Last updated: June 14, 2021
Years published: 1991, 1999, 2007, 2010, 2021 Source Link: https://rarediseases.org/rare-diseases/cone-dystrophy/
Acknowledgment
NORD gratefully acknowledges Nivi Ahlawat, MS, NORD Editorial Intern from the Stanford University MS Program in Human Genetics and Genetic Counseling and Jennefer Kohler, MS, LCCG, Clinical Instructor (Affiliated), Department of Pediatrics, Division of Medical Genetics, Stanford University, for assistance in the preparation of this report.
DISEASE OVERVIEW
Summary
Cone dystrophy is a general term used to describe a group of rare eye disorders that affect the cone cells of the retina. Cone dystrophy can cause a variety of symptoms including decreased visual clarity (acuity), decreased color perception (dyschromatopsia), and increased sensitivity to light (photophobia). There are two main forms of cone dystrophy: stationary cone dystrophy and progressive cone dystrophy. In stationary cone dystrophy, symptoms tend to remain stable and are usually present at birth or early childhood. In progressive cone dystrophy, symptoms slowly worsen over time. The age of onset, progression and severity of cone dystrophy can vary greatly from one person to another, even among individuals with the same type of cone dystrophy. Some forms of cone dystrophy are inherited; other forms appear to occur by chance for no apparent reason (sporadically).
A variety of different and confusing names have been used to describe the various forms of cone dystrophy. Some researchers limit the term “cone dystrophy” to the progressive forms of the disorder. Other researchers use cone dystrophy as an umbrella term for both the stationary and progressive forms of cone dystrophy – examples of which include achromatopsia, incomplete achromatopsia, blue cone monochromatism and X-linked progressive cone dystrophy. This report is a general overview of stationary and progressive cone dystrophy. For more specific information on an individual form of cone dystrophy, use the disorder’s specific name as your search term in the Rare Disease Database or contact one of the organizations listed in the resources section of this report.
SYNONYMS
retinal cone degeneration
retinal cone dystrophy
SUBDIVISIONS
progressive cone dystrophy
stationary cone dystrophy
SIGNS & SYMPTOMS
The symptoms of cone dystrophy may vary from one person to another, even among individuals with the same form of the disorder. The age of onset, specific symptoms, severity and progression (if any) can vary greatly. The amount of vision loss varies and is difficult to predict. Affected individuals should talk to their physician and medical team about their specific case and associated symptoms.
Cone dystrophy results from damage to the cone cells of the retinas. The retinas are the thin layers of nerve cells that line the inner surface of the back of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. The retina has two main types of cells: cones and rods. Cone and rod cells are called photoreceptors because they detect and respond to light stimuli.
Cone cells are located throughout the retina. The highest concentration of cone cells is clustered in the oval-shaped, yellowish area near the center of the retina (macula). Cone cells are involved in the part of vision that enables a person to see fine details, read or recognize faces. Cone cells also play a role in the perception of color. Cone cells function best in bright light. Rod cells are found throughout the retina except in the center. Rod cells enable people to see in low or limited light.
Cone dystrophy is sometimes broken down into two broad groups: stationary and progressive. Stationary cone dystrophy is usually present during infancy or early childhood and symptoms usually remain the same throughout life. In progressive cone dystrophy, associated symptoms become worse over time. Progressive cone dystrophy usually develops in late childhood or early during adulthood. However, the rate of progression and age of onset can vary greatly from one person to another.Damage to cone cells can result in decreased clarity of vision (reduced visual acuity) when looking straight ahead (central vision), a reduced ability to see colors and an abnormal sensitivity to light (photophobia). Some affected individuals may not be able to see color at all and some may develop rapid, involuntary eye movements (nystagmus).
In the progressive form of cone dystrophy, vision continues to deteriorate over time. In many cases vision may deteriorate so that a person is considered “legally” blind (i.e., vision that is 20/200 or worse). Complete blindness is uncommon in individuals with cone dystrophy. Side (peripheral) vision is usually unaffected as well. Individuals with cone dystrophy can usually see well at night or in low light situations because the rod cells are usually unaffected. In rare cases, late in the disease course, some rod cells may become involved.
CAUSES
Many cases of cone dystrophy occur randomly for no identifiable reason (sporadically). Some forms are inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Inherited forms of cone dystrophy are due to changes (mutations) in one of several genes that have been linked to cone dystrophy. These genes contain instructions for making proteins that play vital roles in the development, function and overall health of cone cells. The exact underlying mechanisms that cause cone dystrophy are not fully understood.
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly in males. Females that have a non-working gene copy on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the non-working gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
A male with an X-linked disorder will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
Less often, cone dystrophy may be inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene copy from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
AFFECTED POPULATIONS
Cone dystrophy affects males and females in equal numbers when it occurs sporadically or is inherited in an autosomal dominant or recessive pattern. The X-linked form of cone dystrophy only affects males fully, although some females may have mild symptoms of the disorder. The exact incidence of cone dystrophy is unknown. Most sources estimate that the condition affects 1 in 30,000 individuals in the general population.
DISORDERS WITH SIMILAR SYMPTOMS
Symptoms of the following disorders can be similar to those of cone dystrophy. Comparisons may be useful for a differential diagnosis.
Cone-rod dystrophies are a group of rare eye disorders that affect both the cone and rod cells of the retina. In some cases, individuals experience deterioration of the cone cells more severely than the rod cells. In these cases, the initial symptoms are decreased clarity (acuity) of vision when looking straight ahead (central), loss of the ability to perceive color, and an abnormal sensitivity to light (photophobia). When the rod cells become more involved, affected individuals experience a decreased ability to see at night or in low light situations and may lose the ability to see clearly to the sides (peripheral vision). In rare cases, cone and rod cells deteriorate simultaneously and these symptoms occur at approximately the same time. Most cases of cone-rod dystrophies occur due to mutations of certain genes. Several different genes have been linked to cone-rod dystrophy. Cone-rod dystrophies can be inherited in an autosomal recessive, dominant, X-linked or mitochondrial pattern.
Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth or lose their sight within the first few years of life. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or abnormal protrusion of the front (anterior), clear portion of the eye through which light passes (cornea) (keratoconus). In addition, some infants with complicated syndromes from other genes may exhibit hearing loss, intellectual disability, and/or a delay in the acquisition of skills that require the coordination of mental and muscular activity (developmental delay). LCA is usually inherited in an autosomal recessive pattern. Several genes have been found to be involved in LCA. (For more information on this disorder, choose “Leber Congenital Amaurosis” as your search term in the Rare Disease Database.)
Stargardt disease is a rare juvenile form of macular degeneration. Macular degeneration is a general term for a group of eyes disorders characterized by the deterioration of the oval-shaped yellow spot (macula) near the center of the retina. The macula is essential for proper vision when looking straight ahead (central vision) and with seeing fine details. Some individuals with Stargardt disease may experience symptoms during childhood, while other individuals with this condition may not experience symptoms until their 30s or 40s. Central vision is usually affected in most cases and affected individuals may have trouble reading or have spots in their field of vision. Later in the course of the disease, the ability to perceive color is affected. Affected individuals may also need more time than normal to adjust from moving between bright and dark environments. Peripheral vision and the ability to see at night or in low light environments are usually unaffected. Stargardt disease is inherited as an autosomal recessive trait.
X-linked retinoschisis is a genetic disorder that affects the specialized light-sensitive tissue at the back of the eye (retina). Specifically, the cells in the center area of the retina (macula) are affected, which causes decreased clarity (acuity) of vision. X-linked retinoschisis may be diagnosed in infancy due to symptoms of squinting or at school age due to decreased clarity of vision. The condition is typically mild until age 40, at which point an individual’s clarity of vision decreases progressively. X-linked retinoschisis is inherited in an X-linked pattern, and almost exclusively occurs in males. In fact, X-linked retinoschisis is the leading cause of macular degeneration in young males. (For more information on this disorder, choose “X-linked retinoschisis” as your search term in the Rare Disease Database.)
Choroideremia is a genetic disorder that causes progressive vision loss. Individuals with choroideremia experience a progressive loss of cells in the light-sensitive tissue at the back of the eye (retina) and in the network of blood vessels in the eye (choroid). Symptoms may begin in early childhood, typically starting with difficulty seeing in low light (night blindness). Later in life, the field of vision becomes progressively narrower (tunnel vision), and progressive decreased clarity (acuity) of vision occurs as well. Choroideremia is inherited in an X-linked pattern, and usually affects males. (For more information on this disorder, choose “Choroideremia” as your search term in the Rare Disease Database.)
Syndromic cone dystrophy is a general term for a cone dystrophy that occurs as part of a larger syndrome. These syndromes include Bardet-Biedl syndrome, Refsum disease, Batten disease, NARP syndrome and spinocerebellar ataxia type 7. These disorders have additional symptoms unrelated to cone dystrophy. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
DIAGNOSIS
A diagnosis of cone dystrophy is made based on identification of characteristic symptoms, a detailed family history, and a thorough clinical evaluation involving ophthalmological exams that measure visual acuity, the ability to perceive color and field of vision. An electroretinogram (ERG) is used to confirm the diagnosis of cone dystrophy.
During an ERG, eye drops are used to numb the eye before placing a special contact lens-electrode on the eye. The patient then watches a set of flashing lights in order to stimulate the retina. Doctors can then measure the electrical signals made by the cone and rod cells. An ERG test is performed twice – once in a bright room and once in a dark room. The test can determine whether cone and rod cells are functioning properly. A weak or absent signal of cone cells indicates cone dystrophy.
STANDARD THERAPIES
Treatment
There is no cure for cone dystrophy. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may include using tinted lenses or dark sunglass in bright environments and magnifying devices to assist in reading and other similar activities.
Genetic counseling is recommended for affected individuals and their families. Genetic counselors help individuals and families assess the chance of inherited disease as well as understand and adapt to its implications. Other treatment is symptomatic and supportive.
CLINICAL TRIALS AND STUDIES
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222TTY: (866) 411-1010Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
REFERENCES
TEXTBOOKSTsang SH, Sharma T. Progressive cone dystrophy and cone-rod dystrophy (XL, AD, and AR). In: Atlas of Inherited Retinal Diseases. Cham, Switzerland: Springer; 2018:53-60.
Heckenlively, John R. Cone Dystrophies and Degenerations. In: Principles and Practice of Clinical Electrophysiology of Vision, JR Heckenlively and GB Arden editors. 2006 MIT Press, Cambridge, MA. pp. 795-802.
Ho AC, Brown GC, McNamara JA. Eds. Retina: Color Atlas & Synopsis of Clinical Ophthalmology. McGraw-Hill Companies, Inc. Columbus, OH. 2003:146-147.
Tasman W, Jaeger EA, ed. Atlas of Clinical Ophthalmology, 2nd ed. Lippincott, Williams & Wilkins. Philadelphia;2001:173-174.
JOURNAL ARTICLES
Sahel JA, Marazova K, Audo I. Clinical characteristics and current therapies for inherited retinal degenerations. Cold Spring Harb Perspect Med. 2014;5(2):a017111.
Kohl S. Genetic causes of hereditary cone and cone-rod dystrophies. Ophthalmologe. 2009;106:109-115.
Holopigian K, Greenstein VC, Seiple W, Hood DC, Carr RE. Rod and cone photoreceptor function in patients with cone dystrophy. Invest Ophthalmol Vis Sci. 2004;45:275-281.