Objective: Genetic and clinical analysis in primary cerebral calcification.

Background: Cerebral calcification is associated with a variety of disorders of different aetiologies. To date, the primary form of cerebral calcification is thought to be a genetically and clinically heterogeneous disease with variable penetrance within and between families. There are currently four known genes responsible for primary familial brain calcification, SLC20A2 being the most prevalent one. However, almost half the patients with primary familial brain calcification remain without a genetic diagnosis. 

Methods: In-depth, phenotype-genotype and radiological analysis of patients with cerebral calcifications. Genetic testing was performed using Whole Exome Sequencing. Visual calcification rating of total calcification scores(TCC) was performed by two separate investigators.

Results: We analysed 58 cases of brain calcifications suggestive of Fahr’s syndrome of which 72% presented with primary brain calcification and 28% had secondary forms. Whole exome sequencing was performed in 32 patients and identified a causal mutation in 17.4% of cases. The most frequent gene in this cohort was SLC20A2.  In the familial form, movement disorders (65%), psychiatric (60%) and cognitive symptoms (56%) were most common clinical presentation with high familial and interfamilial variability. In the secondary forms, 12.5% of cases had a mitochondrial disorder presenting with cerebral calcification and 15.5% were due to other pathology. One case presented with isolated, heavy pontine calcification.  TCC scores were highly variable even within family members and there was no correlation with age or progression .

Conclusions: The largest UK series of genetic and clinical analysis of cerebral calcification shows high phenotype variability and calcification patterns, absence of calcification score correlations and contributes with novel mutations. Less than one third of the patients with primary familial brain calcification were found to have a genetic cause suggesting further thorough genetic studies are necessary with potential for the discovery of new causal genes.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-and-clinical-analysis-of-cerebral-calcifications/