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Sorsby Pseudoinflammatory Fundus Dystrophy

OMIM ID:

autosomal dominant

Sorsby Pseudoinflammatory Fundus Dystrophy

Alternate Names

SFD
hemorrhagic macular dystrophy
Sorsby Fundus Dystrophy

Defective Genes

TIMP3

Clinical Characteristics

Ocular Features

Sorsby Pseudoinflammatroy Fundus Dystrophy is characterized by progressive degeneration of the central macula of the retina with edema, hemorrhages and exudates with pigment changes.  The onset is typically in the second to fourth decade with development of a disciform central macular atrophy with white and yellow spots (not drusen).  This is followed by subretinal neovascular membranes in the majority of patients.  Further degeneration occurs over years and can spread from the center to the periphery of the retina with a corresponding visual field defect.  Night blindness or difficulties adapting to changes in light intensity may be noted before the central macular degeneration occurs.  In histopathologic studies, a subretinal deposit can be observed in Bruchs membrane.

Systemic Features

No general systemic manifestations are associated with Sorsby Pseudoinflammatory Fundus Dystrophy.

Genetics

Inheritance

Sorsby Pseudoinflammatory Fundus Dystrophy is an autosomal dominant disorder, caused by mutations in the TIMP3 gene, located at 22q12.1-q13.2.  Evidence for a separate recessive form (264420) is somewhat refuted by the fact that genotyping found heterozygosity of the TIMP3 mutation in some families.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

In patients with early stages of the disease, a daily dose of 50,000 IU Vitamin A given by mouth has been shown to reverse the symptoms of night blindness.  Treatment with anti-angiogenic agents or steroids has shown improvement in visual acuity in some patients. Patients with decreased vision may find benefit with low vision aids.

Publications

Displaying 1 - 6 of 6

Autosomal recessive Sorsby fundus dystrophy revisited: molecular evidence for dominant inheritance

PubMedID: 8981947

Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby’s fundus dystrophy

PubMedID: 7894485

Night blindness in Sorsby’s fundus dystrophy reversed by vitamin A

PubMedID: 7550309

Sorsby fundus dystrophy – A review of pathology and disease mechanisms

PubMedID: 28847738

Sorsby’s Fundus Dystrophy

PubMedID: 2695876

The genetics of inherited macular dystrophies

PubMedID: 12960208