Fahr disease

By Marcello Cherchi, MD PhD

For patients

In Fahr disease (FD) calcium accumulates in parts of the brain. Patients with FD can have problems with movement and thinking. If your doctor suspects FD, they may check brain imaging and sometimes tests of balance function. There is no cure.

For clinicians

Overview

Fahr disease (FD) is a rare neurodegenerative disorder in which symmetrical calcification occurs in various brain regions, particularly the basal ganglia and cerebellum. Some cases are idiopathic, others occur in a familial pattern (autosomal dominant or recessive). Clinical presentation includes movement disorders, cognitive and psychiatric disorders and ataxia. Some patients exhibit imbalance but this has not been well studied from the otovestibular perspective. The intracranial calcifications can be identified on head CT. Treatment is supportive.

Introduction

In 1930 the German pathologist, Karl Theodor Fahr (Pirmasens, Germany 1877 – Hamburg, Germany 1945) published a case report of a patient suffering from what was eventually designated Fahr disease (FD) or syndrome (Fahr 1930-1931), though Manyam and colleagues (Manyam et al. 2001) credit Delacour (Delacour 1850) with having published the first description of calcification of the basal ganglia.

FD is a neurodegenerative disorder in which calcium deposits accumulate, usually symmetrically, in various areas of the brain, including the basal ganglia, striatum, internal capsule, cerebral cortex and subcortical regions, thalamus, hippocampus and cerebellum (usually the dentate nucleus).

Some cases of FD occur sporadically, and these are sometimes termed idiopathic basal ganglia calcification (IBGC).

Other cases of FD occur in familial patterns, and these are sometimes called primary familial brain calcification (PFBC).

Epidemiology

FD is rare. Age at symptom onset ranges from the third to the seventh decades (Ellie et al. 1989; Manyam et al. 2001).

Genetics

Several genes have been implicated in the familial form of FD, and exhibit autosomal dominant and autosomal recessive patterns.

Autosomal dominant variants:

  • IBGC1 (OMIM 213600) is caused by a mutation in the solute carrier family 20 member 2 (SLC20A2) on chromosome 8p11.2 (OMIM 158378) (Wang et al. 2012).
  • IBGC4 (OMIM 615007) is caused by a mutation in the platelet-derived growth factor receptor beta (PDGFRB) gene on chromosome 5q32 (OMIM 173410) (Nicolas et al. 2013).
  • IBGC6 (OMIM 616413) is caused by a mutation in the xenotropic and polytropic retrovirus receptor 1 (XPR1) gene on chromosome 1q25.3 (OMIM 605237) (Legati et al. 2015).
  • IBGC5 (OMIM 615483) is caused by a mutation in the platelet-derived growth factor subunit B (PDGFB) gene on chromosome 22q13.1 (OMIM 190040) (Keller et al. 2013; Keogh et al. 2015).

Autosomal recessive variants:

  • IBGC7 (OMIM 618317) is caused by a mutation in the myogenesis regulating glycosidase (MYORG) gene on chromosome 9p13.3 (OMIM 618255) and is transmitted in an autosomal recessive pattern (Yao et al. 2018).
  • IBGC8 (OMIM 618824) is caused by a mutation in the junctional adhesion molecule 2 (JAM2) gene on chromosome 21q21.3 (OMIM 606870) and is transmitted in an autosomal recessive pattern (Cen et al. 2020; Schottlaender et al. 2020).

Clinical presentation

In view of the diverse neuroanatomical areas that can be involved by FD it is unsurprising that the clinical presentation is variable.

Manyam and colleagues (Manyam et al. 2001) conducted a literature and registry review of patients with FD. Of 67 symptomatic patients they documented:

  • 37 (55%) exhibited movement disorders
  • 26 (39%) exhibited cognitive deficits
  • 24 (36%) exhibited speech deficits
  • 24 (36%) exhibited cerebellar dysfunction
  • 21 (31%) exhibited psychiatric disorders
  • 15 (22%) exhibited pyramidal disorders
  • 12 (18%) exhibited gait disorders
  • 11 (16%) complained of pain and other sensory disorders
  • 9 (13%) exhibited genitourinary dysfunction
  • 8 (12%) exhibited gastrointestinal dysfunction
  • 6 (9%) exhibited seizures.

Of the 37 patients with movement disorders they documented:

  • 21 (57%) had parkinsonism
  • 7 (19%) had chorea
  • 3 (8%) had tremor
  • 3 (8%) had dystonia
  • 2 (5%) had athetosis
  • 1 (3%) had orofacial dyskinesias

There are several case reports of FD patients suffering from imbalance (Castello and Pallestrini ; Parasram et al. 2020; Salli et al. 2016; Wang et al. 2015).

Testing: vestibular

As of this writing there were no published reports of instrumented vestibular testing in FD patients.

Testing: other

Scarano and colleagues studied computerized dynamic posturography in a 69 year old male with FD (Scarano et al. 2022). Sensory organization testing showed primarily a vestibular pattern, as shown in the Figure below. This pattern is also found in other disorders with basal ganglionic involvement (even though they are not primary otovestibular diseases).

Figure: Sensory organization testing in a patient with Fahr disease. From Scarano et al. (2022).
Figure: Sensory organization testing in a patient with Fahr disease. From Scarano et al. (2022).

Imaging

The calcifications in Fahr disease are revealed on CT scans.

The Figure below, from Scarano and colleagues (Scarano et al. 2022), shows approximately symmetrical calcification in the basal ganglia and cerebellum.

Figure: Head CT of a patient with Fahr disease. From Scarano et al (2022).
Figure: Head CT of a patient with Fahr disease. From Scarano et al (2022).

Note that abnormal calcium deposits, including in patterns compatible with FD, are found incidentally on anywhere from 0.3% (Koller et al. 1979) to 1.2% (Forstl et al. 1992) of head CTs of patients exhibiting no clinical features of FD.

Differential diagnosis

The differential diagnosis of FD includes basal ganglionic and cerebellar disorders.

Treatment and prognosis

There is no direct therapy for FD. Treatment is supportive.

References

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Page first published on December 6, 2023. Page last updated on December 6, 2023

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