Research Publications



Udhayabanu T, Manole A, Rajeshwari M, Varalakshmi P, Houlden H, Ashokkumar B.

Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases.

​J Clin Med. 2017 May 5

Rizzo F, Ramirez A, Compagnucci C, Salani S, Melzi V, Bordoni A, Fortunato F, Niceforo A, Bresolin N, Comi GP, Bertini E, Nizzardo M, Corti S.

Genome-wide RNA-seq of iPSC-derived motor neurons indicates selective cytoskeletal perturbation in Brown-Vialetto disease that is partially rescued by riboflavin.

Sci Rep. 2017 Apr 6

​Allison T, Roncero I, Forsyth R, Coffman K, Le Pichon JB.

Brown-Vialetto-Van Laere Syndrome as a Mimic of Neuroimmune Disorders.

J Child Neurol. 2017 Jan​

Bashford JA, Chowdhury FA, Shaw CE.
Remarkable motor recovery after riboflavin therapy in adult-onset Brown-Vialetto-Van Laere syndrome.

​Pract Neurol. 2016 Oct 24


Udhayabanu T, Subramanian VS, Teafatiller T, Raju KN, Raghavan VS, Varalakshmi P, Said HM, Ashokkumar B.

SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere Syndrome in an Indian patient: first genetically proven case with mutations in two riboflavin transporters.

Clin Chim Acta. 2016 Oct 1

Barile M, Giancaspero TA, Leone P, Galluccio M, Indiveri C.
Riboflavin transport and metabolism in humans.
J Inherit Metab Dis. 2016 Jun 6



Shashi V, Petrovski S, Schoch K, Crimian R, Case LE, Khalid R, El-Dairi MA, Jiang YH, Mikati MA, Goldstein DB

Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing.

Cold Spring Harb Mol Case Stud. 2015 Oct

Petrovski S, Shashi V, Petrou S, Schoch K, McSweeney KM, Dhindsa RS, Krueger B, Crimian R, Case LE, Khalid R, El-Dairi MA, Jiang YH, Mikati MA, Goldstein DB.

Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition.

Cold Spring Harb Mol Case Stud. 2015 Oct 1

Intoh A, Suzuki N, Koszka K, Eggan K
SLC52A3, A Brown-Vialetto-van Laere syndrome candidate gene is essential for mouse development, but dispensable for motor neuron differentiation.
Hum Mol Genet. 2016 Mar 13

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Menezes MP, O'Brien K, Hill M, Webster R, Antony J, Ouvrier R, Birman C,Gardner-Berry K.
Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency.  
Dev Med Child Neurol. 2016 Feb 25.

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BVVL Audiology DMCN 2016 Menezes-2.pdf
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Horoz OO, Mungan NO, Yildizdas D, Herguner O, Ceylaner S, Kor D, Waterham H, Coskun T.
Brown-Vialeto-Van Laere syndrome: two siblings with a new mutation and dramatic therapeutic affect of high-dose riboflavin
J Pediatr Endocrinol Metab. 2015 Oct. 7

Davis A, Josifova D, Lloyd-Owen S, Radunovic A, Swash M.
Brown-Vialetto-Van Laere syndrome: a 28 year follow up
J Neurol Neurosurg Psychiatry. 2015 Oct. 6.

Chandran R, Alexander M, Naina P, Balraj A.
Auditory neuropathy spectrum disorder with Brown-Vialetto-Van Laere syndrome: challenges in hearing rehabilitation.
J Laryngol Otol. 2015 May, 129(5): 504-8. doi: 10.1017/S0022215114003375 Pub Med

Subramanian VSKapadia RGhosal ASaid HM.
Identification of residues/sequences in the human riboflavin transporter-2 that is important for function and cell biology.  Nutr Metab (Lond). 2015 Mar 14;12:13. doi: 10.1186/s12986-015-0008-3. eCollection 2015.

Varadarajan PThayanathi VPauline LC.
Fazio Londe syndrome: A treatable disorder.
Ann Indian Acad Neurol. 2015 Jan-Mar;18(1):87-9. doi: 10.4103/0972-2327.144283.

Cosgrove J, Datta S, Busby M.
Adult onset Brown-Vialetto-Van Laere syndrome with opsoclonus and a novel heterozygous mutation: A case report. Clin Neurol Neurosurg. 2014 Nov 4; 128C:1-3. doi:10.1016/j.clineuro.2014.10.016.

Manole A1, Fratta P, Houlden H. Recent advances in bulbar syndromes: genetic causes and disease mechanisms.Curr Opin Neurol. 2014 Oct;27(5):506-14. doi: 10.1097/WCO.0000000000000133.

Foley AR1Menezes MPPandraud AGonzalez MAAl-Odaib AAbrams AJSugano KYonezawa AManzur AYBurns JHughes IMcCullagh BGJungbluth HLim MJLin JPMegarbane AUrtizberea JAShah AHAntony JWebster RBroomfield ANg JMathew AAO'Byrne JJForman EScoto MPrasad M, O'Brien KOlpin SOppenheim MHargreaves ILand JMWang MXCarpenter KHorvath RStraub VLek MGold WFarrell MOBrandner SPhadke R, Matsubara KMcGarvey MLScherer SSBaxter PSKing MDClayton PRahman SReilly MMOuvrier RAChristodoulou JZüchner SMuntoni FHoulden H.   Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2.Brain. 2014 Jan;137(Pt 1):44-56. doi: 10.1093/brain/awt315. Epub 2013 Nov 19.


Nalini A, Pandraud A, Mok K, Houlden H.  Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome. J Neurol Sci. 2013 Nov 15;334(1-2):119-22. doi: 10.1016/j.jns.2013.08.003. Epub 2013 Aug 13.

Ciccolella M1Corti SCatteruccia MPetrini STozzi GRizza TCarrozzo RNizzardo MBordoni ARonchi DD'Amico ARizzo CComi GPBertini E.  

Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations.  J Med Genet. 2013 Feb;50(2):104-7. doi: 10.1136/jmedgenet-2012-101204. Epub 2012 Dec  14.

Yonezawa A, Inui K.  Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52.  Mol Aspects Med. 2013 Apr-Jun;34(2-3):693-701. doi: 10.1016/j.mam.2012.07.014.

Yao Y1Yonezawa AYoshimatsu HOmura TMasuda SMatsubara K.

Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice. Eur J Pharmacol. 2013 Aug 15;714(1-3):281-7. doi: 10.1016/j.ejphar.2013.07.042. Epub 2013 Aug 1.

Ghosal A1Said HM.

Mechanism and regulation of vitamin B2 (riboflavin) uptake by mouse and human pancreatic β-cells/islets: physiological and molecular aspects. Am J Physiol Gastrointest Liver Physiol. 2012 Nov 1;303(9):G1052-8. doi: 10.1152/ajpgi.00314.2012. Epub 2012 Aug 23.

Bosch AM, Stroek K, Abeling NG, Waterham HR, Lodewijk I, Wanders RJ. The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives. Orphanet Journal of Rare Diseases. 2012 7:83 doi: 10.1186/1750-1172-7-83. Epub 2012 Oct 29.

Johnson JO, Gibbs JR, Megarbane A, Urtizberea JA, Hernandez DG, Foley AR, Arepalli S, Pandraud A, Simon-Sanchez J, Glayton P, Reilly MM, Muntoni F, Abramzon Y, Houlden H, Singleton AB.   Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease.  Brain 2012 Sep;135(Pt 9):2875-82. Epub 2012 Jun 26.

Nabokina SM, Subramanian VS, Said HM. Effect of clinical mutations on functionality of the human riboflavin transporter-2 (hRFT-2).Mol Genet Metab. 2012 Apr;105(4):652-7. Epub 2012 Jan 5.

Spagnoli C, De Sousa C. Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease - treatable motor neuron diseases of childhood.Dev Med Child Neurol. 2012 Apr;54(4):292-3. doi: 10.1111/ j.1469-8749. 2011.04179.x  Epub 2011 Dec 29.

Anand G, Hasan N, Jayapal S, Huma Z, Ali T, Hull J, Blair E, McShane T, Jayawant S. Early use of high-dose riboflavin in a case of Brown-Vialetto-Van Laere syndrome. Dev Med Child Neurol. 2012 Feb;54(2):187-9. doi: 10.1111/j.1469-8749.2011.04142.x. Epub 2011 Nov 18.

Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR. 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. 2011 Feb;34(1):159-64. Epub 2010 Nov 26.

da Silva-Júnior FP, Moura Rde D, Rosemberg S, Marchiori PE, Castro LH. Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: a case report.J Neurol Sci. 2011 Jan 15;300(1-2):155-6. Epub 2010 Nov 5.

Sinnathuray AR, Watson DR, Fruhstorfer B, Olarte JR, Toner JG. Cochlear Implantation in Brown-Vialetto-Van-Laere syndrome.J Laryngol Otol. 2011 Mar;125(3):314-7. Epub 2010 Oct 19.

Johnson JO, Gibbs JR, Van Maldergem L, Houlden H, Singleton AB. Exome sequencing in Brown-Vialetto-van Laere syndrome.Am J Hum Genet.

2010 Oct 8;87(4):567-9; author reply 569- 70.

Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin J, Raymond FL, Childs A, Sheridan E, Edwards S, Josifova DJ. Brown-Vialetto-Van Laere Syndrome, a Ponto-Bulbar Palsy with Deafness, Is Caused by Mutations in C20orf54. The American Journal of Human Genetics. March 4, 2010.

2009 and Preceding:
Dakhil FO, Bensreiti SM, Zew MH. Pontobulbar palsy and sensorineural deafness (Brown-Vialetto-van Laere syndrome): the first case from Libya. Amyotrophic Lateral Sclerosis. 2009. [Epub ahead of print]

Fell D. Anesthesia in Brown-Vialetto-Van Laere syndrome. Paediatr Anaesth. 2009 Nov;19(11):1130-1.

Nickols HH, Qualtieri J, Wills ML, Kinney HC, Becher, MW. The neuropathology of Brown-Vialetto-Van Laere Syndrome (BVVL): a detailed case report. Journal of Neuropathology and Experimental Neurology 2009, May 68;5:552-593.

Sathasivam S. Brown-Vialetto-Van Laere syndrome. Orphanet Journal of Rare Diseases 2008, April 17;3:9.  (As of April 2008, the most comprehensive review of BVVL).

Malheiros JA, Camargos ST, de Oliveira JT, Cardoso FEC. A brazilian family with Brown-Vialetto-Van Laere syndrome with autosomal recessive inheritance. Arq Neuropsiquiatr. 2007;65:32–35.

Koul R, Jain R, Chacko A, Alfutaisi A, Hashim J, Chacko J. Pontobulbar palsy and neurosensory deafness (Brown-Vialetto-Van Laere syndrome) with hyperintense brainstem nuclei on magnetic resonance imaging: new finding in three siblings. J Child Neurol. 2006;21:523–525.

Dipti S, Childs A-M, Livingston JH, Aggarwal AK, Miller M, Williams C, Crow YJ. Brown-Vialetto-Van Laere syndrome: variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease. Brain Dev. 2005;27:443–446.

Prabhu HV, Brown MJK. Brown-Vialetto-Van Laere syndrome: a rare syndrome in otology – case report and literature review. J Laryngol Otol. 2005;119:470–472.

Nemoto H, Konno S, Nomoto N, Wakata N, Kurihara T. A case of Brown-Vialetto-van Laere (BVVL) syndrome in Japan. Clin Neurol. 2005;45:357–361.

Aydin, ÖF.;Özcelikel, D.;Senbil, N.; Gürer, YKY. Brown-Vialetto-van Laere syndrome; the first turkish case. Acta Neurol Belg. 2004;104:111–113.

RamachandranNair R, Parameswaran M, Girija AS. Vialetto-Van Laere syndrome in two sisters born to consanguineous parents. Pediatr Neurol. 2004;30:354–355.

Introini S, Sasso GM, Moioli G, Morandini WL. Un caso clinico Sindrome di Brown-Vialetto-Van Laere. Minerva Anestesiol. 2003;69:75–79.

Voudris KA, Skardoutsou A, Vagiakou A. Infantile progressive bulbar palsy with deafness. Brain Dev. 2002;24:732–735.

Mégarbané A, Desguerres I, Rizkallah E, Delague V, Nabbout R, Barois A, Urtizberea A. Brown-Vialetto-Van Laere syndrome in a large inbred Lebanese family: confirmation of autosomal recessive inheritance? Am J Med Genet. 2000;92:117–121.

Sathasivam S, O'Sullivan S, Nicolson A, Tilley PJ, Shaw PJ. Brown-Vialetto-Van Laere syndrome: case report and literature review. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:277–281.

Orrell RW, Habgood JJ, De Belleroche JS, Lane RJM. The relationship of spinal muscular atrophy to motor neuron disease: investigation of SMN and NAIP gene deletions in sporadic and familial ALS. J Neurol Sci. 1997;145:55–61.

Puri V, Rohtagi A, Parihar PS. Ponto-bulbar palsy with deafness (Vialetto-Van Laere syndrome). Indian Pediatr. 1996;33:140–142.

Davenport RJ, Mumford CJ. The Brown-Vialetto-Van Laere syndrome: a case report and literature review. Eur J Neurol. 1994;1:51–54.

Francis DA, Ponsford JR, Wiles CM, Thomas PK, Duchen LW. Case report. Brown-Vialetto-Van Laere syndrome. Neuropathol Appl Neurobiol. 1993;19:91–94.

Abarbanel JM, Ashby P, Marquez-Julio A, Chapman KR. Bulbo-pontine paralysis with deafness: the Vialetto-Van Laere syndrome. Can J Neurol Sci. 1991;18:349–351.

Hawkins SA, Nevin NC, Harding AE. Pontobulbar palsy and neurosensory deafness (Brown-Vialetto-Van Laere syndrome) with possible autosomal dominant inheritance. J Med Genet. 1990;27:176–179.

Rosemberg S, Carmen LP, Arita F, Campos C, de Castro NP Jr. Progressive bulbar paralysis of childhood (Fazio-Londe disease) with deafness. Eur Neurol. 1982;21:84–89.

Gallai V, Hockaday JM, Hughes JT, Lane DJ, Oppenheimer DR, Rushworth G. Ponto-bulbar palsy with deafness (Brown-Vialetto-Van Laere syndrome). J Neurol Sci. 1981;50:259–275.

Brucher JM, Dom R, Lombaert A, Carton H. Progressive pontobulbar palsy with deafness. Clinical and pathological study of two cases. Arch Neurol. 1981;38:186–190.

Serratrice G, Gastaut JL. Amyotrophies dégénératives et lesions du neurone moteur (á propos de 32 observations). Marseille Méd. 1972;109:821–840.

Boudin G, Pépin B, Vernant JC, Gautier B, Gouérou H. Cas familial de paralysie bulbo-pontine chronique progressive avec surdité Rev Neurol. 1971;124:90–92.

Orrell RW, Habgood JJ, De Belleroche JS, Lane RJM. The relationship of spinal muscular atrophy to motor neuron disease: investigation of SMN and NAIP gene deletions in sporadic and familial ALS. J Neurol Sci. 1997;145:55–61.

The original publications and authors for which the disease is named:

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. 

Van Laere J. Over een nieuw geval van chronische bulbopontine paralysis met doofheid. Verh Vlaam Akad Geneesk Belg. 1967;30:228–308.

Van Laere J. Un nouveau cas de paralysie bulbo-pontine chronique progressive avec surdité Rev Neurol. 1977;133:119–124.

BVVL Research Highlights

BVVL International was founded as an aid to anyone interested in uncovering the mystery of Brown-Vialetto-Van Laere syndrome and ultimately,
in finding a cure.


We are pleased to share the work done by Dr. Bosch and colleagues in the Netherlands in the Division of Metabolic Disorders at University Hospital of Amsterdam (See  initial article and contact information below).  Around the same time that the first gene was documented (2010), Dr. Bosch's team was working on high dose riboflavin (Vitamin B2) supplementation in patients who had BVVL and a similar disease, Fazio Londe. 

In October 2012, Dr. Bosch's team published a review on the literature of BVVL and Fazio Londe syndromes, with recommendations for treatment. The following link has open access with a provisional PDF; however, you may email us directly for a copy from our library:

Please visit our Research Highlights page for ongoing reports of riboflavin supplementation in the literature.


When this web site was founded in 2008, a large collaborative effort among physicians and researchers in the United Kingdom and the United States were studying tissue from at least ten families affected by the disease in order to learn which genetic mechanism(s) is responsible for Brown-Vialetto-Van Laere. March 4, 2010, brought forth the first publication of a BVVL genetic finding, on C20orf54 (See below). Since that time, other genes have been named in the BVVL and FL disease processes. However, more samples from affected families are needed in order to expand this research, as well as ongoing research towards a cure.

Contact Dr. Henry Houlden of the MRC centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London for more information: