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Hereditary and non-hereditary etiologies associated with extensive brain calcification: case series

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Abstract

Cerebral calcification may be caused by several potentially treatable conditions, however, in most cases it does not receive special attention in clinical practice. From the point of view of etiology, the diseases associated with cerebral calcification can be divided into two main groups: idiopathic (mostly incurable) and secondary (potentially treatable). The first group includes mainly the hereditary diseases identified before 2021 (primary familial brain calcification subtypes, previously known as Fahr’s disease or Fahr’s syndrome). In contrast, the second group includes diseases with cerebral calcification that develop generally as a consequence of metabolic/endocrine/autoimmune abnormalities. The aim of our research was to present hereditary and non-hereditary etiologies associated with extensive brain calcification. We compare the detailed clinical, radiological and laboratory results of 6 patients with prominent cerebral calcification identified in our clinic in the last 3 years (idiopathic and secondary etiologies as well). Our research draws attention to the complexity of the etiologies in the context of cerebral calcification. We recommend, beside NGS-based sequence analyses, the application of array comparative genomic hybridization as well, to identify potential genetic etiologies associated with brain calcification.

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Funding

GINOP-2.3.2–15-2 grant (TK and ZM) provided by the National Research, Development and Innovation Office (Hungary). Hungarian Brain Research Program [2017–1.2.1-NKP-2017-00002 NAP VI/4] (PK).

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Author notes

  1. András Salamon and Dénes Zádori contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary

    András Salamon, Dénes Zádori, László Szpisjak, Melinda Lukács, Noémi Szépfalusi, Viola Luca Németh & Péter Klivényi

  2. Division of Clinical Genetics, Department of Laboratory of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

    Anikó Ujfalusi & István Balogh

  3. Department of Neurology, Békés County, Orosháza, Hungary

    Brigitta Bihari

  4. Department of Pediatrics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, H-6725, Hungary

    Zoltán Maróti, Csaba Bereczki & Tibor Kalmár

  5. Department of Medical Genetics, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary

    Emese Horváth

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  1. András Salamon
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  2. Dénes Zádori
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Contributions

AS and DZ examined the patients and wrote the manuscript. VLN and NSZ performed the neuropsychological examination of the patients. Genetic tests and consultations were performed by AU, ZM, EH, IB and TK. PK and CSB had important recommendations to the manuscript. LSZ, ML and BB provided essential assistance in patient involvement and investigation.

Corresponding author

Correspondence to Tibor Kalmár.

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Ethics approval

Written informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article (Regional Human Biomedical Research Ethics Committee of the University of Szeged registration numbers are 150/2014. and 44/2016., respectively). All procedures performed in this study involving human participants were in accordance with the ethical standards of the Regional Human Biomedical Research Ethics Committee of the University of Szeged and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The authors declare that they have no competing/conflict of interests.

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Supplementary Information

Supplementary video 1

Clinical phenotype of case 1 – mos 46,XY,der(11)t(X;11)(p21.1;q14.2)[152]/46,XY[48] (MP4 150,053 kb)

Supplementary video 2

Clinical phenotype of case 2 – SLC20A2 (MP4 76,142 kb)

Supplementary video 3

Clinical phenotype of case 3 – SLC20A2 (MP4 83,455 kb)

Supplementary video 4

Clinical phenotype of case 4 – STX16 (MP4 143,065 kb)

Supplementary video 5

Clinical phenotype of case 5 – Infiltration of the parathyroid gland (MP4 90,431 kb)

Supplementary video 6

Clinical phenotype of case 6 – Secondary hypoparathyroidism (thymectomy) (MP4 88,249 kb)

Supplementary file 1

The gene content of the genetic alteration mos 46,XY,der(11)t(X;11)(p21.1;q14.2)[152]/46,XY[48] found in Case 1 (PDF 488 kb)

Supplementary file 2

Pedigrees and chromatograms of Cases 1–4. (The generation are signed with Roman numbers. The deceased members are crossed. Individuals with symptoms are marked in black. Abbreviations: arrow – genetic test was performed; d. – age of death; E – genetic examination; p – proband; y – year; + or - – the result of the genetic test.) (PDF 1978 kb)

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Salamon, A., Zádori, D., Ujfalusi, A. et al. Hereditary and non-hereditary etiologies associated with extensive brain calcification: case series. Metab Brain Dis 36, 2131–2139 (2021). https://doi.org/10.1007/s11011-021-00790-9

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