BVVLS2
MCID: BRW008
MIFTS: 37

Brown-Vialetto-Van Laere Syndrome 2 (BVVLS2)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Brown-Vialetto-Van Laere Syndrome 2

MalaCards integrated aliases for Brown-Vialetto-Van Laere Syndrome 2:

Name: Brown-Vialetto-Van Laere Syndrome 2 57 12 20 72 29 13 6 70
Bvvls2 57 72
Rfvt3-Related Riboflavin Transporter Deficiency 58
Brown-Vialetto-Van Laere Syndrome, Type 2 39
Riboflavin Transporter Deficiency 3 58
Rtd3 58

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
early death from respiratory failure may occur
onset in first few years of life
some patients show significant clinical improvement with riboflavin supplementation


HPO:

31
brown-vialetto-van laere syndrome 2:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare otorhinolaryngological diseases
Developmental anomalies during embryogenesis


Summaries for Brown-Vialetto-Van Laere Syndrome 2

OMIM® : 57 Brown-Vialetto-Van Laere syndrome-2 is an autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency. Some patients may lose independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation (summary by Johnson et al., 2012; Foley et al., 2014). For discussion of genetic heterogeneity of Brown-Vialetto-Van Laere syndrome, see BVVLS1 (211530). (614707) (Updated 20-May-2021)

MalaCards based summary : Brown-Vialetto-Van Laere Syndrome 2, also known as bvvls2, is related to madras motor neuron disease and motor neuron disease, and has symptoms including ataxia, clumsiness and facial paresis. An important gene associated with Brown-Vialetto-Van Laere Syndrome 2 is SLC52A2 (Solute Carrier Family 52 Member 2), and among its related pathways/superpathways is Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include eye and tongue, and related phenotypes are nystagmus and dysphagia

Disease Ontology : 12 A Brown-Vialetto-Van Laere syndrome that is characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency and that has material basis in homozygous or compound heterozygous mutation in the SLC52A2 gene on chromosome 8q24.

UniProtKB/Swiss-Prot : 72 Brown-Vialetto-Van Laere syndrome 2: An autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting resulting in respiratory insufficiency and loss of independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation.

Related Diseases for Brown-Vialetto-Van Laere Syndrome 2

Graphical network of the top 20 diseases related to Brown-Vialetto-Van Laere Syndrome 2:



Diseases related to Brown-Vialetto-Van Laere Syndrome 2

Symptoms & Phenotypes for Brown-Vialetto-Van Laere Syndrome 2

Human phenotypes related to Brown-Vialetto-Van Laere Syndrome 2:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 nystagmus 31 occasional (7.5%) HP:0000639
2 dysphagia 31 occasional (7.5%) HP:0002015
3 optic atrophy 31 occasional (7.5%) HP:0000648
4 kyphoscoliosis 31 occasional (7.5%) HP:0002751
5 organic aciduria 31 occasional (7.5%) HP:0001992
6 aggressive behavior 31 occasional (7.5%) HP:0000718
7 visual loss 31 occasional (7.5%) HP:0000572
8 ataxia 31 HP:0001251
9 facial palsy 31 HP:0010628
10 respiratory insufficiency 31 HP:0002093
11 sensorineural hearing impairment 31 HP:0000407
12 areflexia 31 HP:0001284
13 split hand 31 HP:0001171
14 clumsiness 31 HP:0002312
15 limb muscle weakness 31 HP:0003690
16 generalized hypotonia 31 HP:0001290
17 hypokinesia 31 HP:0002375
18 generalized amyotrophy 31 HP:0003700
19 sensorimotor neuropathy 31 HP:0007141
20 bulbar palsy 31 HP:0001283
21 neck muscle weakness 31 HP:0000467
22 tongue fasciculations 31 HP:0001308

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
nystagmus
optic atrophy
visual loss
absent pupillary reflex

Respiratory:
respiratory insufficiency
sleep hypoventilation (rare)

Laboratory Abnormalities:
organic aciduria
abnormal acylcarnitine profiles

Head And Neck Mouth:
tongue fasciculations

Head And Neck Face:
facial muscle weakness

Skeletal Spine:
scoliosis (in some patients)
kyphoscoliosis (in some patients)

Abdomen Gastrointestinal:
dysphagia (in some patients)

Neurologic Central Nervous System:
ataxia
clumsiness
bulbar palsy
loss of independent ambulation
cranial nerve palsies
more
Neurologic Peripheral Nervous System:
areflexia
axonal sensorimotor neuropathy
sural nerve biopsy shows loss of large myelinated fibers

Head And Neck Neck:
neck muscle weakness

Muscle Soft Tissue:
hypotonia
fibrillations
neurogenic changes seen on emg
muscle weakness, proximal, distal, and axial, severe
upper limb muscle weakness may be more severe than lower limb weakness
more
Head And Neck Ears:
hearing loss, sensorineural
absent brainstem auditory-evoked responses

Skeletal Hands:
claw hands

Neurologic Behavioral Psychiatric Manifestations:
aggressive behavior (in some patients)

Clinical features from OMIM®:

614707 (Updated 20-May-2021)

UMLS symptoms related to Brown-Vialetto-Van Laere Syndrome 2:


ataxia; clumsiness; facial paresis; unspecified visual loss

Drugs & Therapeutics for Brown-Vialetto-Van Laere Syndrome 2

Search Clinical Trials , NIH Clinical Center for Brown-Vialetto-Van Laere Syndrome 2

Genetic Tests for Brown-Vialetto-Van Laere Syndrome 2

Genetic tests related to Brown-Vialetto-Van Laere Syndrome 2:

# Genetic test Affiliating Genes
1 Brown-Vialetto-Van Laere Syndrome 2 29 SLC52A2

Anatomical Context for Brown-Vialetto-Van Laere Syndrome 2

MalaCards organs/tissues related to Brown-Vialetto-Van Laere Syndrome 2:

40
Eye, Tongue

Publications for Brown-Vialetto-Van Laere Syndrome 2

Articles related to Brown-Vialetto-Van Laere Syndrome 2:

(show all 15)
# Title Authors PMID Year
1
Oral therapy for riboflavin transporter deficiency - What is the regimen of choice? 57 6
30343981 2019
2
Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. 57 6
24253200 2014
3
Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations. 6 57
23243084 2013
4
Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome. 57 6
22864630 2012
5
Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. 6 57
22740598 2012
6
Brown-Vialetto-Van Laere syndrome in a large inbred Lebanese family: confirmation of autosomal recessive inheritance? 57 6
10797435 2000
7
Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition. 6 61
27148561 2015
8
Clinical, pathological and functional characterization of riboflavin-responsive neuropathy. 6
29053833 2017
9
Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2). 6
26669662 2016
10
Large-scale whole-genome sequencing of the Icelandic population. 6
25807286 2015
11
Identification of residues/sequences in the human riboflavin transporter-2 that is important for function and cell biology. 6
25798182 2015
12
Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood. 6
24616084 2014
13
Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. 6
25133958 2014
14
Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study. 6
22824638 2012
15
Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing. 61
27148562 2015

Variations for Brown-Vialetto-Van Laere Syndrome 2

ClinVar genetic disease variations for Brown-Vialetto-Van Laere Syndrome 2:

6 (show top 50) (show all 188)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC52A2 NM_001363118.2(SLC52A2):c.368T>C (p.Leu123Pro) SNV Pathogenic 39576 rs397514538 GRCh37: 8:145583520-145583520
GRCh38: 8:144359860-144359860
2 SLC52A2 NM_001363118.2(SLC52A2):c.1255G>A (p.Gly419Ser) SNV Pathogenic 40232 rs397514658 GRCh37: 8:145584592-145584592
GRCh38: 8:144360932-144360932
3 SLC52A2 NM_001363118.2(SLC52A2):c.851C>A (p.Ala284Asp) SNV Pathogenic 96702 rs398123067 GRCh37: 8:145584003-145584003
GRCh38: 8:144360343-144360343
4 SLC52A2 NM_001363118.2(SLC52A2):c.914A>G (p.Tyr305Cys) SNV Pathogenic 96703 rs398123068 GRCh37: 8:145584066-145584066
GRCh38: 8:144360406-144360406
5 SLC52A2 NM_001363118.2(SLC52A2):c.92G>C (p.Trp31Ser) SNV Pathogenic 210037 rs797045199 GRCh37: 8:145583045-145583045
GRCh38: 8:144359385-144359385
6 SLC52A2 NM_001363118.2(SLC52A2):c.700C>T (p.Gln234Ter) SNV Pathogenic 210039 rs797045200 GRCh37: 8:145583852-145583852
GRCh38: 8:144360192-144360192
7 SLC52A2 NM_001363118.2(SLC52A2):c.865C>T (p.Leu289=) SNV Pathogenic 210040 rs797045201 GRCh37: 8:145584017-145584017
GRCh38: 8:144360357-144360357
8 SLC52A2 NM_001363118.2(SLC52A2):c.551del (p.Pro184fs) Deletion Pathogenic 473205 rs1554854044 GRCh37: 8:145583698-145583698
GRCh38: 8:144360038-144360038
9 SLC52A2 NM_001363118.2(SLC52A2):c.116_130+83del Deletion Pathogenic 576124 rs1564653965 GRCh37: 8:145583037-145583134
GRCh38: 8:144359377-144359474
10 SLC52A2 NM_001363118.2(SLC52A2):c.751C>T (p.Gln251Ter) SNV Pathogenic 660959 rs1312209529 GRCh37: 8:145583903-145583903
GRCh38: 8:144360243-144360243
11 SLC52A2 NM_001363118.2(SLC52A2):c.402CTT[1] (p.Phe135del) Microsatellite Pathogenic 929820 GRCh37: 8:145583554-145583556
GRCh38: 8:144359894-144359896
12 SLC52A2 NM_001363118.2(SLC52A2):c.916G>A (p.Gly306Arg) SNV Pathogenic 35470 rs398124641 GRCh37: 8:145584068-145584068
GRCh38: 8:144360408-144360408
13 SLC52A2 NM_001363118.2(SLC52A2):c.1016T>C (p.Leu339Pro) SNV Pathogenic 39577 rs148234606 GRCh37: 8:145584264-145584264
GRCh38: 8:144360604-144360604
14 SLC52A2 NM_001363118.2(SLC52A2):c.155C>T (p.Ser52Phe) SNV Pathogenic 40231 rs397514657 GRCh37: 8:145583307-145583307
GRCh38: 8:144359647-144359647
15 SLC52A2 NM_001363118.2(SLC52A2):c.808C>T (p.Gln270Ter) SNV Pathogenic 188051 rs375088539 GRCh37: 8:145583960-145583960
GRCh38: 8:144360300-144360300
16 SLC52A2 NC_000008.11:g.(?_144358571)_(144361296_?)del Deletion Pathogenic 830619 GRCh37: 8:145582231-145584956
GRCh38:
17 SLC52A2 NM_001363118.2(SLC52A2):c.149dup (p.Tyr50Ter) Duplication Pathogenic 419108 rs782095095 GRCh37: 8:145583300-145583301
GRCh38: 8:144359640-144359641
18 SLC52A2 NM_001363118.2(SLC52A2):c.968T>C (p.Leu323Pro) SNV Likely pathogenic 979035 GRCh37: 8:145584120-145584120
GRCh38: 8:144360460-144360460
19 SLC52A2 NM_001363118.2(SLC52A2):c.935T>C (p.Leu312Pro) SNV Likely pathogenic 210041 rs754320812 GRCh37: 8:145584087-145584087
GRCh38: 8:144360427-144360427
20 SLC52A2 NM_001363118.2(SLC52A2):c.131-1G>C SNV Likely pathogenic 580165 rs782305211 GRCh37: 8:145583282-145583282
GRCh38: 8:144359622-144359622
21 SLC52A2 NM_001363118.2(SLC52A2):c.505C>T (p.Arg169Cys) SNV Conflicting interpretations of pathogenicity 212207 rs782345472 GRCh37: 8:145583657-145583657
GRCh38: 8:144359997-144359997
22 SLC52A2 NM_001363118.2(SLC52A2):c.383C>T (p.Ser128Leu) SNV Conflicting interpretations of pathogenicity 210038 rs374071862 GRCh37: 8:145583535-145583535
GRCh38: 8:144359875-144359875
23 SLC52A2 NM_001363118.2(SLC52A2):c.1088C>T (p.Pro363Leu) SNV Conflicting interpretations of pathogenicity 210042 rs797045202 GRCh37: 8:145584336-145584336
GRCh38: 8:144360676-144360676
24 SLC52A2 NM_001363118.2(SLC52A2):c.-110-1G>A SNV Uncertain significance 549670 rs1554853682 GRCh37: 8:145582843-145582843
GRCh38: 8:144359183-144359183
25 SLC52A2 NM_001363118.2(SLC52A2):c.424C>T (p.Arg142Cys) SNV Uncertain significance 569976 rs1016614259 GRCh37: 8:145583576-145583576
GRCh38: 8:144359916-144359916
26 SLC52A2 NM_001363118.2(SLC52A2):c.1153G>A (p.Val385Met) SNV Uncertain significance 1037886 GRCh37: 8:145584490-145584490
GRCh38: 8:144360830-144360830
27 SLC52A2 NM_001363118.2(SLC52A2):c.418C>T (p.Pro140Ser) SNV Uncertain significance 1038156 GRCh37: 8:145583570-145583570
GRCh38: 8:144359910-144359910
28 SLC52A2 NM_001363118.2(SLC52A2):c.308C>T (p.Ala103Val) SNV Uncertain significance 1041637 GRCh37: 8:145583460-145583460
GRCh38: 8:144359800-144359800
29 SLC52A2 NM_001363118.2(SLC52A2):c.777C>T (p.Gly259=) SNV Uncertain significance 1042426 GRCh37: 8:145583929-145583929
GRCh38: 8:144360269-144360269
30 SLC52A2 NM_001363118.2(SLC52A2):c.736G>C (p.Glu246Gln) SNV Uncertain significance 246565 rs879254314 GRCh37: 8:145583888-145583888
GRCh38: 8:144360228-144360228
31 SLC52A2 NM_001363118.2(SLC52A2):c.533A>G (p.Asn178Ser) SNV Uncertain significance 1047068 GRCh37: 8:145583685-145583685
GRCh38: 8:144360025-144360025
32 SLC52A2 NM_001363118.2(SLC52A2):c.145T>C (p.Ser49Pro) SNV Uncertain significance 1047525 GRCh37: 8:145583297-145583297
GRCh38: 8:144359637-144359637
33 SLC52A2 NM_001363118.2(SLC52A2):c.425G>A (p.Arg142His) SNV Uncertain significance 540427 rs560681538 GRCh37: 8:145583577-145583577
GRCh38: 8:144359917-144359917
34 SLC52A2 NM_001363118.2(SLC52A2):c.1106C>T (p.Ser369Leu) SNV Uncertain significance 540434 rs138160033 GRCh37: 8:145584354-145584354
GRCh38: 8:144360694-144360694
35 SLC52A2 NM_001363118.2(SLC52A2):c.806A>G (p.Tyr269Cys) SNV Uncertain significance 246504 rs372057075 GRCh37: 8:145583958-145583958
GRCh38: 8:144360298-144360298
36 SLC52A2 NM_001363118.2(SLC52A2):c.1227C>T (p.Gly409=) SNV Uncertain significance 641307 rs147518188 GRCh37: 8:145584564-145584564
GRCh38: 8:144360904-144360904
37 SLC52A2 NM_001363118.2(SLC52A2):c.13A>T (p.Thr5Ser) SNV Uncertain significance 653493 rs781993535 GRCh37: 8:145582966-145582966
GRCh38: 8:144359306-144359306
38 SLC52A2 NM_001363118.2(SLC52A2):c.920G>A (p.Arg307His) SNV Uncertain significance 665799 rs143091206 GRCh37: 8:145584072-145584072
GRCh38: 8:144360412-144360412
39 SLC52A2 NM_001363118.2(SLC52A2):c.275C>T (p.Thr92Ile) SNV Uncertain significance 840383 GRCh37: 8:145583427-145583427
GRCh38: 8:144359767-144359767
40 SLC52A2 NM_001363118.2(SLC52A2):c.625G>A (p.Ala209Thr) SNV Uncertain significance 845792 GRCh37: 8:145583777-145583777
GRCh38: 8:144360117-144360117
41 SLC52A2 NM_001363118.2(SLC52A2):c.22C>T (p.Arg8Cys) SNV Uncertain significance 846798 GRCh37: 8:145582975-145582975
GRCh38: 8:144359315-144359315
42 SLC52A2 NM_001363118.2(SLC52A2):c.63G>T (p.Met21Ile) SNV Uncertain significance 473206 rs764635442 GRCh37: 8:145583016-145583016
GRCh38: 8:144359356-144359356
43 SLC52A2 NM_001363118.2(SLC52A2):c.1277C>T (p.Pro426Leu) SNV Uncertain significance 540436 rs201673476 GRCh37: 8:145584614-145584614
GRCh38: 8:144360954-144360954
44 SLC52A2 NM_001363118.2(SLC52A2):c.1178C>T (p.Ala393Val) SNV Uncertain significance 540437 rs782396304 GRCh37: 8:145584515-145584515
GRCh38: 8:144360855-144360855
45 SLC52A2 NM_001363118.2(SLC52A2):c.679G>A (p.Gly227Arg) SNV Uncertain significance 568089 rs781816242 GRCh37: 8:145583831-145583831
GRCh38: 8:144360171-144360171
46 SLC52A2 NM_001363118.2(SLC52A2):c.605C>T (p.Ala202Val) SNV Uncertain significance 570905 rs1166880307 GRCh37: 8:145583757-145583757
GRCh38: 8:144360097-144360097
47 SLC52A2 NM_001363118.2(SLC52A2):c.143C>T (p.Pro48Leu) SNV Uncertain significance 575643 rs1554853840 GRCh37: 8:145583295-145583295
GRCh38: 8:144359635-144359635
48 SLC52A2 NM_001363118.2(SLC52A2):c.602C>A (p.Thr201Asn) SNV Uncertain significance 659402 rs552024614 GRCh37: 8:145583754-145583754
GRCh38: 8:144360094-144360094
49 SLC52A2 NM_001363118.2(SLC52A2):c.656C>T (p.Pro219Leu) SNV Uncertain significance 837415 GRCh37: 8:145583808-145583808
GRCh38: 8:144360148-144360148
50 SLC52A2 NM_001363118.2(SLC52A2):c.556G>A (p.Asp186Asn) SNV Uncertain significance 838343 GRCh37: 8:145583708-145583708
GRCh38: 8:144360048-144360048

UniProtKB/Swiss-Prot genetic disease variations for Brown-Vialetto-Van Laere Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 SLC52A2 p.Gly306Arg VAR_068694 rs398124641
2 SLC52A2 p.Trp31Ser VAR_077433 rs797045199
3 SLC52A2 p.Ser52Phe VAR_077434 rs397514657
4 SLC52A2 p.Leu123Pro VAR_077435 rs397514538
5 SLC52A2 p.Pro141Thr VAR_077436 rs377740960
6 SLC52A2 p.Ala284Asp VAR_077437 rs398123067
7 SLC52A2 p.Tyr305Cys VAR_077438 rs398123068
8 SLC52A2 p.Leu312Pro VAR_077439 rs754320812
9 SLC52A2 p.Leu339Pro VAR_077440 rs148234606
10 SLC52A2 p.Gly419Ser VAR_077441 rs397514658

Expression for Brown-Vialetto-Van Laere Syndrome 2

Search GEO for disease gene expression data for Brown-Vialetto-Van Laere Syndrome 2.

Pathways for Brown-Vialetto-Van Laere Syndrome 2

GO Terms for Brown-Vialetto-Van Laere Syndrome 2

Biological processes related to Brown-Vialetto-Van Laere Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 riboflavin metabolic process GO:0006771 8.96 SLC52A3 SLC52A2
2 riboflavin transport GO:0032218 8.62 SLC52A3 SLC52A2

Molecular functions related to Brown-Vialetto-Van Laere Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 riboflavin transmembrane transporter activity GO:0032217 8.62 SLC52A3 SLC52A2

Sources for Brown-Vialetto-Van Laere Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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