Leber Congenital Amaurosis 10 (LCA10) represents a severe early-onset retinal dystrophy that can sometimes present with complex features. In a recent breakthrough case, researchers identified a rare co-occurrence of dual molecular mutations in an infant. Initially, clinicians suspected Bardet-Biedl syndrome (BBS) due to the presence of nystagmus and postaxial polydactyly. However, further genetic investigation revealed a more nuanced reality involving two distinct genetic disorders.

The Diagnostic Journey of Leber Congenital Amaurosis 10

A six-month-old female infant presented with nystagmus and an absence of visual tracking. Furthermore, she exhibited postaxial polydactyly. Initial targeted gene panel testing detected compound heterozygous pathogenic variants in the CEP290 gene. Consequently, doctors assigned a preliminary diagnosis of Bardet-Biedl syndrome. Over a six-year follow-up period, the patient developed progressive pigmentary retinopathy. Nevertheless, she did not manifest other classic systemic features of BBS, such as obesity or renal issues.

A detailed review of the family history revealed that the father also had polydactyly. Because of this critical finding, clinicians performed whole-exome sequencing (WES). This testing identified an additional likely pathogenic variant in the GLI3 gene. The patient inherited this mutation from her father. Therefore, the polydactyly existed as an isolated trait unrelated to the retinal disease.

Clinical Implications and Genetic Testing

The final diagnosis confirmed LCA10 alongside isolated postaxial polydactyly type A1. This case highlights how WES provides superior diagnostic utility over targeted panels in complex pediatric cases. Accurate differentiation is vital because LCA10 has a more favorable systemic prognosis than syndromic ciliopathies. Additionally, emerging gene therapies now target patients with LCA10. Practitioners must emphasize longitudinal phenotyping and meticulous family histories to avoid misdiagnosis.

Frequently Asked Questions

How does Leber Congenital Amaurosis 10 differ from Bardet-Biedl Syndrome?

LCA10 primarily affects the retina and does not typically involve the systemic multi-organ features seen in BBS, such as obesity, renal anomalies, or polydactyly.

Why is whole-exome sequencing preferred over targeted panels?

WES can identify mutations in multiple unrelated genes. This is crucial for cases where independent genetic conditions coexist and mimic a single syndrome.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice or a professional relationship. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Wang L et al. Dual molecular diagnosis of CEP290 and GLI3 mutations identified in an infant with leber congenital amaurosis and postaxial polydactyly, a Bardet-Biedl syndrome phenocopy. BMC Ophthalmol. 2026 Feb 18. doi: 10.1186/s12886-026-04675-2. PMID: 41703510.

Beales PL et al. New criteria for improving the clinical diagnosis of Bardet-Biedl syndrome. J Med Genet. 1999;36(6):437-446.

Cideciyan AV et al. Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain. Invest Ophthalmol Vis Sci. 2017;58(5):2609-2622.