Phenotypic and Genetic Spectrum in 309 Consecutive Pediatric Patients with Inherited Retinal Disease.

Area of Science:

• Ophthalmology
• Genetics
• Pediatrics

Background:

• Inherited retinal dystrophies (IRDs) are a significant cause of childhood blindness and visual impairment.
• IRDs can manifest with or without systemic conditions, complicating diagnosis and management.
• Understanding the age-specific phenotypic and genotypic spectrum is crucial for early intervention.

Purpose of the Study:

• To delineate the phenotypic and genotypic characteristics of IRDs in a pediatric cohort.
• To compare the spectrum of IRDs between preschool-aged and school-aged children.
• To identify key genes and clinical presentations associated with different age groups.

Main Methods:

• Retrospective, single-center, cross-sectional analysis of 309 pediatric patients with suspected IRD.
• Assessment of presenting symptoms, clinical phenotypes, and molecular genetic diagnoses.
• Grouping patients by age at genetic diagnosis: preschool (0-6 years) and schoolchildren (7-17 years).

Main Results:

• Preschoolers presented with nystagmus, lack of visual interest, or nyctalopia; schoolchildren with declining visual acuity, nyctalopia, or high myopia.
• Pathogenic variants were identified in 96 genes, with different distributions across age groups.
• Ciliopathies were the most common syndromic IRDs in both groups, with specific gene variants predominating in each age bracket.
• Leber's congenital amaurosis and stationary IRDs were frequent in preschoolers, while cone-dominated diseases were common in schoolchildren.

Conclusions:

• The genotypic and phenotypic spectrum of IRDs varies significantly between preschool and school-aged children.
• Syndromic and non-syndromic IRDs occur in nearly equal proportions in early childhood.
• Ophthalmic screening at preschool and school ages is vital for early diagnosis and management of sight-threatening conditions and potential systemic sequelae.