Cataract refers to the clouding of the lens in the eye, defined as opacification of the normally transparent crystalline lens. Cataracts are common in older people and usually related to aging. They can be classified by the age at onset as congenital or infantile (<1yr); juvenile cataract (1-10yrs); presenile cataract (<45yrs) and senile or age-related cataract (>45yrs)1.
It is important to determine if the individual has non-syndromic (only the lens are affected) or syndromic (other organs in addition to the lens are affected) congenital cataracts. The most common causes of non-syndromic congenital cataracts are pathogenic variants in lens crystallin - associated genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD) which account for ~50% of all cases1, 2, 4.
Autosomal dominant, autosomal recessive
1-6/10,000 for congenital cataract1; 1-15/10,000 in children 1, 3.
Major signs and symptoms of cataracts include 1, 3, 4:
- Clouded, blurred or dim vision
- Increasing difficulty with vision at night
- Sensitivity to light and glare
- Need for brighter light for reading and other activities
- Seeing "halos" around lights
- Frequent changes in eyeglass or contact lens prescription
- Fading or yellowing of colors
- Double vision in a single eye
- Visual acuity test.
- Slit-lamp examination.
- Retinal exam.
- Diagnosis is confirmed by the finding of pathogenic variant in one of the following genes: AGK, BCOR, BFSP1, BFSP2, CHMP4B, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGB, CRYGC, CRYGD, CRYGS, CTDP1, EPHA2, EYA1, FOXC1, FOXE3, FTL, FYCO1, GALK1, GCNT2, GJA3, GJA8, HSF4, LEMD2, LIM2, LSS, MAF, MIP, NHS, P3H2, PAX6, PITX3, SIPA1L3, SLC16A12, TDRD7, UNC45B, VIM, VSX2, WFS1.
The only effective treatment for cataracts is surgery 1, 2.
- Corneal disease
- Optic nerve disease
- Eye injury, eye tumors
- Macular disease
- Medications affecting central nervous system
To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for cataract using NGS Panel Genomic:
Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the cataract panel. Copy Number Variants analysis derived from NGS data is also included.
Step 2: If no pathogenic variant is identified in Step1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.
- Individuals with early onset of cataracts.
- Individuals with a positive family history of cataract.
- Individuals with most common symptoms suggestive of cataracts (regardless of family history).
Confirmation of a clinical diagnosis through genetic testing of cataract can allow for genetic counseling and may direct medical management.
Table 1: Overview of genes included in Cataract panel
|Gene||OMIM (Gene)||Associated diseases (OMIM)||Inheritance||CentoMD® exclusive variant numbers (++)|
|AGK||610345||Sengers syndrome; autosomal recessive cataract type 38||AR||5|
|BCOR||300485||Microphthalmia, syndromic 2||XLD||10|
|BFSP1||603307||Cataract 33, multiple types||AD, AR||1|
|CRYAA||123580||Cataract 9, multiple types||AD, AR||1|
|CRYAB||123590||Myopathy, myofibrillar, 2; Cataract 16, multiple types; Myopathy, Myofibrillar, Fatal Infantile Hypertonic, Alpha-B Crystallin-Related; dilated cardiomyopathy-1II||AD, AR||1|
|CRYBB1||600929||Cataract 17, multiple types||AD, AR||4|
|CRYBB3||123630||Cataract 22, autosomal recessive||AD, AR||1|
|CRYGC||123680||Cataract 2, multiple types||AD||1|
|CTDP1||604927||Congenital cataracts, facial dysmorphism, and neuropathy||AR||28|
|EPHA2||176946||multiple types cataract type 6||AD||2|
|EYA1||601653||Branchiootorenal Syndrome 1; Otofaciocervical Syndrome 1; Branchiootic syndrome 1||AD||2|
|FOXC1||601090||Iridogoniodysgenesis, type 1; Axenfeld-Rieger syndrome, type 3||AD||5|
|FOXE3||601094||Anterior segment dysgenesis 2, multiple subtypes; Cataract 34, multiple types||AD, AR||1|
|FTL||134790||Hyperferritinemia With Or Without Cataract; neurodegeneration with brain iron accumulation 3||AD, AR||4|
|FYCO1||607182||Cataract 18, autosomal recessive||AR||10|
|GCNT2||600429||Cataract 13 with adult i phenotype||AD, AR||6|
|GJA8||600897||Cataract 1, multiple types||AD||3|
|HSF4||602438||Cataract 5, multiple types||AD||2|
|MAF||177075||Cataract, pulverulent or cerulean, with or without microcornea||AD||1|
|NHS||300457||Nance-Horan syndrome||XL, XLD||8|
|PAX6||607108||Aniridia 1; foveal hypoplasia type 1||AD||18|
|PITX3||602669||Anterior segment mesenchymal dysgenesis; Cataract 11, multiple types||AD, AR||0|
|TDRD7||611258||Cataract type 36||AR||7|
|UNC45B||611220||Cataract type 43||AD||2|
|VSX2||142993||microphthalmia with coloboma 3; isolated microphthalmia 2||6|
|WFS1||606201||noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; Wolfram syndrome; Deafness, autosomal dominant 6/14/38; Wolfram-like syndrome||AD, AR||21|