1. Home
  2. Knowledge Base
  3. Pattern dystrophy: for professionals
Searching...

Pattern dystrophy: for professionals

Overview

PrevalenceEstimated over 300,000 in greater Europe
InheritanceAutosomal dominant
Genes Involved (OMIM No.)PRPH2 (#179605), BEST1 (#607854), ABCA4 (#601691)
Symptoms– Mildly impaired central or paracentral vision – Distortion in vision
Ocular Features– Macular pigmentary changes – Yellow-white subretinal deposits – Vitelliform lesions – Severe outer retinal atrophy (in advanced cases)
Systemic featuresMay be associated with multisystemic syndromes such as maternally inherited diabetes and deafness (MIDD) or pseudoxanthoma elasticum (PXE)
Key InvestigationsOphthalmic: – Fundoscopy – Optical coherence tomography (OCT) – Fundus autofluorescence (FAF) – Electrophysiological testing (ERG, EOG)
Molecular DiagnosisWhole genome sequencing with panel based tests
ManagementOcular: – Regular ophthalmic monitoring – Optical aids and low vision assessments – Intravitreal injections for choroidal neovascularisation
Therapies under ResearchOngoing studies on gene therapy

Jump to top

Clinical phenotype

Pattern dystrophies of the retinal pigment epithelium (RPE) are a genetically and phenotypically diverse group of disorders primarily affecting the macula and visual function. They usually present in adulthood and are characterised by macular abnormalities visible on fundus examination. Common findings include pigmentary changes and yellow-white retinal lesions, often more apparent on fundus autofluorescence imaging than on clinical examination or colour fundus photography.1,2

Presenting features

Ocular

  • Asymptomatic Individuals: Often, pattern dystrophies are detected during routine eye examinations.3,4
  • Symptomatic Individuals: Present with mildly impaired central or paracentral vision and distortion. In severe cases, extensive outer retinal atrophy can lead to significant visual impairment.5,6

Systemic

Patten dystrophies can often be associated with syndromic conditions as follows7:

  • MIDD/MELAS
    • Gene: MTTL1 (Mitochondrial transfer RNA for leucine)Ocular features: Parafoveal areas of atrophy, irregular autofluorescence in the posterior pole, possible ptosis or ophthalmoplegia
    • Systemic features:
      • MIDD: Diabetes, deafness, ptosis, hearing problems, cardiac conduction abnormalities, nephropathy
      • MELAS: Headaches, vomiting, convulsions, deafness, myopathy, neuropathy
  • Pseudoxanthoma Elasticum (PXE)
    • Gene: ABCC6 (ATP-binding cassette C6)
    • Ocular features: Angioid streaks, irregular autofluorescence, CNV, subretinal drusenoid deposits, RPE mottling (peau d’orange), subretinal fluid, comet lesions, hyper-reflective Bruch’s membrane on OCT
    • Systemic features: Abnormal mineralisation of skin and organs, arterial calcification, coronary artery fibrosis, gastrointestinal bleeds
  • Myotonic Dystrophy
    • Gene: DMPK (Dystrophia myotonica protein kinase)
    • Ocular features: Butterfly-shaped pigment dystrophy, reticular pattern dystrophy, peripheral atrophic polygonal-shaped retinal changes, cataracts
    • Systemic features: Myotonia, muscular dystrophy, hypogonadism, cardiac conduction abnormalities
  • McArdle Disease
    • Gene: PYGM (Muscle isoform of glycogen phosphorylase)
    • Ocular features: Outer retinal deposits, areas of atrophy (in some cases)
    • Systemic features: Exercise intolerance, rhabdomyolysis
  • Kjellin Syndrome
    • Gene: ZFYVE26 (Zinc finger FYVE domain-containing protein 26)
    • Ocular features: Central retinal degeneration, flecks (carriers might have flecks without systemic features), pigmentary abnormalities and atrophy
    • Systemic features: Progressive spastic paraplegia, neurologic dysfunction, thin corpus callosum
  • SPG11 (Spastic Paraplegia 11)
    • Gene: SPG11 (Spatacsin)
    • Ocular features: Central retinal degeneration, pigmentary abnormalities and atrophy
    • Systemic features: Progressive spastic paraplegia, neurologic dysfunction, thin corpus callosum

Fundal appearance

  • Macular pigmentary changes: Both eyes typically show pigmentary abnormalities, which can be semi-linear and radiate from the foveal centre. Based on the pattern of the pigment distribution they have been classified into 5 prominent categories8:
    • Adult-Onset Foveomacular Vitelliform Dystrophy (AOFVD)
      • Characterised by yellow, egg-yolk-like lesions in the fovea.
      • Lesions typically measure 0.5 to 1 disc diameter.
      • May present as solitary or multifocal.
    • Butterfly-Shaped Pigment Dystrophy
      • Pigmentation resembles the shape of a butterfly.
      • Pigmentary changes are found in the foveal or parafoveal regions.
      • Often symmetrical between both eyes.
    • Reticular Dystrophy
      • Net-like or fishnet pattern of pigmentation.
      • Found throughout the posterior pole, especially near the macula.
      • Pigment tends to be brown or black.
    • Multifocal Pattern Dystrophy Simulating Fundus Flavimaculatus
      • Multiple yellow-white, pisciform lesions scattered throughout the posterior pole.
      • Lesions may resemble those seen in Stargardt disease but without central vision loss in early stages.
      • Lesions often have fleck-like appearance.
    • Fundus Pulverulentus
      • Characterised by numerous, tiny, dust-like pigment clumps.
      • Distributed diffusely across the fundus, including the macula.
      • Pigment clumps may be yellow or brown.
  • Yellow-white retinal deposits: These are common and are more noticeable during an eye examination.
  • Vitelliform lesions: Central yellow-white subretinal lesions may be seen, particularly in cases associated with BEST1 mutations (Best disease).
  • Atrophic areas: These can be multifocal with associated areas of visual loss.

Jump to top

Genetics

  1. Gene: PRPH2 (6p21.2)
    • OMIM No.: #179605
    • Inheritance Pattern: Autosomal dominant
    • Effect: Mutations in PRPH2, which encodes peripherin-2, a structural protein in photoreceptor cells, are associated with a wide range of phenotypes including pattern dystrophy, central areolar choroidal dystrophy, cone-rod dystrophy, and rod-cone dystrophy. Missense mutations often lead to dominant negative effects resulting in cone-dominated pathologies, while other mutations can result in rod-dominated conditions.7,9,10
  2. Gene: BEST1 (11q12.3)
    • OMIM No.: #607854
    • Inheritance Pattern: Autosomal dominant
    • Effect: Mutations in BEST1, which encodes bestrophin-1, a protein involved in the maintenance of the RPE and ion transport, are primarily associated with Best disease. Certain variants, such as c.728C>T (p.Ala243Val), are linked to adult-onset pattern dystrophy phenotypes. These mutations lead to subnormal EOG LP ratios and progressive macular atrophy.
  3. Gene: ABCA4 (1p22.1)
    • OMIM No.: #601691
    • Inheritance Pattern: Autosomal recessive
    • Effect: ABCA4 mutations, known for their role in Stargardt disease, are also implicated in pattern dystrophy. The ABCA4 gene encodes an ATP-binding cassette transporter involved in the visual cycle. Mutations disrupt the clearance of retinaldehyde, leading to toxic accumulation and photoreceptor degeneration.
  4. Gene: IMPG1 (6q14.1)
    • OMIM No.: #613085
    • Inheritance Pattern: Autosomal dominant and autosomal recessive
    • Effect: Mutations in IMPG1, encoding interphotoreceptor matrix proteoglycan 1, lead to various phenotypes including pattern dystrophy and rod-cone dystrophy. These mutations affect the interphotoreceptor matrix, which is crucial for photoreceptor function and survival.
  5. Gene: IMPG2 (3q12.3)
    • OMIM No.: #607056
    • Inheritance Pattern: Autosomal dominant and autosomal recessive
    • Effect: Similar to IMPG1, mutations in IMPG2 disrupt the interphotoreceptor matrix, leading to macular pattern dystrophy and rod-cone dystrophy. The resulting phenotype depends on the nature of the mutation and its impact on protein function.
  6. Additional Genes:
    • OTX2 (14q22.3): Associated with autosomal dominant pattern dystrophy, OTX2 mutations can also lead to developmental anomalies due to its role in eye and brain development.
    • RP2 (Xp11.3): Primarily associated with X-linked retinitis pigmentosa, RP2 mutations can occasionally present with a pattern dystrophy phenotype.
    • HTRA1 (10q26.13): A single-nucleotide polymorphism (rs11200638) in HTRA1 has been linked to late adulthood onset pattern dystrophy.

Further information about each gene can be found on OMIM and Medline Plus.

Jump to top

Key investigations

Ocular

Often patients are asymptomatic and abnormalities are picked up incidentally at opticians.

  1. Optical Coherence Tomography (OCT)
    • Outer retina and RPE abnormalities: OCT frequently shows hyper-reflective material deposition and areas of loss/disruption of the outer retinal layers.11
    • Retinal thinning: Progressive thinning of the retinal nerve fibre and macular ganglion cell layers may be observed.
    • Vitelliform lesions: Hyper-reflective material accumulation beneath the retina can be visualised.
    • Subretinal fluid: May be present, indicating potential choroidal neovascularisation, especially in conditions like PXE.
  2. Fundus autofluorescence (FAF)
    • Hyper- and Hypoautofluorescence: Specific patterns such as multifocal, reticular, or semi-linear areas of hyper- and hypoautofluorescence are typical.12,13
    • Outer retinal deposits: These are often more evident on FAF than on clinical examination or colour fundus photography.
    • Atrophic changes: Areas of hypoautofluorescence correspond to regions of RPE atrophy.
  3. Electroretinogram
    • Pattern ERG: Evaluates macular cone-driven retinal function. The results vary; in cases with mild pigmentary changes, the pattern ERG may be normal, but it is often subnormal or undetectable in cases with significant central retinal atrophy.
    • Full-field ERG: Generally within normal limits as it evaluates the generalised rod and cone system function. This helps differentiate pattern dystrophies from more diffuse retinal diseases.
    • Electro-oculogram (EOG): The LP ratio, which assesses the health of the RPE, may be subnormal in some cases. For example, in BEST1-associated vitelliform macular dystrophy, the LP ratio is often profoundly subnormal even when fundal changes are minimal.14
  4. Visual field testing
    • Central scotomas: Central or paracentral scotomas are common, reflecting areas of retinal damage.
    • Peripheral field involvement: There can be variable involvement of the peripheral visual fields, particularly in more advanced stages.1
  5. Colour vision testing
    • Reduced colour discrimination: Patients often exhibit significant deficits in colour vision, which corresponds with the degree of macular involvement.
  6. Genetic Testing
    • Panel-based Tests: Screening for known pattern dystrophy-associated genes such as PRPH2, BEST1, ABCA4, IMPG1, and IMPG2.
    • Exome or Genome Sequencing: Useful for detecting mutations in less commonly implicated genes and for cases with atypical presentations.

Jump to top

Diagnosis

A comprehensive diagnosis of pattern dystrophy involves integrating clinical features and genetic testing results.

Jump to top

Differential Diagnoses

Differential diagnoses include other syndromes which can present with pattern dystrophies as above e.g. MIDD, PXE, etc. Other differentials include age related macula degeneration, Best disease, Central serous chorioretinopathy etc.

Jump to top

Management

The management of pattern dystrophy focuses on monitoring disease progression and providing supportive care.

Ocular

  1. Regular Monitoring: Routine follow-ups to monitor disease progression.
  2. Low vision aids: Supportive measures including low vision aids.
  3. Anti-VEGF Therapy: Intravitreal injections for cases complicated by choroidal neovascularisation. Treatment protocols vary and should be tailored to the individual patient.15

Family management and counselling

Pierson syndrome is inherited in an autosomal recessive manner. Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Genetic counsellors and Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients and their parents in clinic. They provide emotional and practical support to help patients and parents deal with the diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist centre

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research.

Jump to top

Current research

  1. Gene therapy
    • Gene therapy aims to correct the underlying genetic defects responsible for pattern dystrophies. This approach involves introducing functional copies of the mutated gene into retinal cells to restore normal function.
      • PRPH2 Gene Therapy: Research is ongoing to develop gene therapies targeting mutations in the PRPH2 gene, which is implicated in various pattern dystrophies. These therapies aim to deliver functional PRPH2 genes to retinal cells to restore the structural integrity of photoreceptor cells.
  2. Anti-VEGF Therapy
    • Anti-VEGF (vascular endothelial growth factor) therapy is used to manage choroidal neovascularisation (CNV) associated with some pattern dystrophies. This therapy helps to reduce new blood vessel formation and associated vision loss.
      • Intravitreal Injections: Patients with pattern dystrophies complicated by CNV may receive intravitreal injections of anti-VEGF agents. Research is ongoing to determine optimal dosing regimens and long-term efficacy in this patient population.
  3. Genetic Testing and Precision Medicine
    • Advances in genetic testing are enabling more precise diagnosis and personalised treatment plans for patients with pattern dystrophies.
      • Exome and Genome Sequencing: Comprehensive genetic testing panels are being used to identify causative mutations in patients with pattern dystrophies. This information is critical for developing personalised treatment strategies and enrolling patients in appropriate clinical trials.

Jump to top

Further information and support

Jump to top

References

  1. Ahmed H, Sierpina DI, Khazaeni L. Retinal Pattern Dystrophy. [Updated 2023 Jul 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582129/
  2. Deutman AF, van Blommestein JD, Henkes HE, Waardenburg PJ, Solleveld-van Driest E. Butterfly-shaped pigment dystrophy of the fovea. Arch Ophthalmol. 1970 May;83(5):558-69.
  3. Kim RY, Dollfus H, Keen TJ, Fitzke FW, Arden GB, Bhattacharya SS, Bird AC. Autosomal dominant pattern dystrophy of the retina associated with a 4-base pair insertion at codon 140 in the peripherin/RDS gene. Arch Ophthalmol. 1995 Apr;113(4):451-5.
  4. Weleber RG, Carr RE, Murphey WH, et al. Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene. Arch Ophthalmol. 1993;111:1531-1542.
  5. Yang Z, Li Y, Jiang L, Karan G, Moshfeghi D, O’Connor S, Li X, Yu Z, Lewis H, Zack D, Jacobson S, Zhang K. A novel RDS/peripherin gene mutation associated with diverse macular phenotypes. Ophthalmic Genet. 2004 Jun;25(2):133-45.
  6. Francis PJ, Schultz DW, Gregory AM, Schain MB, Barra R, Majewski J, Ott J, Acott T, Weleber RG, Klein ML. Genetic and phenotypic heterogeneity in pattern dystrophy. Br J Ophthalmol. 2005 Sep;89(9):1115-9.
  7. Black GC, Ashworth JL, Sergouniotis PI, editors. Clinical ophthalmic genetics and genomics. Academic Press; 2022 Jan 18.
  8. Gass JMD. Stereoscopic Atlas Of Macular Disease. Philadelphia, Pa: Elsivier; 1997.
  9. Zhang K, Garibaldi DC, Li Y, et al. Butterfly-Shaped Pattern Dystrophy: A Genetic, Clinical, and Histopathololgical report. Ophthalmic Mol Genet. 2002;120:485-490.
  10. Nicholas BE, Sheffield VC, Vanderburgh K, et al. Butterfly-Shaped Pigment Dystrophy of the Fovea Caused by a point Mutation in codon 167 of the RDS gene. Nat Genet. 1993;3:202-207.
  11. Benhamou N, Souied EH, Zolf R, et al. Adult-onset foveomacular vitelliform dystrophy: a study by optical coherence tomography. Am J Ophthalmol. 2003;135:362-367.
  12. Parodi MB, Iacono P, Pedio M, et al. Autofluorescence in adult-onset foveomacular vitelliform dystrophy. Retina. 2008;28:801-807.
  13. Furino C, Boscia F, Cardascia N, et al. Fundus autofluorescence, optical coherence tomography and visual acuity in adult-onset foveomacular dystrophy. Ophthalmologica. 2008;222:240-244.
  14. Theischen M, Schilling H, Steinhorst UH. EOG in adult vitelliform macular degeneration, butterfly-shaped pattern dystrophy and Best disease. Ophthalmologe. 1997;94:230-233.
  15. Empeslidis T, Vardarinos A, Deane J, Banerjee S. Intravitreal Ranibizumab in the Treatment of Butterfly-Shaped Pattern Dystrophy Associated with Choroidal Neovascularization: A Case Report. Case Rep Ophthalmol. 2012;3(1):77-82. doi: 10.1159/000336987.

Jump to top

Updated on June 3, 2024
Was this article helpful?
Yes No