Objective: To describe dystonia in a PFBC cohort

Background: Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by calcium deposition in basal ganglia. Dystonia is reported in up to 20% of cases in large series, with limited characterization. Mutations in one of the 7 causative genes can be found in almost 50% of cases, with an autosomal dominant (SLC20A2, XPR1, PDGFB, PDGFRB) or recessive (MYORG, JAM2, CMPK2) inheritance

Method: Examination of a cohort of 65 PFBC patients from a single center, with special focus on dystonic manifestations; genetic testing (NGS)

Results: Dystonic features were observed in 15/65 patients (23%, mainly females, mean onset 47 years). Dystonia was observed in 9 patients (2 with paroxysmal attacks) and tremor in 11. Upper limbs were involved in 2/3 of patients, followed by facial/cervical dystonia. Parkinsonism and brisk reflexes were frequently associated features. Psychiatric or cognitive symptoms were found in about half of the patients (Tab.1).

Genetic analysis was negative in 6 patients (40%); pathogenic mutations were found in 7 subjects (46.6%; 3 SLC20A2, 1 PDGFB, 1 PDGFRB and 2 MYORG); 2 tests are still ongoing.

Dystonia was the most prominent feature in 4 cases (Tab 2 for details):

1) severe laryngeal and oromandibular dystonia with blepharospasm (Meige syndrome; genetic results not available);

2) blepharospasm, oromandibular, cervical and laryngeal dystonia with parkinsonism (PDGFB gene mutation (p.Arg100Cys);

3) paroxysmal dystonic attacks of the right hand lasting 1 minute, triggered by physical exercise and emotional stress occurring several times a day, with good response to carbamazepine (SLC20A2 gene mutation (p.Leu127Argfs44*);

4) paroxysmal dystonic spasms of facial muscles triggered by chewing and teeth brushing (homozygous MYORG gene mutation (p.Trp426Cysfs*11)

Conclusion: Dystonia is frequent in PFBC and was observed in 23% of our cohort, being the prominent movement disorder in 6% of cases. Dystonia was combined with additional neurological and psychiatric manifestations in most cases, with a progressive course in all but 2 subjects, that showed paroxysmal attacks with various triggers.

Data partially submitted as abstract, Samuel Belzberg 6th International Dystonia Symposium, Dublin Ireland, 2023

References: 1) Tadic V, Westenberger A, Domingo A, Alvarez-Fischer D, Klein C, Kasten M (2015) Primary familial brain calcification with known gene mutations: a systematic review and challenges of phenotypic characterization. JAMA Neurol 72:460–467
2) Balck A, Schaake S, Kuhnke NS, Domingo A, Madoev H, Margolesky J, Dobricic V, Alvarez-Fischer D, Laabs BH, Kasten M, Luo W, Nicolas G, Marras C, Lohmann K, Klein C, Westenberger A (2021) Genotype-phenotype relations in primary familial brain calcification: systematic MDSGene review. Mov Disord 36(11):2468–2480

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pfbc-and-dystonia-description-of-a-cohort-and-peculiar-cases/