Pattern Dystrophies

Pattern dystrophies are inherited in an autosomal dominant fashion and they involve the Retinal Pigment Epithelium (RPE) and the external macular retina. Pattern dystrophies represent a group of disorders that present in midlife with mild visual disturbances in one or both eyes. Since patients present later in life with this condition, they are often misdiagnosed as having Age-Related Macular Degeneration. Inherited pattern macular dystrophies are not a form of AMD, but they do share many important features with ARMD. These patients present with various patterns of yellow, orange or gray pigment deposits in the macular area.

Autosomal Dominant Inheritance has to do with genes and chromosomes. Genes are the basic unit of inheritance. They provide the instructions for growth and development from the single cell of a fertilized egg into the complex structure of a baby. Many continue to provide instructions for the production of proteins needed for bodily functions throughout a person's lifetime. Genes are strung together like beads on a string and packaged into individual chromosomes. Chromosomes come in pairs, with one coming from an individual's mother and the other from the father. One pair of chromosomes is called the sex chromosomes, since they determine the sex of the individual. The other 22 pairs of chromosomes are called autosomes.

Since our chromosomes come in pairs, we have two copies of all of our genes. The two copies in a pair of genes may or may not have the same code. A gene that is expressed regardless of the code in the other gene is said to be dominant. An autosomal dominant gene is one carried on one of the 22 pairs of autosomes. This means that males and females with the gene are equally likely to pass it on to male or female offspring.

A person who has a pattern macular dystrophy has one gene for the pattern dystrophy and one normal gene in one pair of genes. For example, if the father has one gene for the pattern dystrophy and one normal gene and the mother has two normal genes, the mother will always contribute a normal gene from that pair when they have children. There is a 50% chance the father will contribute the pattern dystrophy gene and a 50% chance he will contribute the normal gene.

There can be variation in the expression of a dominant gene even within the same family. In other words, the gene may cause a profound loss of vision for an individual and only a mild to moderate loss for that individual's child. Another phenomenon that is seen with some dominant genes is non-penetrance. This means that there is no detectable evidence that an individual with a dominant gene has the gene. When the gene is non-penetrant, it appears that the gene has skipped a generation. An example of this would be in a family with many people who have pattern dystrophy, including a child and a grandparent, but the intervening parent who has the same dominant gene for pattern dystrophy, has normal vision. Over the past few years, significant progress has been made in the molecular genetics of inherited macular dystrophies. Genes responsible for dominant and recessive Stargardt's macular dystrophy, as well as, Best's disease, have been localized to specific chromosomal regions. The peripherin/RDS gene, when defective, is associated with butterfly-shaped pattern dystrophy.

Based on the pattern of pigment distribution in the macula, this disease has been subdivided into five principle groups:

Group 1: adult-onset foveomacular vitelliform dystrophy.
Group 2: butterfly-shaped pigment dystrophy.
Group 3: reticular dystrophy of the RPE.
Group 4: multifocal pattern dystrophy simulating fundus flavimaculatus.
Group 5: fundus pulverulentus.

Patients with pattern dystrophies may show different patterns between the two eyes. They may even show progression from one pattern to another over several years. Patients can have a pattern dystrophy in just one eye since it may not yet have presented in the fellow eye. The presence of different pattern dystrophies within the same family suggests a common etiologic continuum. Pattern dystrophies of the retinal pigment epithelium, an arrangement of a pattern of dots, lines, or branches, are infrequent fundus abnormalities.

Patients with adult-onset foveomacular vitelliform dystrophy generally present with a solitary yellow subretinal lesion that's symmetric, round and slightly elevated. It is usually about 1/3 to 1 disc diameter in size (the size of the optic nerve that is visible in the retina). There is often a pigmented spot in the center. Initially, the yellow lesion may develop only in one eye. Most of the vitelliform lesions in this condition are small, but the larger ones can look identical to the "sunny-side-up" stage (looks like an egg sunny-side-up) of Best's vitelliform macular dystrophy. These can also look quite similar to bilateral serous detachments of the RPE. In differentiating Best's disease from these adult vitelliform lesions, it is important to remember that the vitelliform lesions in Best's develop in infancy or early childhood. Also, genetic linkage studies have identified Best's disease to a different chromosome. Attempts to identify common genetic linkage between Best's disease and other vitelliform macular dystrophies have been unsuccessful. The prognosis for maintaining good vision is favorable with this type. The elevated foveal lesions generally fade and leave an irregular oval or round area of RPE depigmentation. The lesions generally do not show the sort of disruption and layering of the yellow pigment that is seen with Best's vitelliform lesions. Choroidal neovascularization may occur, but it is rare.

Patients with a butterfly-shaped pattern dystrophy will have gray or yellow pigment in a well-organized pattern.

With reticular dystrophy, the pattern extends into the periphery and the yellow pigment is highly organized, in a manner resembling the knotted configuration of a fishnet or chicken wire.

Those with multifocal pattern dystrophy simulating fundus flavimaculatus develop a pattern of flecks similar to those of Stargardt's disease, but these patients do not show angiographic evidence of a dark choroid suggesting a lipofuscin storage disease. The RPE dystrophy is characterized by an X-shaped yellowish macular lesion and numerus flavimaculatus retinal flecks. The condition is bilateral, has a dominant inheritance, and starts in middle age with a slow-developing macular lesion. Visual functions are often minimally disturbed for two or three decades. The association between flaveomacular vitilliform macular dystrophy and vascularized pigment epithelial detachment (PED), supports the hypothesis that flaveomacular vitilliform macular dystrophy may be a different subgroup of age-related macular degeneration with specific genetic predisposition. Adult onset foveomacular vitelliform dystrophy (AOFVD) is considered a subtype of pattern dystrophy. Onset occurs during middle age, with an accumulation of yellow-gray macular deposits in the deeper retinal layers. Electro-oculograms are mildly subnormal or normal. Genetic studies suggest an autosomal dominant inheritance with variable penetrance.

Patients with fundus pulverulentus display prominent, coarse, "punctiform" mottling of the RPE in the macular area. Further testing might include an electro-oculogram (EOG) and fluorescein angiography. Angiography may show hypofluorescence (under fluorescence) from increased pigmentation or hyperfluorescence (over fluorescence) due to RPE atrophy. Patients will infrequently show evidence of choroidal neovascularization. Pattern dystrophy has been associated with pseudoxanthoma elasticum and myotonic dystrophy. The visual prognosis is favorable. Usually, good visual acuity is maintained in this inherited macular disease. However, acute visual loss can be caused by the ingrowth of subretinal new vessels. Therefore, if visual acuity decreases or metamorphopsia (crooked lines and different sized squares on an Amsler Grid) develops in these patients, careful fluorescein or Indocyanine Green angiography is advisable. Management should include photodocumentation, laser intervention (if there is choroidal neovascularization), and genetic counseling. There should be annual follow-up.

REFERENCES:
Retinal Quiz April 2000 Review of Optometry Mark T. Dunbar, O.D.
Surv Ophthalmol 1995 Jul-Aug;40(1):51-61 Genetic and molecular studies of macular dystrophies: recent developments. Zhang K, Nguyen TH, Crandall A, Donoso LA. Henry and Corinne Bower. Laboratory for Macular Degeneration, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.
Ophtalmologie 1990 Jul-Aug;4(4):372-6 Francois P, Puech B, Turut P. Service d'Exploration Fonctionnelle de la Vision, Lille. Eye 1990;4 ( Pt 1):210-5 Adult vitelliform macular dystrophy. Brecher R, Bird AC. Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye Hospital, London.

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