heterozygous pathogenic variants in
This is the first report describing Korean families with SCAR20 carrying homozygous variants in
The authors declare that they do not have any conflicts of interest.
This study was supported by the National Research Foundation of Korea (NRF-2018R1C1B5085985). The authors would like to express their gratitude to all the patients and family.
Conception and design: YJL. Acquisition of data: ARK. Analysis and interpretation of data: GHS, SIL. Drafting the article: GHS, YJL. Critical revision of the article: JML, HB. Final approval of the version to be published: all authors.