Genetic background of neurological disorders with basal ganglia calcification
Yektay Farahmand, Maha LU
; Wallenius, Joel
LU
; Wasselius, Johan
LU
; Gråhamn, Olof
LU
; Puschmann, Andreas
LU
and Ilinca, Andreea
LU
(2025)
In Journal of Neurology
272(9).
p.1-11
- Abstract
BACKGROUND: Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC.
METHODS: We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities,... (More)
BACKGROUND: Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC.
METHODS: We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history.
RESULTS: Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease.
CONCLUSIONS: Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.
(Less)
- author
- Yektay Farahmand, Maha
LU
; Wallenius, Joel
LU
; Wasselius, Johan
LU
; Gråhamn, Olof
LU
; Puschmann, Andreas
LU
and Ilinca, Andreea
LU
- organization
- publishing date
- 2025-09-14
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Male, Female, Basal Ganglia Diseases/genetics, Calcinosis/genetics, Middle Aged, Adult, Aged, Sodium-Phosphate Cotransporter Proteins, Type III/genetics, Nervous System Diseases/genetics, Young Adult, Mitochondrial Diseases/genetics, Glycoside Hydrolases
- in
- Journal of Neurology
- volume
- 272
- issue
- 9
- article number
- 632
- pages
- 1 - 11
- publisher
- Springer
- external identifiers
-
- scopus:105016055640
- pmid:40947452
- ISSN
- 1432-1459
- DOI
- 10.1007/s00415-025-13344-1
- language
- English
- LU publication?
- yes
- additional info
- © 2025. The Author(s).
- id
- b7b10e22-8b8e-4212-aab5-37a27a4d9361
- date added to LUP
- 2026-09-28 19:04:59
- date last changed
- 2026-09-30 03:15:19
@article{b7b10e22-8b8e-4212-aab5-37a27a4d9361,
abstract = {{<p>BACKGROUND: Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC.</p><p>METHODS: We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history.</p><p>RESULTS: Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease.</p><p>CONCLUSIONS: Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.</p>}},
author = {{Yektay Farahmand, Maha and Wallenius, Joel and Wasselius, Johan and Gråhamn, Olof and Puschmann, Andreas and Ilinca, Andreea}},
issn = {{1432-1459}},
keywords = {{Humans; Male; Female; Basal Ganglia Diseases/genetics; Calcinosis/genetics; Middle Aged; Adult; Aged; Sodium-Phosphate Cotransporter Proteins, Type III/genetics; Nervous System Diseases/genetics; Young Adult; Mitochondrial Diseases/genetics; Glycoside Hydrolases}},
language = {{eng}},
month = {{09}},
number = {{9}},
pages = {{1--11}},
publisher = {{Springer}},
series = {{Journal of Neurology}},
title = {{Genetic background of neurological disorders with basal ganglia calcification}},
url = {{http://dx.doi.org/10.1007/s00415-025-13344-1}},
doi = {{10.1007/s00415-025-13344-1}},
volume = {{272}},
year = {{2025}},
}