Clinical AreaOphthalmology

Here you will find the disease-related gene panels available for the clinical area specified above.

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Many hereditary eye diseases are rare, but overall genetic vision disorders are very common in children and adults. To date, several hundred genes have been characterized that cause hereditary eye diseases such as albinism, aniridia, color blindness, corneal dystrophies, glaucoma, Leber's congenital amaurosis, microphthalmia, night blindness, retinitis pigmentosa and retinoblastoma. In syndromal eye diseases, the symptoms of the eye are part of a primary disease that affects several organ systems or functions of the body. More than 60% of childhood blindness may be genetic, associated with eye malformations, congenital glaucoma, atrophy of the optic nerve and retinal diseases such as retinitis pigmentosa. In adults, genetic factors can also be (partly) responsible for eye diseases such as glaucoma, retinitis pigmentosa and macular degeneration. Genetic diagnostics are used to clarify the causes of hereditary eye diseases. The aim here is to detect deviations from the reference genome ("wild type") and then, if necessary, to distinguish between neutral variants and pathogenic mutations. For example, mutations in independent genes on different chromosomes can cause >80 clinically practically indistinguishable forms of retinitis pigmentosa ("locus heterogeneity"). On the other hand, different mutations in one and the same gene lead to clinically apparently separated disease entities ("allele heterogeneity"; TULP1 gene mutations cause retinitis pigmentosa type 14 or Leber congenital amaurosis type 15).

Formal genetically and etiologically the following groups of hereditary eye diseases can be distinguished:

• monogenic diseases (autosomal or X-chromosomal inheritance), caused by alteration(s) of a single gene
• mitochondrial diseases (maternal or autosomal inheritance), leads to disturbance of the energy metabolism of the cells
• digenic diseases, which are only manifested when mutations are simultaneously present in heterozygous state in two different genes. Physiologically the two normal gene products together form functional heterodimers. Digenic inheritance affects ~3% of hereditary diseases in addition to the classic autosomal and X-linked diseases.
• multifactorial diseases (interaction of several to many genes plus environmental factors), applies to many common eye diseases such as age-related macular degeneration, strabismus and some forms of glaucoma, myopia and astigmatism. Below some of the more common disease groups are mentioned.

Isolated forms of congenital cataract are often inherited as a autosomal dominant trait. In contrast, syndromal forms are often inherited autosomal recessively, e.g. in the context of a hereditary metabolic disorder. Comprehensive gene panels are available for differential diagnostic purposes. Glaucoma can also be congenital (e.g. in aniridia) or occur in infancy, and it is usually bilateral. Early diagnosis via a gene panel is often crucial for treatment success. Retinoblastoma is a malignant tumor of the retina in childhood, 45% of patients have a hereditary form. These patients are heterozygous carriers of a mutation in the RB1 gene.

Optic atrophies have, both, non-genetic and genetic causes. Leber's optic neuropathy, on the other hand, is caused by variants in the mitochondrial genome, and it is inherited maternally. The most frequent form of optic atrophy is autosomal-dominantly inherited with onset in childhood. An important basis for the diagnosis is therefore the family history in order to select an appropriate gene panel.

Corneal dystrophies are genetically determined diseases of the cornea, typically bilateral with progressive clouding of the cornea. The opacities have different characteristic forms for the respective disorder. Thus, point, spot, spotted, lattice, honeycomb, cloudy, flat and crystal-like clouding can be distinguished. In most cases corneal dystrophies are detected before the age of 40 during ophthalmological examinations. The inheritance of most corneal dystrophies is autosomal dominant.

Hereditary retinal diseases, like retinitis pigmentosa (retinopathia pigmentosa), can first affect the function of the rod photoreceptors in the retinal periphery. Cone dystrophies affect the function of the cone photoreceptors and start in the centre of the retina. Many retinal diseases affect, both, rod and cone receptor functions. Macular dystrophies are a group of genetic retinal diseases that affect only the cone receptors of the macula as the site of sharpest vision. Ophthalmologically characteristic changes in the retina, visual field examination and electrophysiological diagnostics often point to the clinical classification of the various retinal diseases. The corresponding gene panels are therefore particularly expanded.

The genetic diagnosis supports and confirms the clinical diagnosis. This is very important for some visual disorders when diseases with similar clinical symptoms but different causes need to be differentiated. Examples are hereditary retinal diseases or diseases of the optic nerve. A correct diagnosis is often crucial to correctly assess the prognosis, avoid unnecessary examinations and also unsuitable therapies. Once the genetic cause of an eye disease has been identified, family members who may be carriers but may not yet have symptoms can be genetically examined. With this information, it is possible to offer genetic counselling to patients and the family. For certain diagnoses, the genetic findings also make it possible to identify candidates for modern cell and gene therapies.