Paediatric motor neuronopathies

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: 3.16

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 Paediatric motor neuronopathies should be updated from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 22 May 2026, 9:11 a.m. | Last Modified: 22 May 2026, 9:11 a.m.

Panel Version: 3.14

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, 9:10 a.m. | Last Modified: 22 May 2026, 9:10 a.m.

Panel Version: 3.14

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

Green List (high evidence)

many families reported
well characterised phenotype

Created: 2 Mar 2017, 4:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome; infantile motor neuronopathy; deafness; respiratory insufficiency

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Many reported individuals with mutations in this gene. Diagnostic test offered on UKGTN

Created: 2 Nov 2016, 11:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome 1, 211530

Publications

• 20206331
• 20920669