Brown–Vialetto–Van Laere syndrome
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|Brown–Vialetto–Van Laere syndrome|
|Classification and external resources|
The syndrome affects children, adolescents, and younger adults. There is no known cure to the disorder. The prognosis is poor (most patients die within 10 years).
BVVL is marked by a number of cranial nerve palsies, including those of the motor components involving the 7th and 9th-12th cranial nerves, spinal motor nerves, and upper motor neurons (Voudris 2002). Major features of BVVL include facial and neck weakness, fasciculation of the tongue, and neurological disorders from the cranial nerves (Prahbu 2005). The neurological manifestations develop insidiously: they usually begin with sensorineural deafness, progress inexorably to paralysis, and often culminate in respiratory failure. Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts (Prahbu 2005). The first symptoms in nearly all cases of BVVL is progressive deafness, and the first initial symptoms are seen anywhere from one to three years (Sathasivam 2000). Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia, retinitis pigmentosa, epilepsy, mental retardation, and autonomic dysfunction (Sathasivam 2000). Non- neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness, and hypertension.
Genetic testing is able to identify genetic mutations underying BVVL.
There is no known cure to BVVL. Patients require symptomatic treatment and supportive care. This could include gastrostomy feeding and assisted ventilation, while steroids may or may not help patients (Sathasivam 2000).
The first report of BVVL syndrome in Japanese literature was of a woman that had BVVL and showed improvement after such treatments. The patient was a sixty-year-old woman that had symptoms such as sensorineural deafness, weakness, and atrophy since she was 15 years old. Around the age of 49 the patient was officially diagnosed with BVVL, intubated, and then attached to a respirator to improve her CO2 narcosis. After the treatments, the patient still required respiratory assistance during sleep; however, the patient no longer needed assistance by a respirator during the daytime (Hiroshi 2005).
A Dutch group have reported the first promising attempt at treatment of the disorder with high doses of riboflavin.
The clinical course of BVVL can vary from one patient to another. There have been cases with progressive deterioration, deterioration followed by periods of stabilization, and deterioration with abrupt periods of increasing severity (Prahbu 2005).
BVVL syndrome is often found in late childhood and adolescents, however, seven cases have been found with symptoms starting within the first five years (Voudris 2002).
The syndrome can be fatal or protracted for a longer period. There are three documented cases of BVVL where the patient died within the first five years of the disease. On the contrary, at least fourteen patients have survived more than 10 years after the onset of their first symptom, and several cases have survived 20–30 years after the onset of their first symptom (Sathasivam 2000).
Families with multiple cases of BVVL and, more generally, multiple cases of infantile progressive bulbar palsy can show variability in age of disease onset and survival. Dipti and Childs described such a situation in which a family had five children that had Infantile PBP. In this family, three siblings showed sensorineural deafness and other symptoms of BVVL at an older age. The other two siblings showed symptoms of Fazio-Londe disease and died before the age of two (Dipti 2005).
As of 2002, there were thirty-eight known cases of Brown-Vialetto-Van-Laere syndrome worldwide (Voudris 2002). BVVL was first described in a Portuguese family, and has since been described in a number of ethnic groups. Reports have shown that BVVL infects females more than males at a rate of 5:1 respectively. However, males usually exhibit more severe symptoms, an earlier onset of deafness and a tendency to die earlier in life (Voudris 2002).
The syndrome was first described by Charles Brown in 1894; further accounts by Vialetto and Van Laere followed in 1936 and 1966, respectively. There are fewer than 60 cases reported in the medical literature over the 100 odd years since its first description.
- Voudris KA, Skardoutsou A, and Vagiakou EA. Infantile progressive bulbar palsy with deafness. Brain and Development. 24(7):732-735. (2002)
- Sathasivam S, O’Sullivan S, Nicolson A, Tilley PJB, and Shaw PJ. Brown-Vialetto-Van Laere syndrome: Case report and literature review. ALS and Other Motor Neuron Disorders. 1:277-281. (2000)
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- Nair, Pratibhu. Bulbar Palsy, Progressive, with Sensorineural Deafness. The Catalogue for Transmission Genetics in Arabs, CTGA Database. Centre for Arab Genomic Studies. www.cag.org. (2006)
- Dipti S et al. Brown-Vialetto-Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. Brain and Development. 27: 443-446. (2005)
- Hiroshi N et al. A case of Brown-Vialetto-van Laere (BVVL) in Japan. Clinical Neurology. 45(5):357-361. (2005)
- Wilson, John Eastman. Diseases affecting the spinal grey-matter. Diseases of the Nervous System. Boericke and Runyon. (1909)
- Online 'Mendelian Inheritance in Man' (OMIM) 211530
- Green P, Wiseman M, Crow YJ, et al. (March 2010). "Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54". Am. J. Hum. Genet. 86 (3): 485–9. doi:10.1016/j.ajhg.2010.02.006. PMC 2833371. PMID 20206331.
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- Yamamoto, S; Inoue, K., Ohta, K., Fukatsu, R., Maeda, J., Yoshida, Y. and Yuasa, H (2009). "Identification and Functional Characterization of Rat Riboflavin Transporter 2". J Biochem 145 (4): 437–443. doi:10.1093/jb/mvn181. PMID 19122205.
- Bosch, AM; Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR (Nov 2010). "Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment". J Inherit Metab Dis 34 (1): 159–164. doi:10.1007/s10545-010-9242-z. PMC 3026695. PMID 21110228.
- Brown CH. Infantile amyotrophic lateral sclerosis of the family type. J Nerv Ment Dis 1894, 21:707–716.
- Vialetto E. Contributo alla forma ereditaria della paralisi bulbare progressive. Riv Sper Freniat 1936, 40:1–24.
- Van Laere J. Paralysie bulbo-pontine chronique progressive familiale avec surdité. Un cas de syndrome de Klippel-Trenaunay dans la même fratrie – problèmes diagnostiques et génétiques. Rev Neurol 1966, 115:289–295.
- Brown-Vialetto-Van Laere syndrome at the US National Library of Medicine Medical Subject Headings (MeSH)
- Official web site: http://www.bvvlinternational.org
- Brown Vialetto Van Laere syndrome UK Web Site Support and advice to BVVL Patients and their Carers