Clinical And Molecular Characterization Of Pediatrics Cataract, A 7 Years Experience Of A Pediatric Tertiary Center

Cataract is the most common treatable cause of childhood blindness. Childhood cataract could results from underlying genetic mutation which can be isolated ocular feature or associated with certain syndromes. To our knowledge, few is known in the genotypical and phenotypical correlation of pediatric cataract and their associated syndromes. Our study aims to assess the genetic profiles, clinical presentation, treatment modalities, complications and outcomes of pediatric cataract cases in a tertiary pediatric hospital.

This descriptive and cross-sectional study was conducted in King Abdullah Specialized Children Hospital, the largest pediatric referral center in Saudi Arabia. All pediatric cataract patients with genetically confirmed cataract mutations in the period from 2016-2022 were included in the study.

Suspected cases underwent cataract gene panel (AGK, CRYBA4, CRYBB1, COL18A1, EPHA2,  FYOC1, GNPAT, GRIA3, MAF, MT-CYB, PEX7, RAB3GAP1, and RAB3GAP2) sequence analysis. A total of 60 index cases were referred for cataract investigation. For subgroup analysis, we included patients who were diagnosed and confirmed genetically (n=28), and compared them with idiopathic cataract (n=32) after ruling out metabolic, traumatic, and infectious causes of lenticular opacity. Relevant demographic data, genetic data and ocular manifestations were collected and stratified into two groups namely: syndromic and non-syndromic cataract. Molecular profile was detected using CENTOGENE and GeneDx.

There were 13 mutated genes with CRYBB1 (42.9%) being the most common. Significant association was found between syndromic cataract and time of presentation (p-value= 0.016), optic nerve atrophy (p-value= 0.020), and nystagmus (p-value= 0.020). Cataract was congenital in majority of genetically confirmed cases (75%). About 56.3% of idiopathic cases had bilateral cataract. Certain characteristics showed statistically significant association with genetic cataract. Those include onset of cataract (p-value= 0.014), bilateral involvement (p-value= 0.001), Microphthalmia (p-value= 0.006), Microcornea (p-value= 0.003), vitreoretinochoroidopathy (p-value=0.028), overall number of complications (p-value= 0.019) and eye surgeries ( p-value=0.001).

This is by far the first analysis to address ocular and systemic features of syndromic versus non-syndromic cataract in such a comparative manner. Due to the higher rate of consanguinity marriage and autosomal recessive inheritance among Saudi families compared to the international populations, we recommend a national cataract preventive program. Genetically confirmed cataract has higher burden of ocular complications and surgical events compared to the idiopathic cataract. This study would fill a huge multidisciplinary gap and help physicians to identify clinical predictors of gene-phenotype related cataract. Further local studies are needed to explore focus predictors of anatomical and functional outcomes of cataract.