Fahrís Syndrome is an inherited, genetic disorder
characterized by abnormal deposits of calcium in brain areas which control movement. Calcium deposits in the basal ganglia, cerebral and cortical regions (parts of the brain areas) leading to atrophy. This mineral deposit causes significant neuron (brain cell) loss, leading to motor and mental disabilities.
Inheritance and Genetics in Fahrís Syndrome
The molecular genetics of Fahrís syndrome is under-researched, therefore molecular and genetic evidence is limited. However, the gene IBGC1 has been identified as one of those causing idiopathic basal ganglia calcification. A second locus for the genetic pathophysiology of Fahrís is identified as chromosome 8 and chromosome 2. Fahrís syndrome usually affects individuals in their 40s and 50s though it may sometimes occur in childhood or adolescence. The disease prevalence is less than 1 in 1,000,000.
Symptoms of Fahrís Syndrome
Individuals affected with Fahrís present a range of neurological, neuropsychiatric, memory loss, Parkinsonian and chorea-like symptoms. The clinical features are:
- Neurological disorders Ė seizures, loss of consciousness, spasticity, gait issues, speech impairment, memory loss or dementia-like symptoms, chorea (dance-like movements), athetoid tremors and movements and dystonia (muscle spasms).
- Movement disorders Ė unsteady gait, lurching, slurred speech, clumsiness, involuntary movements and dysphagia (difficulty in swallowing).
- Neuropsychiatric disorders Ė vary from mild to severe symptoms. Individuals may present with mild memory loss to total loss of identity. There may be behavioral and personality changes. Some individuals also present with psychosis.
Etiology / Causes of Fahrís Syndrome
Some of the causes attributed to Fahrís syndrome include:
- Endocrine disorders Ė parathyroid disturbances are associated with Fahrís. Endocrine disorders disturb the bodyís metabolism including serum calcium concentration which can lead to excessive calcification in brain areas. Vitamin D disturbance is also an associated condition.
- Mitochondrial myopathies Ė are also associated with calcium metabolism. The most common radiological finding in mitochondrial myopathies is basal ganglia calcification.
- Dermatological issues Ė are correlated to basal ganglia calcification. One such condition is known as lipoid proteinosis which results in symptoms like seizures, dementia, hair loss, photosensitivity and dwarfism.
- Infectious diseases Ė also play a role in basal ganglia calcification. Infections like HIV, herpes, rubella and toxoplasmosis are associated with Fahrís.
Normal aging also leads to calcification in the basal ganglia in elderly individuals. However, this rarely leads to Fahrís syndrome.
Diagnosis of Fahrís Syndrome
Neurologists and psychiatrists usually evaluate the individual taking into account his/her general health, family genetic history, personal medical and genetic histories. Some of the diagnostic tests involved in Fahrís include:
- Imaging Ė a CT scan is usually recommended to detect calcification. Sometimes an MRI is also necessary.
- Blood tests Ė like serum calcium, phosphorus, manganese and alkaline phosphatase are also recommended.
- CSF analysis Ė cerebrospinal fluid analysis is recommended to check for infections and autoimmune conditions.
Diagnosis of Fahrís requires great skill as many of the symptoms are similar to other neurological and neuropsychiatric disorders. Diagnosis is usually done taking into account clinical symptoms and ruling out other causes.
Management of Fahrís Syndrome
Diverse treatment approaches are used to stabilize individuals with Fahrís syndrome. The goal is mainly to alleviate symptoms and keep the individual comfortable and pain free. Pharmacological drugs are usually used to control anxiety, depression and psychosis. Antiepileptic drugs like Carbamazepine
and Benzipenes are used to control seizures. Antipsychotic agents like lithium are used to alleviate mood swings and depression. However, lithium should be used with caution as it can increase gait issues like lurching and swaying.
Vitamin D-related Fahrís symptoms may be alleviated with doses of alpha hydroxy vitamin D3.
Treatment and management of Fahrís is multidisciplinary involving caregivers, genetic counsellors, psychiatrists, neurologists, endocrinologists and other physicians. There are currently no standard protocols for management of Fahrís. Doctors and health care specialists manage individuals on a case-by-case basis.
While the current research focus is on pathophysiological mechanisms leading to calcification in brain areas, there is also the need to further explore safe treatment options. Many of the drugs used currently are not well tolerated and have side effects impacting hormonal, liver and kidney function. There is a need to evolve treatment modalities that prevent loss of neurological function and degeneration.