Congenital cataract: a guide to genetic and clinical management

Abstract

Worldwide 20,000–40,000 children with congenital or childhood cataract are born every year with varying degrees and patterns of lens opacification with a broad aetiology. In most cases of bilateral cataract, a causative genetic mutation can be identified, with autosomal dominant inheritance being most common in 44% of cases. Variants in genes involve lens-specific proteins or those that regulate eye development, thus giving rise to other associated ocular abnormalities. Approximately 15% of cases have systemic features, hence paediatric input is essential to minimise comorbidities and support overall development of children at high risk of visual impairment. In some metabolic conditions, congenital cataract may be the presenting sign, and therefore prompt diagnosis is important where there is an available treatment. Multidisciplinary management of children is essential, including ophthalmic surgeons, orthoptists, paediatricians, geneticists and genetic counsellors, and should extend beyond the medical team to include school and local paediatric visual support services. Early surgery and close follow up in ophthalmology is important to optimise visual potential and prevent amblyopia. Routine genetic testing is essential for the complete clinical management of patients, with next-generation sequencing of 115 genes shown to expedite molecular diagnosis, streamline care pathways and inform genetic counselling and reproductive options for the future.Lay abstractChildhood cataract: how to manage patients Cataract is a clouding of the lens in the eye. Cataract occurring in children has many different causes, which may include infections passed from mother to child during pregnancy, trauma, medications and exposure to radiation. In most cases of cataract occurring in both eyes, a genetic cause can be found which may be inherited from parents or occur sporadically in the developing baby itself while in the womb. Cataracts may occur on their own, with other eye conditions or be present with other disorders in the body as part of a syndrome. Genetic testing is important for all children with cataract as it can provide valuable information about cause, inheritance and risk to further children and signpost any other features of the disease in the rest of the body, permitting the assembly of the correct multidisciplinary care team. Genetic testing currently involves screening for mutations in 115 genes already known to cause cataract and has been shown to expedite diagnosis and help better manage children. Genetic counselling services can support families in understanding their diagnosis and inform future family planning. In order to optimise vision, early surgery for cataract in children is important. This is because the brain is still developing and an unobstructed pathway for light to reach the back of the eye is required for normal visual development. Any obstruction (such as cataract) if left untreated may lead to permanent sight impairment or blindness, even if it is removed later. A multidisciplinary team involved in the care of a child with cataract should include ophthalmic surgeons, orthoptists, paediatricians, geneticists and genetic counsellors, and should extend beyond the medical team to include school and local child visual support services. They will help to diagnose and manage systemic conditions, optimise vision potential and help patients and their families access best supportive care.