Clinical Research Directory

Inclusion criteria are: 1. Age of 18 years or over, 2. Clinical diagnosis of Fahr's disease or syndrome. No international accepted diagnostic criteria for Fahr's disease or syndrome exist yet. It is diagnosed mostly based on the clinical presentation. For the present study the following criteria are used: 1. Clinical symptoms consistent with a clinical diagnosis of Fahr's disease or syndrome. 2. Bilateral calcifications of the basal ganglia as seen on the computed tomography (CT) scan of the head. To rule out basal ganglia calcifications due to aging, a CT based calcification score will be used as proposed by Nicolas et al. Calcification is graded from 0 (no calcification) to 5 (serious and confluent) in specific locations of the brain; lenticular, caudate, thalamus nuclei, subcortical white matter, cortex, cerebellar hemispheres, vermis, midbrain, pons, and medulla. The total calcification score (ranging from 0 to 80) is obtained by adding all location-specific points, where a score higher than the age-specific threshold points at Fahr's disease or syndrome. Furthermore, the next criteria are supportive for the clinical diagnosis of PFBC: 3. Frequently, the family history is consistent with autosomal dominant inheritance. A positive family history with at least one relative in the first or second degree with symptoms of PFBC is supportive for the clinical diagnosis of PFBC. 4. The presence of a (likely) pathogenic mutation in one of the PFBC-related genes is supportive for the clinical diagnosis of PFBC. Mutations in up to now 4 known genes are associated with an autosomal dominant pattern of inheritance: solute carrier family 20 member 2 (SLC20A2) (OMIM#213600), xenotropic and polytropic retrovirus receptor 1 (XPR1) (OMIM#616413), platelet-derived growth factor b (PDGFB) (OMIM#615483), and platelet-derived growth factor receptor b (PDGFRB) (OMIM#615007). Autosomal recessively inherited PFBC is associated with mutations in two genes: myogenesis-regulating glycosidase (MYORG) (OMIM#618317) and junctional adhesion molecule 2 (JAM2) (OMIM#618824). Exclusion criteria are: 1. unable or unwilling to sign an informed consent, 2. severe renal impairment (estimated glomerular filtration rate (eGFR) of \<30 ml/min/1.73m2 calculated using CKD-EPI equation), 3. contraindication to receiving oral medication (for example severe dysphagia), 4. known abnormality of the oesophagus that would interfere with the passage of the drug (for example oesophageal strictures or achalasia), 5. known sensitivity to etidronate, 6. pregnancy, women with an active pregnancy wish \<1 year, or women who are breastfeeding at the time of inclusion, 7. inability to undergo a Dutch neuropsychological assessment (for example, non-fluent Dutch speakers or severe visual, hearing or motor impairment), 8. any other medical or social condition that puts the subject at risk of harm during the study or might adversely affect the interpretation of the study data, 9. use of bisphosphonates during the last 5 years, 10. hypocalcaemia (calcium \<2.20 mmol/L), 11. 25-OH vitamin D deficiency \<35 nmol/L. After correction of hypocalcaemia or vitamin D deficiency, a participant is again suitable for participation.