Monogenic hearing loss

Gene: SLC52A3

Green List (high evidence)

A 'treatable' tag was added as high-dose riboflavin supplementation early on is effective in stopping disease progression and possibly lifesaving (https://www.ncbi.nlm.nih.gov/books/NBK299312/)

Created: 22 May 2026, 9:16 a.m. | Last Modified: 22 May 2026, 9:16 a.m.

Panel Version: 6.12

Comment on mode of inheritance: There are more than 3 unrelated patients with both monoallelic and biallelic variants in SLC52A3 and Brown-Vialetto-Van Laere syndrome. Both modes of inheritance result in the same phenotype of hearing loss and ponto-bulbar palsy / bilateral vestibular neuropathy. Hence, the mode of inheritance for Monogenic hearing loss should be updated from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 22 May 2026, 9:07 a.m. | Last Modified: 22 May 2026, 9:07 a.m.

Panel Version: 6.10

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Variant in only one allele was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported 6 patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele. Sensorineural hearing loss was present in 5/6 patients, and the presenting symptom in 3 of the heterozygous cases.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient (Case 3) was identified with a heterozygous variant and progressive hearing loss, bilateral steppage gait and a cranial nerves impairment, diagnosed with bilateral vestibular neuropathy.
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PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency: sensorineural hearing loss, progressive bulbar and predominantly distal upper and lower extremity weakness. Symptoms started with right eyelid ptosis and sensory changes on the left face. Over the next three months, she developed bilateral hand tremors and distal weakness followed by progressive bifacial weakness, dysarthria, and dysphagia. She was identified with a novel heterozygous variant SLC52A3 p.Tyr324Cys, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant - reduced penetrance for the monoallelic state. Her condition improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.

Created: 22 May 2026, 9:02 a.m. | Last Modified: 22 May 2026, 9:02 a.m.

Panel Version: 6.10

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome 1, OMIM:211530; Brown-Vialetto-van Laere syndrome 1, MONDO:0024537; ?Fazio-Londe disease, OMIM:211500; riboflavin transporter deficiency, MONDO:0008891

Publications

• 22718020
• 29053833
• 34384672
• 38469093
• 40539137

Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.

Created: 20 Oct 2020, 8:03 a.m. | Last Modified: 20 Oct 2020, 8:03 a.m.

Panel Version: 2.96

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.

Panel Version: 2.221

Comment on list classification: More than 3 cases reported with variants in SLC52A3 in patients Brown-Vialetto-van Laere syndrome. Sensorineural deafness is a feature of this syndrome and often presents first.

Created: 11 May 2020, 11:34 a.m. | Last Modified: 11 May 2020, 11:34 a.m.

Panel Version: 2.11

Associated with Brown-Vialetto-Van Laere syndrome 1 #211530 (AR) in OMIM, a form of progressive bulbar palsy with sensorineural deafness.

Multiple cases of variants in this gene have been found in patients with Brown-Vialetto-Van Laere syndrome 1:

PMID: 20206331 Green et al 2010 - identified homozygous or compound heterozygous variants in C20orf54 (SLC52A3) in individuals with Brown-Vialetto-Van Laere syndrome from 7 families of European, Pakistani and Arabic ancestry. Nonsense and missense variants were found. Used homozgyosity mapping in the first family and then candidate gene analysis. They also report that 58 cases have been documented in the literature, with the age at onset ranged from infancy to early in the third decade, with the majority presenting in the second decade. Hearing loss preceded the onset of neurological signs in most cases. C20ORF54 is thought to play a role in riboflavin transport.

PMID: 20920669 Johnson et al 2010 - performed exome sequencing in patients with Brown-Vialetto-van Laere syndrome. In one patient in common with Green et al 2010 they found compound heterozygous variants in C20orf54 (patient 2008-410) rather than the homozygous variant Green et al reported (case 4). The results were confirmed by Sanger sequence and the parents were found to each have 1 heterozygous variant. They also report an additional family (DZ) from Eastern Turkey with a homozygous variant in affected individuals.

Created: 11 May 2020, 11:32 a.m. | Last Modified: 11 May 2020, 11:32 a.m.

Panel Version: 2.10

Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust). Sensorineural deafness is the presenting feature in cases presenting after infancy with other neurology a year or 2 later – treatment with Riboflavin can be effective.
Sources: Expert list

Created: 11 May 2020, 10:02 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal