macular dystrophy

Pigmented Paravenous Chorioretinal Atrophy

Clinical Characteristics
Ocular Features: 

This is a rare type of pigmentary retinopathy with few symptoms in many patients.  Pigment clumps in the form of bone spicules in a paravenous distribution appear as young as 1 year of age and may be present congenitally.  The pigment may begin peripherally and is often segmental but eventually progresses centrally along with chorioretinal atrophy involving the majority of the fundus.  For unknown reasons, males are more severely affected than females.  In one family the retinal changes were associated with hyperopia, esotropia and vitreous degeneration (cells and liquefaction).  There is considerable variation in expressivity among patients and the vision and fundus pigmentation can be highly asymmetrical in the two eyes.  ERG abnormalities likewise vary widely with decreased photopic responses in some individuals and complete lack of both scotopic and photopic responses in severely affected eyes.  Decreased night vision is not a symptom.

This is generally considered to be a stationary condition but long term follow up reveals progression of pigmentary changes, chorioretinal atrophy and increasing constriction of the peripheral visual field.  Symptoms of decreased vision may be noted as early as 3 months of age.  Some patients retain vision of 20/20 or 20/30 into midlife whereas others in the first decade already have count fingers vision.  Likewise the size of the visual field varies widely and is not correlated with age.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is an autosomal dominant disorder caused by heterozygous mutations in the crumbs homolog 1 (CRB1) gene (1q31.3).

CRB1 mutations have been identified in other retinal disorders including nanophthalmos with retinitis pigmentosa, pigmented paravenous chorioretinal atrophy (172870), retinitis pigmentosa-12 (600105), and Leber congenital amaurosis 8 (613835).  No consistent retinal phenotype has been found, however.  There is often marked asymmetry between the two eyes and the rate of visual loss varies widely.  Most individuals have some patchy areas of hypoautofluorescence in the posterior pole with variable amounts of pigmentary anomalies from mild speckling to frank bone spicule formation.

   

 

   

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment is available although low vision aids are likely to be helpful in selected patients.

References
Article Title: 

Macular Edema, Autosomal Dominant Cystoid

Clinical Characteristics
Ocular Features: 

Only a few families have been reported.  The macular edema can be traced to retinal capillary leakage throughout the posterior pole as revealed by fluorescein angiography.  Scattered exudates and nerve fiber layer hemorrhages are sometimes seen.  Hyperopia and strabismus are often present as well.  Veils, strands, and white punctate deposits in the vitreous have been described.  Wrinkling of the internal limiting membrane may be present.  The ERG is normal except for elevated rod dark adaptation thresholds.  Light/dark ratios are abnormal on EOG testing and mild dyschromatopsia can be demonstrated.  Patients usually notice problems with their visual acuity in the second decade of life and it can drop to 20/200 at this time with progression to 2/120 - 2/200 in older individuals.  In later stages of the disease a central zone of beaten bronze macular atrophy can be seen.  Surrounding this central atrophy is often an area with pigmentary changes resembling retinitis pigmentosa which can extend into the periphery.

This would seem to be a unique disorder in spite of some similarities to retinitis pigmentosa in which macular cysts are often seen.  The clinical course is distinctly different and the presence of vitreous deposits and hyperopia also can be used as arguments for its separateness.  Molecular DNA evidence showing lack of allelism (Vida infra) is, of course the strongest evidence.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This autosomal dominant form of progressive macular dystrophy is linked to a locus at 7p21-p15.  The mutation is close to the RP9 locus causing one type of retinitis pigmentosa but linkage analysis shows the two disorders to be non-allelic.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No specific treatment is available for the macular disease but low vision aids are likely useful, at least early in the disease.

References
Article Title: 

Macular Dystrophy, Fenestrated Type

Clinical Characteristics
Ocular Features: 

The earliest fundus findings consisting of a yellowish refractile sheen (about 1 disc diameter in size) with red fenestrations in the central macula were found in a 4 year old.  Changes in macular pigmentation were noted at the age of 16 years.  Visual acuity remains normal.  By the third decade of life an annular zone of hypopigmentation could be seen around the sheen and this gradually enlarged.  The sheen seemed to emanate below the retinal vessels but anterior to the RPE.  At the center a ‘bull’s eye’ pattern of hyperpigmentation appeared.  By the 6th decade of life paracentral scotomas were present causing some visual disturbance.  Fluorescein angiography reveals no abnormalities in the sensory retina or retinal vasculature but an annular zone of window defects around the ‘bull’s eye’ can be seen.  The scotopic ERG can be normal while the amplitudes of the photopic ERG may show a mild reduction in amplitude and the EOG light-dark ratio can also be slightly reduced.  Mild red-green color deficits can be demonstrated.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

No locus or mutation has been identified but the transmission pattern is compatible with autosomal dominant inheritance in the two reported families.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Macular Dystrophy, Occult

Clinical Characteristics
Ocular Features: 

There is considerable clinical heterogeneity in this disorder.  Reduced vision may cause symptoms beginning during adolescence but some individuals may have good vision until the 6th decade or even later.  Even those who complain of changes in acuity may still have 20/20 to 20/25 vision but it may also be much worse, in the range of count fingers.  There can be considerable asymmetry in acuity between the two eyes but there is little known about the rate of vision loss.  Mild dyschromatopsia is often present with deficits in both red-green and red-green discrimination but total color blindness has also been reported.  Full field ERGs usually show no rod or cone deficits.  However, multifocal ERG changes suggest dysfunction of the cones in the macula.  Spectral-domain optical coherence tomography can reveal disruptive changes at the photoreceptor inner/outer segment line and in cone outer segment tips.  Disruption of the external limiting membrane and decreased foveal thickness have also been reported.  The retina appears normal to clinical examination even in advanced stages of disease and fluorescein angiography likewise shows no abnormalities.

Systemic Features: 

No systemic disease has been repoted in this condition.

Genetics

This is an autosomal dominant condition resulting from heterozygous mutations in RP1L1 (8p23.1).  A significant number of sporadic cases occur, however, which suggests new mutations are relatively common or that there is etiologic heterogeneity.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

Optic Nerve Edema, Splenomegaly, Cytopenias

Clinical Characteristics
Ocular Features: 

Persistent optic nerve edema is eventually followed by some degree of optic atrophy.  The nerve edema may be seen early in the first decade of life and is not associated with increased lumbar puncture pressure.  Peripapillary hemorrhages may be seen.  Visual acuity may decrease somewhat by the end of the first decade of life and becomes functionally significant in early adolescence and may be reduced to counting fingers.  The ERG, which shows minimal dysfunction early, eventually appears nearly flat without photopic or scotopic responses.  The retinal vessels become markedly attenuated and the macula may be mildly edematous and show pigmentary changes.  Pigment clumping is not seen.  Visual fields show a central or cecocentral scotoma, enlargement of the blind spot, and eventually severe peripheral constriction.  The vitreous and aqueous humor sometimes have an increased number of cells.   Lenticular opacities requiring cataract surgery has been reported.  One patient developed a phacomorphic angle closure attack at the age of 19 years.

Systemic Features: 

Splenomegaly is a consistent sign and is usually present in the first decade of life but histology shows primarily cellular congestion of the red pulp cords.  Bone marrow biopsies show mild erythroid hyperplasia. Peripheral blood counts show mild neutropenia and thrombocytopenia.  Occasional atypical lymphocytes may be seen.  Patients often complain of mildly to moderately severe migraine headaches.  Urticaria and anhidrosis are common features.

Genetics

Only a single report of this condition has been published.  A mother and two daughters (half sisters) had the symptoms described here and this is the basis for consideration of autosomal dominant inheritance.  Nothing is known regarding the etiology or the mechanism of disease.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Topical, intravitreal, oral, and subtenon application of steroids apparently have no impact on the progression of the intraocular disease.  Cataracts may need to be removed.

References
Article Title: 

An inherited disorder with splenomegaly, cytopenias, and vision loss

Tantravahi SK, Williams LB, Digre KB, Creel DJ, Smock KJ, Deangelis MM, Clayton FC, Vitale AT, Rodgers GM. An inherited disorder with splenomegaly, cytopenias, and vision loss. Am J Med Genet A. 2012 Mar;158A(3):475-81. doi: 10.1002/ajmg.a.34437. Epub 2012 Feb 3.

PubMed ID: 
22307799

Heimler Syndrome 2

Clinical Characteristics
Ocular Features: 

Several cases have been reported with macular dystrophy and 'salt-and-pepper' mottling of the RPE extending to the midperiphery with foveal sparing.  Autofluorescence with hyper- and hypo-autofluorescent dots has been observed in the mottled areas of the RPE.  Spectral domain OCT has shown loss of the inner/outer segment boundary with RPE thinning and multiple retinal cysts but the ERG does not show rod-cone dysfunction. Visual acuity and the ocular fundus were normal in one patient until the age of 29 years when her vision dropped to 20/200 in one eye and 20/40 in the other.

Systemic Features: 

Primary dentition may be normal but secondary teeth have enamel hypoplasia (amelogenesis imperfecta).  The nails have Beau lines (transverse ridges) and leukonychia (white spots).  Severe sensorineural hearing loss develops sometime in the first year or two of life and it may be unilateral. At least one patient was documented to have had normal audiological test results until the age of 3 years.

Psychomotor development is normal at least until sensory deprivation occurs.

Genetics

This is a rare syndrome of ectodermally derived tissue which results from compound heterozygous mutations in the PEX6 gene (6p21.1).  A pair of monozygotic twin girls with this syndrome has been reported.  Parents are phenotypically normal.  No instance of parent-to-child transmission has been noted and it seems likely that this is an autosomal recessive disorder.

Another form of Heimler syndrome (234580) but with compound heterozygous mutations in the PEX1 gene (7q21.2) has been reported.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

One patient has been treated with carbonic anhydrase inhibitors with apparent stabilization of vision.  Low vision aids and assistive hearing devices are likely of benefit for at least some patients.

References
Article Title: 

Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Smith CE, Poulter JA, Levin AV, Capasso JE, Price S, Ben-Yosef T, Sharony R, Newman WG, Shore RC, Brookes SJ, Mighell AJ, Inglehearn CF. Spectrum of PEX1 and PEX6 variants in Heimler syndrome. Eur J Hum Genet. 2016 Nov;24(11):1565-1571.

PubMed ID: 
27302843

Macular dystrophy in Heimler syndrome

Lima LH, Barbazetto IA, Chen R, Yannuzzi LA, Tsang SH, Spaide RF. Macular dystrophy in Heimler syndrome. Ophthalmic Genet. 2011 Jun;32(2):97-100.

PubMed ID: 
21366429

Choroidal Dystrophy, Central Areolar 1

Clinical Characteristics
Ocular Features: 

The primary feature of this form of macular dystrophy is atrophy of the RPE and choriocapillaris centralized to the macula.  In early stages among young patients in the second decade of life, some pigment changes are seen in the parafoveal area.  Later, the central macula develops hypopigmentation followed by atrophy of the choriocapillaris.  The area is usually sharply defined but fluorescein angiography often shows multiple window defects beyond the edges.  The same region often has speckled autofluorescence.  Secondary dysfunction of the photoreceptors in this area leads to some mild degree of vision loss in adults between the ages of 30 and 60 years but this progressive disease may eventually result in legal blindness.  The ERG demonstrates a cone dystrophy. The rate of disease progression is highly variable.  Visual acuity varies considerably as does the appearance of the macula.  Older individuals may be misdiagnosed as having age-related macular degeneration. 

Systemic Features: 

There is no associated systemic disease. 

Genetics

CACD1 is caused by a hterozygous mutations in GUCY2D gene localized to 17p13.  One large three generation Irish family has been reported.

For a somewhat similar disorder see choroidal dystrophy, central areolar 2 (613105).

CACD is a genetically heterogeneous disorder with mutations in several genes responsible.  The majority of patients have one of several mutations in the PRPH2 gene (6p21.1-cen) and the inheritance pattern seems to be autosomal recessive (CACD2).  However, other family trees in which mutations in PRPH2 were excluded suggest autosomal dominant inheritance (CACD3; 613144) suggesting genetic heterogeneity such as the CACD1 condition described here.   

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment of the macular disease.  However, some patients can benefit from low vision aids. 

References
Article Title: 

Central areolar choroidal dystrophy

Boon CJ, Klevering BJ, Cremers FP, Zonneveld-Vrieling MN, Theelen T, Den Hollander AI, Hoyng CB. Central areolar choroidal dystrophy. Ophthalmology. 2009 Apr;116(4):771-82, 782.e1.

PubMed ID: 
19243827

Macular Dystrophy, Patterned 1

Clinical Characteristics
Ocular Features: 

Patterned dystrophies of the macula are clinically heterogeneous.  It is common for different patterns to be seen among multiple members of a single family.  They can also be different in the two eyes of the same individual.  RPE changes can often be seen in the second decade of life but visual disturbances may not be noted until a decade or two later.  The process is progressive and eventually macular function is severely depressed with vision in the range of 20/200.  The pigmentary retinopathy occurs at the level of the RPE with the typical appearance of pigment but sometimes an accumulation of white or yellowish deposits is present.  The pattern of changes may appear in a configuration resembling the wings of a butterfly, hence the name.  However, vitelliform-like lesions have also been reported.  Paracentral tritan color defects have been described.

Subfoveal choroidal neovascularization can occur.

While the ERG may show some diffuse photoreceptor dysfunction in the presence of normal vision, there is little to suggest a primary rod or cone abnormality. Dark adaptation is normal.  Visual fields can reveal a small central scotoma and fluorescein angiography often shows window defects in the posterior pole. 

Systemic Features: 

Simple patterned macular dystrophy is not associated with systemic disease. 

Genetics

Pattern macular dystrophies are usually inherited as autosomal dominant conditions.  Several mutations in separate genes have been linked to these disorders suggesting that this group is genetically as well as clinically heterogeneous. 

Some families have mutations in the photoreceptor peripherin gene (PRPH2) at 6p21.1-cen (169150) whose gene product is active in the retina. It is important to the integrity and stability of the structures that contain light-sensitive pigments (e.g., photoreceptors). More than 100 mutations have been identified. The resultant phenotype can be highly variable, even within members of the same family but most affected individuals have some degree of pigmentary retinopathy within the macula or throughout the posterior pole.  The altered gene product coded by mutations in PRPH2 often leads to symptoms beginning in midlife as a result of the slow degeneration of photoreceptors. This database contains at least 11 disorders in which PRPH2 mutations have been found.

A locus at 5q21.2-q33.2 containing heterozygous CTNNA1 mutations has been linked to a pattern dystrophy (Macular Dystrophy, Patterned 2) (608970). 

As many as 25% of patients with myotonic dystrophy 1 (160900) and myotonic dystrophy 2 (602668) have a patterned pigmentary maculopathy.

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for the macular disease but low vision aids should be considered for appropriate individuals. 

Surveillance is useful for the detection of choroidal neovascularization and prompt treatment with ranibizumab injections can be useful in the elimination of this complication.

References
Article Title: 

Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections

Vaclavik V, Tran HV, Gaillard MC, Schorderet DF, Munier FL. Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections. Retina. 2012 Oct;32(9):1942-9.

PubMed ID: 
22466463

Jalili Syndrome

Clinical Characteristics
Ocular Features: 

Symptoms of photophobia and reduced vision are present in the first years of life.  Pendular nystagmus is common.  Color vision is defective and is characterized by some as a form of achromatopsia, perhaps better described as dyschromatopsia.  Reduced night vision is noted by the end of the first decade of life.  OCT reveals reduced foveal and retinal thickness.  The macula appears atrophic with pigment mottling and the peripheral retina can resemble retinitis pigmentosa with bone spicule pigment changes.  Retinal vessels may be narrow.  The ERG shows reduced responses in both photopic and scotopic recordings.  This form of rod-cone dystrophy is progressive with central acuity decreasing with age. 

Systemic Features: 

The teeth are abnormally shaped and discolored from birth.  The amelogenesis imperfecta consists of hypoplasia and hypomineralization that is present in both deciduous and permanent teeth.  Tooth enamel is mineralized only to 50% of normal and is similar to that of dentine. 

Genetics

This is an autosomal recessive condition caused by mutations in the CNNM4 gene at 2q11.2. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the ocular condition but red-tinted lenses and low vision aids may be helpful.  The teeth require dental repair. 

References
Article Title: 

Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta

Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, Bloch-Zupan A, Carlos R, Carr IM, Downey LM, Blain KM, Mansfield DC, Shahrabi M, Heidari M, Aref P, Abbasi M, Michaelides M, Moore AT, Kirkham J, Inglehearn CF. Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet. 2009 Feb;84(2):266-73.

PubMed ID: 
19200525

EEM Syndrome

Clinical Characteristics
Ocular Features: 

Granular pigmentation and a grayish coloration of the retina may be present.  The peripheral retina usually appears normal but the posterior pole and macula have pigmentary changes consisting of clumping and geographic atrophy.  Fluorescein angiography shows patchy areas of hyperfluorescence.  Patients in their 30s have been reported to have normal ERGs in one study.  Reduced acuity can be noted in the first decade but progression is slow.  Acuity levels in the 20/200 range may be seen in the fourth decade of life. 

Systemic Features: 

Ectodermal dysplasia with ectrodactyly and syndactyly are prominent features of this syndrome.  Hypotrichosis of the scalp, eyebrows and eyelashes is often seen.  Partial anodontia and diastema are also features.  Syndactyly of the toes is present more frequently than found among the fingers. 

Genetics

This is an autosomal recessive disorder resulting from mutations in the CDH3 gene (16q22.1).

EEM syndrome is allelic to the Hypotrichosis with Macular Dystrophy syndrome (601553).  However, the latter lacks the dental, limb, and digital anomalies as well as the hypotrichosis of eyebrows and eyelashes.  

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for this disease. 

References
Article Title: 

Pages

Subscribe to RSS - macular dystrophy