Understanding SLC6A6 Variants in Early-Onset Retinopathy

A multicenter cohort study identifies biallelic SLC6A6 variants as the cause of a childhood-onset, rod-predominant retinal dystrophy—clarifying genotype–phenotype correlations and expanding the diagnostic gene-panel for early nyctalopia and macular atrophy.

Symptom onset clustered in early childhood, with nyctalopia frequently the initial complaint. Progression varied, but most patients reported worsening night vision before central retinal changes emerged.

Macular atrophy was common on examination; visual acuity at last follow-up ranged from moderate impairment to hand motions. Electroretinography typically showed reduced scotopic responses consistent with rod dysfunction, often accompanied by cone dysfunction.

SLC6A6 encodes a sodium- and chloride-dependent taurine transporter expressed in retinal tissue. Impaired taurine transport is implicated as the mechanistic link to photoreceptor dysfunction and progressive retinal degeneration.

When evaluating childhood-onset retinal dystrophy with early nyctalopia, attenuated scotopic ERG responses, or unexplained macular atrophy, clinicians may include SLC6A6 on gene-panel testing and pursue genetic counseling given autosomal recessive inheritance and a 25% recurrence risk.

Key Takeaways:

• Biallelic SLC6A6 variants cause a measurable, childhood-onset rod-predominant retinal dystrophy with acuity loss and ERG abnormalities—reshaping the genetic differential and informing panel design.
• Children presenting with early nyctalopia, macular atrophy, and reduced scotopic ERG responses are most commonly affected; affected families show autosomal recessive inheritance with implications for carrier testing and reproductive counseling.
• Diagnostic workflows should prioritize broad sequencing for compatible phenotypes and consider enrollment in mechanistic studies of taurine biology—early molecular diagnosis refines prognosis, surveillance, and eligibility for emerging therapeutic research.