Genetically determined eye diseases

Ophthalmic genetics is a branch of medicine that studies hereditary eye disorders and helps identify their genetic causes, understand their mechanisms, and develop diagnostic and treatment strategies.

Findings from genetic testing in ophthalmology are increasingly important for individual eye care, enabling personalized treatment and predicting the risk of eye disease not only in the family, but also in the general population.

Genetic eye disorders can be inherited in a way:

• Autosomal dominant (mutation occurs in a single gene). In autosomal dominant inheritance, a person who has inherited a defective copy of the gene from one parent will have symptoms of the disease regardless of whether the other copy of the gene is normal or not – a dominant mutation is sufficient to cause the disease. Diseases inherited in this way include, for example, Marfan syndrome, Stickler syndrome, Alport syndrome (this type of inheritance accounts for about 1% of all cases) and also some forms of cataracts or macular degeneration.

• Autosomal recessive (for the disease to develop, both copies of the gene on the autosomes must be defective). Some forms of cataracts or retinal dystrophies are inherited in this way. This type of inheritance also affects about 15% of cases of Alport syndrome.

• Sex-coupled (the gene responsible for the disease is located on the X or Y sex chromosomes). Since women have two X chromosomes and men have one X chromosome and one Y chromosome, the inheritance of sex-linked disease differs between the sexes. Men who inherit a defective copy of the gene on their only X chromosome are more susceptible to the disease than women. This is because women have a second, healthy X chromosome that can act as a safety net. Men, whose only X chromosome contains a defective gene, often develop symptoms of the disease. Eye diseases inherited in a sex-linked manner include Alport syndrome (85% of cases) and Lowe’s syndrome.

• Mitochondrial. Mitochondrial inheritance refers to the transmission of genetic mutations that are found in mitochondrial DNA (mtDNA), which is inherited from the mother. Mitochondrially inherited diseases can include damage to various organs, including the organ of sight. An example of mitochondrially inherited diseases is Leber’s optic neuropathy (LHON), which leads to gradual vision loss associated with damage to the optic nerve.

Marfan syndrome

Ocular manifestations in Marfan syndrome can include myopia, lens subluxation (dislocation) and displacement, and cataracts. Lens subluxation and displacement are due to weaknesses in the connective tissue that, in a normal anatomical state, holds the lens in proper alignment by means of ligaments.

Stickler syndrome

Stickler syndrome is often diagnosed with either myopia or hyperopia, which may be accompanied by astigmatism and the risk of retinal detachment. Some people with Stickler syndrome suffer from congenital cataracts.

Patients are also exposed to:

• Degeneration of the vitreous body in the eye,
• The movement of the eyes independently of each other (nystagmus),
• Glaucoma.

Alporta team

In the course of Aplort syndrome, there are abnormalities in the structure of the eye. Most often, the structure of the lens is abnormal, but there can also be abnormalities in the retina and cornea. When the retina is damaged, there are problems with central vision (blurred vision of objects in the center of the visual field).

Lowe’s syndrome (ocular and cerebral-renal dystrophy)

Ophthalmic disorders in Lowe’s syndrome include bilateral congenital choroidal cataracts, glaucoma with or without goitre, strabismus, hyperopia, and corneal and conjunctival scarring. Some people with Lowe’s syndrome may have corneal changes such as cysts or delayed corneal growth.

De Morsier syndrome (septal-eye dysplasia)

Ocular disorders are based on optic nerve hypoplasia (ONH). Hypoplasia of the II (optic) nerve can occur singly, in one eye, or in both eyes. Symptoms can be very severe up to and including total blindness.

Leber’s optic neuropathy (LHON)

The onset of the disease usually occurs between 15. 35. year of age. It manifests itself as a slow loss of vision, initially in one eye and over the next few weeks or months in the other. The decline in visual acuity is usually significant. There is also abnormal color recognition and an abnormal pupillary response to light, and in the acute phase also an abnormal image of the optic nerve disc and mild dilatation and tortuosity of the capillaries on its surface.