NRL – Enhanced S-Cone Syndrome

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal dystrophy most commonly caused by biallelic NR2E3 variants but also rarely by NRL mutations. In a series of three Moroccan patients from two unrelated consanguineous families, autosomal recessive NRL variants were identified in individuals presenting with early-onset nyctalopia (HP:0000662) and reduced visual acuity (HP:0007663) alongside clumped pigmentary retinal degeneration and characteristic electroretinographic findings (PMID:29385733; PMID:37719593). These clinical features include absent scotopic responses at low stimulus strengths, reduced responses at high intensities, and relatively enhanced S-cone amplitudes, confirming functional overlap with NR2E3-associated ESCS.

Genetic analysis revealed one patient homozygous for the missense variant c.508C>A (p.Arg170Ser) and two siblings compound heterozygous for c.508C>A (p.Arg170Ser) in trans with a one-base deletion c.654del (p.Cys219ValfsTer4) (PMID:29385733). This biallelic loss-of-function mechanism aligns with the observed phenotype of rod degeneration and S-cone excess. A separate pediatric case report of suspected ESCS based on fundus examination and ERG further supports a role for NRL in this syndrome despite lack of molecular confirmation (PMID:37719593).

Current evidence comprises three genetically confirmed probands in two families, with consistent clinical and ERG findings but no extended segregation data. The association between NRL and ESCS is therefore classified as Limited; further studies in additional families and functional assays are needed to establish a definitive link. Key take-home: biallelic NRL variants should be considered in the genetic evaluation of patients presenting with ESCS features.

References

• Genes • 2018 • Autosomal Recessive NRL Mutations in Patients with Enhanced S-Cone Syndrome. PMID:29385733
• Cureus • 2023 • Suspected Enhanced S-Cone Syndrome: A Case Report. PMID:37719593

Evidence Based Scoring (AI generated)