The Invitae Riboflavin Transporter Deficiency Neuronopathy Panel analyzes two genes associated with riboflavin transporter deficiency, which is also known as Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease. These genes were curated based on the available evidence to date to provide a comprehensive test for this condition.
Individuals with clinical signs and symptoms of riboflavin transporter deficiency may benefit from diagnostic genetic testing to confirm the diagnosis, guide clinical treatment and inform recurrence risk within a family.
Riboflavin transporter deficiency may also have nonspecific or overlapping features with other neurological disorders, in which case clinicians may consider Invitae’s Comprehensive Neuropathy panel, which includes genes associated with Charcot-Marie-Tooth disease, distal hereditary motor neuropathy, hereditary sensory and autonomic neuropathy and hereditary spastic paraplegia.
Riboflavin transporter deficiency neuronopathy is a neurodegenerative disorder characterized by progressive axonal sensorimotor neuropathy. Clinical features of this disorder include bulbar palsy (facial weakness, drooping eyelids, difficulty speaking and swallowing), weakness and distal muscle atrophy in the limbs (typically more severe in the upper than lower limbs), respiratory distress due to diaphragmatic weakness, and gait ataxia. Sensorineural hearing loss occurs in many individuals and may be the presenting symptom. Historically, the clinical subtype of riboflavin transporter deficiency neuronopathy that includes hearing loss has been called Brown-Vialetto-Van Laere syndrome, and the clinical subtype that does not include hearing loss has been called Fazio-Londe disease. Onset of symptoms typically occurs in early childhood;however, genetically confirmed early-adult onset cases have been reported. Since the discovery of the underlying molecular defect in this disorder, high-dose riboflavin supplementation has been reported to be an effective treatment.
SLC52A2 and SLC52A3 are the only known causes of riboflavin transporter deficiency neuronopathy. However, due to the rareness of this disorder, the clinical sensitivity of this panel has not been confirmed.
Riboflavin transporter deficiency neuronopathy is inherited in an autosomal recessive manner.
In families with genetically confirmed riboflavin transporter deficiency neuronopathy penetrance is high, but the number of families reported in the literature is low due to the rareness of this disorder.
Riboflavin transporter deficiency neuronopathy is a rare disorder and has a prevalence of less than 1 in 1,000,000.
The clinical presentation of riboflavin transporter deficiency neuronopathy is variable, and may be difficult to distinguish clinically from other neurological disorders. Genetic testing may confirm a suspected diagnosis or rule out other disorders with similar symptoms. A genetic diagnosis may also help guide treatment and inform recurrence risk.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|