Last modified: 2018-09-09
Abstract
Introduction
Cerebellar involvement can be isolated or part of diffuse brain involvement
The Manifestations are protean and depends on age of child and stage of disease process. Clue to diagnoses is cerebellar atrophy.
Method
Children with undiagnosed neurological disorder after initial clinical, ophthalmic evaluation and metabolic screening (including lactate) in whom MRI brain was demonstrating Cerebellar atrophy were included in the study for Clinical Exome Sequencing. We present report of 26 children analysed between 2016 to 2018.
Result
15 boys and 11 girls, aged from 2 months to 10 years (median age 3 years).14 children were born to consanguineous parents. Common manifestations included developmental delay (Global15, motor 3), central hypotonia(9),walking difficulties(8), movement disorders(6), nystagmus(5).
The clinical diagnoses with clinical examination and neuroimaging included Global developmental delay with cerebellar involvement(10),Cerebellar ataxia(8), Pontocerebellar hypoplasia spectrum(4), spinocerebellar ataxia (2),INAD/NBIA(1) and Marinesco sjogren(1).
16 pathogenic variants of genes were noted on genetic analysis which were SIL1 (3, Marinesco sjogren),PLA2G6 (4,INAD/NBIA),ITPR1(2,spinocerebellar ataxia), KIAA1279(1, Glodberg spritzer megacolon), SERAC1(1, MEGDEL Syndrome), ACO2(1,Aconitase deficiency),NUBPL(1, Mitochondrial complex 1 deficiency), RNASET2(1,Leucoencephalopathy,cystic,without megalencephaly), KCTD7(1,Progressive Myoclonic Epilepsy-3). Uncertain significance(4) and none detected(6) included the rest.
Conclusion
In 16/26 cases Clinical exome sequencing provided a definitive answer. Cerebellar atrophy provides a unifying handle for varied genetic aetiologies.