Keratoconus, also known as conical cornea or bulging cornea, is an ocular condition that affects the shape of the cornea progressively. The cornea of ​​affected individuals becomes thin and projects outward in a conical fashion. Over time, this anomaly can lead to myopia, irregular astigmatism and loss of vision.

Other common corneal changes include iron deposits in the cornea that form the so-called Fleischer ring and Vogt striae. As keratoconus progresses, affected people may develop scars.

The cause of keratoconus is unknown, although it is believed that various factors, both genetic and environmental, influence the risk of developing keratoconus. Environmental factors include excessive ocular rubbing and the tendency to develop allergic processes. It is estimated that about one third of individuals with keratoconus have an allergic process, although it is not clear how they are related to the development of keratoconus. Allergies can cause rubbing of the eyes, which can aggravate eye problems.

In most individuals with keratoconus, a combination of genetic and environmental factors is needed for the process to develop. In some cases, keratoconus is part of the characteristics related to genetic syndromes, such as congenital Leber's amaurosis and arterial tortuosity syndrome.

Changes in multiple genes have been associated with the development of keratoconus. Many of these variants have been found only in small populations or isolated families. These genes include: CAST (calpastatin), COL4A3 (collagen type IV alpha 3 chain), COL4A4 (collagen type IV alpha 4 chain), COL5A1 (collagen type V alpha 1 chain), DOCK9 (dedicator of cytokinesis 9), FNDC3B (fibronectin type III domain containing 3B), FOXO1 (forkhead box O1), HGF (hepatocyte growth factor), IL1A (interleukin 1 alpha), IL1RN (interleukin 1 receptor antagonist), LOX (lysyl oxidase), MIR184 (microRNA 184), RAB3GAP1 ( RAB3 GTPase activating protein catalytic subunit 1), SLC4A11 (solute carrier family 4 member 11), TGFBI (transforming growth factor beta induced), VSX1 (visual system homeobox 1), WNT10A (Wnt family member 10A), ZEB1 (zinc finger E- box binding homeobox 1) and ZNF469 (zinc finger protein 469).

These genes have varied functions. The genes most frequently associated with this process play roles in the development of the eye, the formation and structure of the cornea, the extracellular matrix, the process of inflammation and the regulation of cell growth. It is believed that an interruption in one of these processes, in combination with an environmental trigger, can lead to the development of keratoconus.

In most cases, keratoconus is not inherited and develops in individuals with no family history. In some cases, keratoconus is inherited with an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the process. Often, affected people have an affected parent, although some people who have a genetic variant never develop the disorder. Keratoconus can also be inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have the mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with keratoconus, by means of the complete PCR amplification of the exons of the CAST, COL4A3, COL4A4, COL5A1, DOCK9, FNDC3B, FOXO1, HGF, IL1A, IL1RN, LOX, MIR184, RAB3GAP1, SLC4A11, TGFBI, VSX1, WNT10A, ZEB1 y ZNF469 genes, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).