What is Brown-Vialetto-Van Laere syndrome?
BVVL is a rare, progressive, neurodegenerative motor neuron disorder that specifically includes palsies (paralysis) of the cranial nerves, and is sometimes referred to as “bulbar palsy.” The name Brown-Vialetto-Van Laere comes from physicians and researchers who described some of the first reported cases (Brown, 1894; Vialetto, 1936; and Van Laere, 1966), all of which also include sensorineural hearing loss. Though sensorineural hearing loss is a primary component of the syndrome, it may not be discovered until late in children due to the mildness of the hearing loss or the more obvious symptoms that manifest first. Progressive bulbar palsy without hearing loss is referred to as Fazio-Londe syndrome.
Onset of symptoms varies from infancy to the third decade. In many cases, children lead a normal life developmentally, disease-free, for years before developing symptoms. Typically, the first symptom is sensorineural deafness. Other examples of nerve degeneration include vocal cord paralysis, ptosis (droopy eyelids), facial weakness, slurred speech, dysphagia (difficulty swallowing), visual difficulty secondary to optic atrophy, neck and shoulder weakness, limb weakness, autonomic dysfunction, and respiratory compromise.
The course of the disease is variable. Until 2010, when a potential therapy (intravenous B2/riboflavin) was attempted after the gene was discovered, some affected individuals gradually got worse while others had plateaus of stable disease throughout their course; however, all cases up to that point had been fatal, with only one-third of all individuals affected with Brown-Vialetto-Van Laere surviving for longer than ten years.
In 2010, a the first gene for BVVL was discovered, elucidating the disease as a possible riboflavin transporter gene mutation. Since then, other genes have been discovered with similar malfunction. In the same year, trial therapy with B2/riboflavin was attempted for the first time, proving to be a potent stabilizer of disease for many patients with the disease.
What is the cause of BVVL?
BVVL is now linked to several genes that cause riboflavin transport deficiency. Several researchers continue to study the exact mechanism, including the creation of a mouse model so that we can better understand the exact reason for the disease. Most genes appear to have an autosomal recessive pattern of inheritance. Gene testing is currently available for any patient suspected of having the disease through Dr. Henry Houlden's lab in the UK.
How common is BVVL?
Throughout the past century, less than 100 cases of Brown-Vialetto-Van Laere have been reported in the literature from families around the world, although those numbers are growing. We continue to have families and/or their physicians contact us through this web site, and we are learning that BVVL is not near as rare as the literature suggests.
How is BVVL diagnosed?
Clinical presentation of hearing loss, other cranial nerve palsies, and lower motor neuron limb involvement raises the possibility of BVVL. However, it is important to be evaluated by a pediatric neurologist who can also test for other treatable metabolic conditions which may present similarly. It is also important to seek a second opinion.
Hearing tests show sensorineural hearing loss, and brainstem auditory evoked potentials (BAER) are abnormal. Magnetic resonance imaging (MRI) of the brain may show hyperintensities, especially in the brainstem, or may show nothing at all. Muscle biopsy results are typically normal or show groups of atrophic fibers suggesting denervation of muscles. Neurophysiologic tests such as EMG and nerve conduction studies also confirm denervation of muscles, both chronic and active. Cerebral spinal fluid (CSF) analysis after lumbar puncture is typical normal or only shows mildly elevated protein.
Although BVVL shares similar features with a family of diseases known as spinal muscular atrophy (SMA), affected individuals that have been tested and reported in the literature were negative for SMA gene mutations.
Any patient suspected of having BVVL should be tested immediately for one of the BVVL genes, the known riboflavin transporter gene mutations. For BVVL genetic testing, please visit http://www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests, under BVVLS, where the details of the lab and services they offer can be found.
However, it is important NOT TO WAIT FOR THOSE RESULTS before starting trial intravenous B2/riboflavin therapy with your doctor if BVVL is strongly suspected. Patients who are treated early in the disease have shown more clinical improvement.
Is there treatment?
There is no certain effective treatment for Brown-Vialetto-Van Laere; however, there have been reports of stabilization or reversal of degeneration with the use of a new B2 Protocol. However, this therapy does not appear to work for all patients. This is a future area of research, why some patients respond to B2 and why some do not.
For further information and instruction on the informal study of Riboflavin therapy, please contact one of the authors, Dr. Bosch, at the University of Amsterdam at email@example.com.
In some past case reports which are less promising, steroids and intravenous immunoglobulins (IVIg) have been tried with little success, typically short periods of stabilization before disease progression. Supportive care and symptomatic treatment such as tracheostomy, assisted ventilation, and gastrostomy are typically offered to patients and their families when therapy is not working.