PP12.16 – 2973: Congenital cerebellar ataxias – Clinical, radiological and genetic considerations

Abstract

Objective Congenital ataxias, according to Harding's classification, represent a subgroup of early onset ataxias. The aim of this study was to evaluate initial clinical presentations, course of the disease and MRI characteristics in order to prioritize future investigations, including appropriate genetic testing. Methods The patients were selected from clinical ataxia registry at the tertiary center (n=51) after excluding patients with cerebellar malformations, later ataxia onset and known underlying disease. We focused on the following points: 1) congenital onset&clinical course 2) associated features 3) occurrence of peripheral neuropathy 4) neuroimaging results. The statistical analysis has done using T test,: version SPSS 15.0. Results There were 14 subjects (27.5%) from 10 kindred presented with congenital onset – 3 families with 2 or more affected members. Clinical characteristics: 86% subjects initially presented with mild to severe generalized hypotonia and global development delay – the mean age of independent walking was 3.9±2.8 and speech 2.5±0.7. Early generalized ataxia is noticed in all subjects, accompanied with nystagmus in 57% and other ocular abnormalities in 64%. Tendon reflexes were present in 79%. The accompanying findings (n=5) were orthopedic – 3, dystonia – 1 and optic atrophy – 1 and axonal motor neuropathy in one. Laboratory and metabolic workup were negative in all subjects. 86% are functioning within normal or low intellectual level. Global cerebellar hypoplasia was the most common MRI finding – in 93% and correlated significantly with clinical findings. Genetic confirmation was obtained for one family – missense mutation in ITPR1 gene. Conclusion The selected group of patient, presented as non-progressive cerebellar ataxia, showed rather uniform clinical characteristics – mostly isolated ataxia “improving” with aging (SARA, t test 0.015). The presence of cerebellar hypoplasia on MRI mostly correlated with phenotypes, suggesting genetic basis of the disease. We assume that new DNA sequencing technologies would help delineate genetic and pathophysiological mechanism of congenital ataxias. Congenital ataxias, according to Harding's classification, represent a subgroup of early onset ataxias. The aim of this study was to evaluate initial clinical presentations, course of the disease and MRI characteristics in order to prioritize future investigations, including appropriate genetic testing. The patients were selected from clinical ataxia registry at the tertiary center (n=51) after excluding patients with cerebellar malformations, later ataxia onset and known underlying disease. We focused on the following points: 1) congenital onset&clinical course 2) associated features 3) occurrence of peripheral neuropathy 4) neuroimaging results. The statistical analysis has done using T test,: version SPSS 15.0. There were 14 subjects (27.5%) from 10 kindred presented with congenital onset – 3 families with 2 or more affected members. Clinical characteristics: 86% subjects initially presented with mild to severe generalized hypotonia and global development delay – the mean age of independent walking was 3.9±2.8 and speech 2.5±0.7. Early generalized ataxia is noticed in all subjects, accompanied with nystagmus in 57% and other ocular abnormalities in 64%. Tendon reflexes were present in 79%. The accompanying findings (n=5) were orthopedic – 3, dystonia – 1 and optic atrophy – 1 and axonal motor neuropathy in one. Laboratory and metabolic workup were negative in all subjects. 86% are functioning within normal or low intellectual level. Global cerebellar hypoplasia was the most common MRI finding – in 93% and correlated significantly with clinical findings. Genetic confirmation was obtained for one family – missense mutation in ITPR1 gene. The selected group of patient, presented as non-progressive cerebellar ataxia, showed rather uniform clinical characteristics – mostly isolated ataxia “improving” with aging (SARA, t test 0.015). The presence of cerebellar hypoplasia on MRI mostly correlated with phenotypes, suggesting genetic basis of the disease. We assume that new DNA sequencing technologies would help delineate genetic and pathophysiological mechanism of congenital ataxias.