X- Linked Retinopathy: An Overview

Introduction

X-linked or sex-linked retinopathies occur due to mutations in specific genes. Certain genes help in the synthesis of proteins that help in the functioning of the retina of the eye and help in proper vision. The early symptoms develop during childhood, and symptoms worsen over time. There are several types of x-linked retinopathy based on the specific genes and the lack of proteins synthesized.

What Is X-Linked Disease?

X- linked diseases refer to genetics, the diseases or syndromes associated with mutations of the X chromosome. Humans have two sets of sex chromosomes, X and Y. Females have two sets of X chromosomes and males have one X and one Y chromosome. In X linked to the type of inheritance, males are more commonly affected and have only one set of mutated X chromosomes. In females, only one X chromosome is affected, and another X chromosome is nonmutated or normal.

The X-linked diseases can be manifested in X-linked dominant or recessive forms.

• X-linked Dominant Disorders: It is caused by a mutation in only one copy of the gene. In males, the variation in one copy of the gene in each cell can cause the disease. In females with two sets of X chromosomes, the variation in any one of the copies of the gene is required to cause the disorder.

• X-linked Recessive Disorder: X-linked recessive disorder in males, causes the alternation of one copy of the gene and causes the condition. In females to have the condition they need an alternation of genes in both the X chromosomes. Because of the presence of one X-linked chromosome, males are commonly affected by X-linked recessive disorders. A feature of X-linked inheritance is that fathers cannot pass the X-linked traits to their sons. There is no male-to-male transmission

What Is X-Linked Retinopathy?

Inherited retinopathic diseases are a cause of blindness in pediatrics and among working groups of people in many countries. Pathogenic variations occur and cause disease through a loss of protein function. These diseases can be managed by gene replacement strategies.

• X-linked retinopathies are a group of monogenic retinal disease that occurs due to variation in a single gene, resulting in the gradual loss of photoreceptor cells leading to blindness.

• The X-linked retinopathies include progressive conditions or stationery or can be with or without syndromic features. Female carriers exhibit a group of symptoms that helps in the diagnosis and helps to know insights about the disease.

• The X-linked retinopathies occur due to the loss of function of certain proteins that codes for a particular function.

What Are the Various Genes Associated With X-Linked Retinopathy?

• RPGR gene associated with retinitis pigmentosa, cone, and cone-rod dystrophy, which affects the retina causes vision loss and becomes severe over time.

• RP2 gene is associated with retinitis pigmentosa, which is a degenerative eye disease causing vision impairment.

• CHM gene is associated with choroideremia, commonly affecting males characterized by chorioretinal degeneration.

• RS1gene is associated with X-linked retinoschisis, commonly affecting young boys and causing early vision loss.

• NYX gene is associated with complete congenital stationary night blindness (CSNB), which is a retinal disorder and causes night blindness (choroideremia).

• CACNA1F gene associated with incomplete CSNB.

• OPN1LW/OPNIMW gene associated with blue cone monochromacy Bornholm eye disease causing color vision defects with high myopia and cone dystrophy affecting the color sensitive area of the eye.

• The GPR143 gene is associated with ocular albinism causing reduced pigmentation of the iris and affecting vision.

• NDP gene is associated with Norrie disease, causing blindness in male infants soon after birth, and X-linked familial exudative vitreoretinopathy (FEVR), which is a heredity vision loss causing progressive vision loss.

What Are the X-Linked Retinopathies Associated With the RPGR Gene?

• The RPGR gene is called retinitis pigmentosa GTPase regulator is a gene that provides information about an essential protein that codes for normal vision. The protein helps in the proper functioning of the cilia, which is necessary for the perception of sensory information, including hearing, smell, and vision.

Health conditions associated with genetic changes are

1. Retinitis Pigmentosa:

RPGR gene mutations cause an X-linked form of retinitis pigmentation. This condition primarily affects males, causing night blindness at a very young age followed by progressive daytime vision loss. 70 percent of the RPGR gene mutations cause X-linked retinitis pigmentosa. Retinitis pigmentosa often shows an autosomal dominant inheritance pattern, where only one copy of the mutated gene is required to cause the disorder, or it can show an autosomal recessive pattern of inheritance. The syndromes associated are

• Rod-cone dystrophy.

• Cone dystrophy.

• Cone-rod dystrophy.

Clinical features include night blindness, visual field constriction, central visual loss, myopia, hearing loss, sinusitis, asthma, chronic respiratory infections, and infertility.

2. Rod-cone Dystrophy:

Rod-cone dystrophy is a group of eye disorders causing loss of vision and becoming more severe over time. There are more than 30 types of rod-cone dystrophies. Affecting the retina, the light-sensitive layers of the eye and sensitive cells of the retina deteriorate gradually.

The first sign and symptoms occur in childhood and are

• Decreased sharpness of vision.

• Increased sensitivity to light.

• Impaired color vision.

• Blind spots.

• Partial side vision loss.

• By mid-adulthood, the visual acuity decreases and makes the individual legally blind. As conditions worsen, individuals develop involuntary eye movements. The most common rod-cone dystrophy is called retinitis pigmentosa.

What Is the X-Linked Retinopathy Associated With the CHM Gene?

CHM genes provide information for the protein called rab escort protein-1 (REP-1). Vision problems occur due to the loss of specialized light-sensitive tissue at the back of the eye. More than 140 mutations in the CHM gene cause choroideremia.

• Choroideremia:

Choroideremia shows progressive vision loss that affects males. It shows an X-linked recessive pattern. The first symptom shown during early childhood is night blindness. Individuals with this symptom develop blindness in late adulthood.

Choroideremia usually affects males, and the affected females are carriers.

What Is Retinopathy Associated With the RS1 Gene?

The RS1 gene codes for the retinoschisis 1 protein in the retina. It shows an X-linked recessive pattern. The retinoschisis binds to the surface of specialized cells in the retina that detect color and light. More than 220 mutations in the RS1 gene cause X-linked juvenile retinoschisis. This disorder causes tiny splits or tears in the retina, causing vision loss. The disruption in retinoschisis protein production or function causes alterations in the maintenance and organization of the retina.

Conclusion

Several therapies have been under clinical research and may come up in the coming years. These treatment options aim to slow down the disease progression and minimize the loss of visual function. Gene therapy is the most advanced therapeutic procedure for X-linked retinopathy.