- Clinical phenotype
- Key investigations
- Current research
- Further information and support
- Congenital cataract: for patients
|Genes involved (OMIM No.)||115 genes identified to date with the most common being:|
|Systemic features||Congenital cataract can be associated with various recognized syndromes, examples include: |
Lowe syndrome (OCRL-1)
|Molecular diagnosis||Next generation sequencing|
|Therapies under research|
Congenital cataract is a highly heterogenous disease with a broad aetiology. In bilateral cataract, a genetic cause can be identified in up to 90% of the cases.[2,3] Other important causes include:
- TORCH infections (Toxoplasma, Syphilis, Varicella Zoster, Parvovirus B19, Coxsackievirus, Rubella, Cytomegalovirus, Herpes simplex virus I and II); rubella is the most common infective cause worldwide
- Anterior uveitis secondary to juvenile idiopathic arthritis (JIA)
- Physical trauma
- Iatrogenic (e.g. steroids or radiation therapy) are important considerations but are relatively rare in this age group unless there is prolonged steroid use in atopy/JIA management[5,6]
Congenital cataract is defined as cataract present at birth or which occurs during the first year of life. It is also possible for children to develop cataract during childhood which has been classified in various ways (e.g. developmental, infantile or juvenile). However, such classification can be challenging as babies are usually asymptomatic at birth which may cause a delay in presentation. In the UK, cataracts are normally detected during newborn screening. The following features may be identified:
- Leukocoria (“white reflex”)
- Reduced or absent red reflex
Other associated ocular features
Majority of patients present with isolated cataract. However, it can be associated with other ocular abnormalities (complex ocular cataract). This is because environmental influences, or genes involved in the development or maintenance of the lens are also involved in other parts of the eye. At least 20 genes are associated with complex ocular cataract. The associated features include:
- Anterior segment dysgenesis (ASD)
- Corneal abnormalities (dystrophy or opacity)
- Iris hypoplasia
- Microphthalmia, anophthalmia, coloboma (MAC) spectrum
- Vitreoretinal dysplasia
Associated extraocular features
Various types of genetic mutations such as chromosomal abnormalities, loss-of-heterozygosity (loss of one of the two alleles in a loci/multiple locus), mitochondrial disorders and triplet repeats (a mutation with increasing number of trinucleotide repeats making the affected DNA segment unstable) can cause syndromic cataract.
The presence of cataract can be variable in syndromic cases. In some, it may not always be present or is only a part of a complex disease with multiple ocular and systemic pathologies such as Downs Syndrome (Trisomy 21).
In other diseases, it may be an initial or central feature such as:
- Lowe syndrome (OCRL-1) (cataract, intellectual disability and proximal tubular dysfunction)
- Zellweger spectrum disorder (a form of metabolic disorder caused by pathogenic mutations in 14 genes encoding proteins crucial to the formation and normal functioning of peroxisomes)
- Galactokinase disorder (GALK1)
- Cerebrotendinous Xanthomatosis (CYP27A1)
The identification of cataract is crucial in galactokinase disorder and cerebrotendinous xanthomatosis as disease halting/altering interventions are available.[8,9]
Pathogenic mutations in 115 genes have been identified so far causing congenital cataracts. All the identified causative genes encode proteins that play an important role in the development, structure or function of the lens. The main groups include crystallins, connexins, cytoskeletal structural proteins and transcription factors.  About 50% of non-syndromic cataracts are due to variants in genes encoding crystallin proteins. 
1) Examination of other family members
Performing dilated fundal examination in parents and sibling(s) may reveal mild cataracts (in autosomal dominant cases with reduced penetrance) or X-linked female carrier phenotypes which can direct further clinical and genetic investigations. For example, female carriers of Nance Horan syndrome usually display characteristic posterior Y-suture-centred lens opacities and variable degree of facial dysmorphism similar to affected males.
2) Ultrasound B-scan
To measure axial length, document microphthalmia and detect any posterior segment abnormalities.
Visual evoked potentials and full-field and pattern electroretinograms (ERG) can be considered to establish level of vision and exclude any retinal or optic disc dysfunction. Dense bilateral cataracts may make this examination challenging.
Due to the high likelihood of a genetic aetiology, children with bilateral congenital cataracts (or those with dysmorphic features and/or extraocular symptoms) should be referred to a paediatrician for a general assessment to exclude metabolic disorders, congenital infections, syndromic features or other potentially life-threatening causes. Some patients with no overt systemic features may require paediatric screening later on if a gene known to be associated with syndromic cataract is identified through genetic testing.
The assessment usually includes but not limited to:
- General physical examination including assessment of weight, height/length, head circumference and plotting of growth chart
- TORCH screen may be more appropriate in places where the prevalence of congenital infection is high*
- Blood tests to exclude metabolic disorders
- MRI brain and orbit imaging
- Echocardiogram/ electrocardiogram
- Renal ultrasound
*Note: The prevalence of congenital infections in the UK is low. Bilateral cataracts in a child born in the UK are more likely to have a genetic aetiology than an infectious one.[13,14] A targeted testing of components of the TORCH screen may be more appropriate after careful evaluation of the maternal antenatal history, the child’s co-morbidities and vaccination status.
Genetic testing is key so that a molecular diagnosis can be obtained to direct future management. This can be achieved through a variety of next generation sequencing (NGS) methods:
- Targeted gene panels (cataracts)
- Whole exome sequencing
- Whole genome sequencing
The diagnostic rate for bilateral cataracts using targeted gene panels have a diagnostic rate between 50-90%.[2,15] However, diagnostic rates can increase by a further 40% with whole genome sequencing.
1) Paediatric cataract surgery
The management of congenital cataract varies significantly from adult cataracts as many factors need to be taken into consideration, which include:
- Age of the child
- Unilateral/bilateral involvement
- Level of vision
- Timing of surgery
- Associated ocular abnormalities
- Adherence to the visual rehabilitation process (contact lens/glasses wear, amblyopia therapy, regular follow-ups)
- General health of the child
If the cataract is compromising visual development/visually significant, then removal of the opacified lens should be performed as soon as possible to avoid the risk of deprivation amblyopia. Surgery is usually delayed till after 6 weeks corrected age (even if the cataract is detected from birth) due to the higher risk of complications if operated earlier.[17,18] For children whom surgery may not be indicated (i.e. non-visually significant cataract), they should be closely monitored for the development of deprivation amblyopia.
Surgery usually involves lensectomy with/without anterior capsulotomy, posterior capsulotomy and anterior vitrectomy. Primary intraocular lens (IOL) implantation may be considered, or children may be left aphakic and the residual refractive error corrected with contact lenses/glasses. The main complications of surgery include:
- Visual axis opacification due to re-proliferation of lens material, pupillary membranes and/or visually significant corectopia requiring further surgery
- Development of secondary glaucoma
- Loss of accommodation
- Retinal detachment
Comparison of visual outcome and associated complications between primary IOL implantation and conventional treatment (aphakic correction with contact lenses/glasses) for both unilateral and bilateral cataracts have been studied in three large studies:
- Infant Aphakia Treatment Study (IATS) — A multicentre randomised clinical trial involving infants aged less than 7 months old with a unilateral congenital cataract
- IOLunder2 study — A multicentre prospective observational cohort study in children aged 2 years or younger with unilateral/bilateral congenital cataract
- The Toddler Aphakia and Pseudophakia study (TAPS) — A retrospective review of children aged 2 years or younger with unilateral/bilateral congenital cataract operated by IATS surgeons during the IATS enrolment period
The main findings of the studies were:
- Children under 2 years of age with bilateral cataracts that were operated on tend to have better visual outcome than those with treated unilateral cataract (5-year follow-up)[17,20]
- Medium (5 year) and long-term (10 year) visual outcomes were similar between both treatment options for unilateral (data up to 10 years) and bilateral cases (data up to 5 years) in children under 2 years of age (only up to a quarter of children achieved BCVA 6/12 or better in the IATS study)[17,20-22]
- Cataract removal (with/without primary IOL implantation) in children aged 1-6 months at time of surgery was associated with a higher risk of developing secondary glaucoma and visual axis opacification[17,22-24]
- Visual axis opacification was the most common adverse event associated with primary IOL implantation in children under 2 years of age with unilateral/bilateral cataracts (majority required additional surgery within the first year)[17,23]
- The TAPS study however suggested that primary IOL implantation in infants aged 7-24 months with unilateral cataract was safe with lower rates of complications and re-operations compared to the IATS study
- Primary IOL implantation did not protect against development of secondary glaucoma for unilateral (<7 months old) or bilateral (<2 years old) cases[17,20,24]
2) Post-operative visual rehabilitation/supportive management
- Regular monitoring of visual function
- Commencement of amblyopia treatment
- Correction of residual refractive errors
- Ensuring adherence to contact lens/glasses wear and amblyopia treatment
- Some may require referral to low vision services for extra support
- Monitoring for associated complications such as glaucoma and visual axis opacification which may require urgent intervention
Multidisciplinary management is required for children with systemic involvement and/or those who need extra support due to visual impairment. Paediatricians can help co-ordinate the various specialities involved and establish appropriate care pathways including support in the community.
Visual impairment at a young age can also have a negative impact on a child’s early general development. Therefore, timely referral to practitioners familiar with developmental surveillance and intervention for children with visual impairment (VI), such as developmental paediatricians as well as a Qualified Teacher of children and young people with Visual Impairment (QTVI) is crucial to optimise their developmental potential.
The Developmental Journal for babies and young children with visual impairment (DJVI) is a structured early intervention programme designed to track developmental and vision progress from birth to three years of age. It is mainly used by qualified healthcare professionals working in services providing support to babies and young children with VI in conjunction with the child’s parents.
Children with VI may be referred to specialist services such as the developmental vision clinic in the Great Ormond Street Hospital for Children or other specialist developmental services for further management.
Family management and counselling
Congenital cataract can be inherited via all Mendelian traits:
Emotional and social support
Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients in clinic. They provide emotional and practical support to help patients deal with their diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.
Referral to a specialist centre
In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research.
Current research is mainly focused on strengthening the genotype-phenotype correlations to help better understand the disease and related conditions. Other research aims to demonstrate the clinical utility of genetic testing in congenital cataract by facilitating the integration of genomic medicine into clinical practice and expanding testing services in the UK. This will invariably aid in the identification of novel genes and further contribute to genotype-phenotype studies.
- Research Opportunities at Moorfields Eye Hospital UK
- Searching for current clinical research or trials
- Rahi JS, Dezateux C, British Congenital Cataract Interest G. Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK. Invest Ophthalmol Vis Sci. 2001;42(7):1444-1448
- Patel A, Hayward JD, Tailor V, et al. The Oculome Panel Test: Next-Generation Sequencing to Diagnose a Diverse Range of Genetic Developmental Eye Disorders. Ophthalmology. 2019;126(6):888-907
- Shiels A, Bennett TM, Hejtmancik JF. Cat-Map: putting cataract on the map. Mol Vis. 2010;16:2007-2015
- Jyoti M, Shirke S, Matalia H. Congenital rubella syndrome: Global issue. J Cataract Refract Surg. 2015;41(5):1127
- Jobling AI, Augusteyn RC. What causes steroid cataracts? A review of steroid-induced posterior subcapsular cataracts. Clin Exp Optom. 2002;85(2):61-75
- Peled A, Moshe S, Chodick G. [Ionizing Radiation and the Risk for Cataract and Lens Opacities]. Harefuah. 2018;157(10):650-654
- Deng H, Yuan L. Molecular genetics of congenital nuclear cataract. Eur J Med Genet. 2014;57(2-3):113-122
- Coelho AI, Rubio-Gozalbo ME, Vicente JB, Rivera I. Sweet and sour: an update on classic galactosemia. Journal of inherited metabolic disease. 2017;40(3):325-342
- Amador MDM, Masingue M, Debs R, et al. Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes. Journal of inherited metabolic disease. 2018;41(5):799-807
- Pichi F, Lembo A, Serafino M, Nucci P. Genetics of Congenital Cataract. Dev Ophthalmol. 2016;57:1-14
- Shiels A, Hejtmancik JF. Molecular Genetics of Cataract. Prog Mol Biol Transl Sci. 2015;134:203-218
- Khan AO, Aldahmesh MA, Mohamed JY, Alkuraya FS. Phenotype-genotype correlation in potential female carriers of X-linked developmental cataract (Nance-Horan syndrome). Ophthalmic Genet. 2012;33(2):89-95
- de Jong EP, Vossen AC, Walther FJ, Lopriore E. How to use… neonatal TORCH testing. Arch Dis Child Educ Pract Ed. 2013;98(3):93-98
- Mc Loone E, Joyce N, Coyle P. TORCH testing in non-familial paediatric cataract. Eye (Lond). 2016;30(9):1275-1276
- Lenassi E, Clayton-Smith J, Douzgou S, et al. Clinical utility of genetic testing in 201 preschool children with inherited eye disorders. Genet Med. 2020;22(4):745-751
- Clark MM, Stark Z, Farnaes L, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16
- Solebo AL, Cumberland P, Rahi JS, British Isles Congenital Cataract Interest G. 5-year outcomes after primary intraocular lens implantation in children aged 2 years or younger with congenital or infantile cataract: findings from the IoLunder2 prospective inception cohort study. Lancet Child Adolesc Health. 2018;2(12):863-871
- Russell B, DuBois L, Lynn M, Ward MA, Lambert SR. The Infant Aphakia Treatment Study Contact Lens Experience to Age 5 Years. Eye Contact Lens. 2017;43(6):352-357
- Lim ME, Buckley EG, Prakalapakorn SG. Update on congenital cataract surgery management. Curr Opin Ophthalmol. 2017;28(1):87-92
- Bothun ED, Wilson ME, Vanderveen DK, et al. Outcomes of Bilateral Cataracts Removed in Infants 1 to 7 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry. Ophthalmology. 2020;127(4):501-510
- Lambert SR, Cotsonis G, DuBois L, et al. Long-term Effect of Intraocular Lens vs Contact Lens Correction on Visual Acuity After Cataract Surgery During Infancy: A Randomized Clinical Trial. JAMA Ophthalmol. 2020;138(4):365-372
- Bothun ED, Wilson ME, Traboulsi EI, et al. Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age: Toddler Aphakia and Pseudophakia Study (TAPS). Ophthalmology. 2019;126(8):1189-1195
- Plager DA, Lynn MJ, Buckley EG, Wilson ME, Lambert SR. Complications, adverse events, and additional intraocular surgery 1 year after cataract surgery in the infant Aphakia Treatment Study. Ophthalmology. 2011;118(12):2330-2334
- Freedman SF, Lynn MJ, Beck AD, Bothun ED, Örge FH, Lambert SR. Glaucoma-Related Adverse Events in the First 5 Years After Unilateral Cataract Removal in the Infant Aphakia Treatment Study. JAMA Ophthalmol. 2015;133(8):907-914
- Gillespie RL, O’Sullivan J, Ashworth J, et al. Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology. 2014;121(11):2124-2137 e2121-2122