Coloboma, also known as congenital ocular coloboma or uveoretinal coloboma, is an ocular abnormality that occurs before birth and is characterized by the absence of tissue parts in the structures that form the eye, including the iris, retina, choroid or the optic nerve.

Other abnormalities that individuals with coloboma may have include: macrophthalmia; eye cataracts; glaucoma; and vision problems such as myopia, nystagmus and retinal detachment. Some people have coloboma as part of a syndrome that affects other organs and tissues of the body. These forms are described as syndromic. When the coloboma occurs on its own, it is described as non-syndromic or isolated.

Colobomas that involve the eyeball should be distinguished from the clefts that occur in the eyelids. Although these fissures in the eyelids are also called colobomas, they arise from abnormalities in different structures at the beginning of development.

The coloboma arises from an abnormal development of the eye. During the second month of gestation, the choroidal fissure or embryonic fissure closes to form the structures of the eye. When the optical fissure does not close completely, the result is a coloboma. This anomaly may be due to changes in many genes involved in the development of the eye, most of which have not been identified. The condition may also be due to a chromosomal abnormality that affects one or more genes. Most of the genetic changes associated with the coloboma have been identified only in a very small number of affected individuals.

Many genes have been identified whose mutations can lead to coloboma. Among the genes identified are: ABCB6, ACTB, ACTG1, ALDH1A3, ATOH7, BCOR, BMP4, BMP7, C12orf57, CC2D2A, CHD7, CLDN19, CRIM1, CRYAA, CRYBA4, CRYBB2, DHX38, DPYD, ERCC1, ERCC5, FADD, FAM111A, FNBP4, FOXL2, FRAS1, FREM1, FREM2, FZD5, GDF3, GDF6, GJA1, GRIP1, HCCS, HMGB3, HMX1, IGBP1, KAT6B, KMT2D, LRP2, MAB21L2, MAF, MFRP, NAA10, OTX2, PAX2, PAX6, PDE6D, PIGL, POLR1C, POLR1D, PORCN, PQBP1, PRSS56, PTCH1, RAB3GAP1, RAB3GAP2, RARB, RAX, RBP4, RPGRIP1L, SALL1, SALL2, SALL4, SCLT1, SEMA3E, SHH, SIX3, SIX6, SMOC1, SOX2, SRD5A3, STRA6, TBC1D20, TBC1D32, TBX22, TCOF1, TENM3, TFAP2A, TMEM67, TMEM98, TMX3, VAX1, VSX2, YAP1, ZEB2, ZIC2.

In addition to genetic mutations, the risk of coloboma can also be increased by environmental factors that affect early development, such as exposure to alcohol during pregnancy. In these cases, affected people often have other health problems besides the coloboma.

In most cases, the isolated coloboma is not inherited. In cases where it is transmitted in families, the coloboma may have different inheritance patterns. The isolated coloboma is sometimes inherited with an autosomal dominant pattern, which means that a copy of an altered gene in each cell is sufficient to express the alteration. The isolated coloboma can also be inherited in an autosomal recessive pattern, which means that both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive coloboma each carry a copy of a mutated gene, but usually do not show signs and symptoms of the condition. Less often, the isolated coloboma may have dominant or recessive X-linked inheritance patterns. A characteristic of the X-linked inheritance is that parents cannot transmit X-linked traits to their children.

When the coloboma is presented as a characteristic of a genetic syndrome or a chromosomal abnormality, it can be grouped into families according to the inheritance pattern of that disease, which can be autosomal dominant, autosomal recessive or linked to the X chromosome.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with coloboma, by means of the complete PCR amplification of the exons of the genes in their development, 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).