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Complexities in Diagnosing Inherited Retinal Diseases

Explore the overlapping challenges of inherited retinal diseases

The genetic heterogeneity of inherited retinal diseases can make it challenging to reach a specific diagnosis. A single gene may even be associated with multiple phenotypes1-3

Ven diagram with overlapping circles labeled with inherited retinal diseases: CSNB, RP, LCA, Alström, US, CD/CRD, CSNB, BBS, LCA, JBS, LCA, and SLS/NPHP.

*Mapped genetic loci without an identified gene, as of 2019.4

©2021 American Academy of Ophthalmology. Reproduced with permission.

BBS=Bardet-Biedl syndrome; CD=cone dystrophy; CSNB=congenital stationary night blindness; CRD=cone-rod dystrophy; JBS=Joubert syndrome; LCA=Leber congenital amaurosis; NPHP=nephronophthisis; RP=retinitis pigmentosa; SLS=Sjögren-Larsson syndrome; USH=Usher syndrome.

Genetic testing further supports clinical findings and has become the standard for reaching a more precise diagnosis. A more accurate diagnosis helps inform the best course of action for future medical management1,15

Read case studies about overlapping gene variants

The American Academy of Ophthalmology recommends genetic testing for most patients with a suspected inherited retinal disease.

Inherited retinal diseases: signs, symptoms, and prevalence

Disclaimer: All prevalence rates are global estimates and may vary across regions.

Signs & symptoms may include

  • Nyctalopia (earliest symptom)
  • Blind spots merge to produce tunnel vision over time
  • Loss of central vision over time

Age of onset

  • Presents in childhood or adulthood

Estimated prevalence

  • Up to 1 in 3,000

Signs & symptoms may include

  • Males experience earlier and more severe symptoms than females
  • Rapid progression of vision loss, resulting in legal blindness
  • Early nyctalopia

Age of onset

  • Early onset

Estimated prevalence

  • 5%–15% diagnosed with RP

Signs & symptoms may include

  • Partial or total hearing loss and vision loss over time
  • Loss of night vision occurs first
  • Blind spots merge to produce tunnel vision over time
  • Three different clinical types (I, II, and III) with variable symptom severity and presentation

Age of onset

  • Presents at birth (Usher syndrome type I, type II), or by adolescence or adulthood (Usher syndrome type III)

Estimated prevalence

  • Up to 1 in 6,000

Signs & symptoms may include

  • Slow, progressive loss of central vision
  • Nyctalopia
  • Color blindness

Age of onset

  • Presents in late childhood to early adulthood

Estimated prevalence

  • Up to 1 in 8,000

Signs & symptoms may include

  • Decreased visual acuity
  • Photophobia
  • Loss of color vision
  • Scotomas
  • Loss of peripheral vision
  • Legal blindness by mid-adulthood

Age of onset

  • Presents in childhood

Estimated prevalence

  • Up to 1 in 30,000

Signs & symptoms may include

  • Partial or total absence of color vision
  • Can only see black, white, and shades of gray
  • Photophobia
  • Nystagmus
  • Reduced visual acuity
  • Hyperopia

Age of onset

  • Presents at birth or early infancy

Estimated prevalence

  • Up to 1 in 30,000

Signs & symptoms may include

  • Vision loss (at birth to early infancy)
  • Photophobia
  • Nystagmus
  • Hyperopia
  • Keratoconus
  • Franceschetti’s oculo-digital sign (eye poking, pressing, and rubbing)

Age of onset

  • Usually presents at infancy

Estimated prevalence

  • Up to 1 in 33,000

Signs & symptoms may include

  • Progressive atrophy of the outer retina and inner choroid
  • Nyctalopia in early childhood
  • Progressive loss of peripheral visual field and visual acuity
  • All individuals will develop blindness, most commonly in late adulthood

Age of onset

  • Usually presents in early childhood

Estimated prevalence

  • Up to 1 in 50,000

Signs & symptoms may include

  • Nyctalopia
  • Blind spots merge to produce tunnel vision over time
  • Blurred central vision
  • Legally blind by adolescence or early adulthood
  • Renal malformations
  • Obesity
  • Postaxial polydactyly
  • Hypogonadism
  • Developmental delays

Age of onset

  • Ocular symptoms present in first decade of life

Estimated prevalence

  • Up to 1 in 160,000
  • While BBS is one of the rarest inherited retinal diseases, its prevalence may be higher in some geographic regions

Family history alone doesn’t tell the full story

Obtaining a thorough family history can help assess your patient’s risk or identify a likely pattern of inheritance. Although the majority of patients who have no known family history have autosomal recessive disease, some may have dominant disease due to a de novo pathogenic variant. Others may have a dominant disease exhibiting incomplete penetrance. And still there are those who may have no known family history of X-linked disease.1,21,22

of patients with retinitis pigmentosa have no known family history of retinal disease22

Early testing matters

Early genetic testing may allow you to detect genetic variants responsible for inherited retinal diseases sooner.23,24 This enables you and your patients’ care teams to create a more comprehensive plan for the future.20,25

New answers may help your patients move forward in their lives from career and family planning to speaking with family members who may also benefit from genetic testing.20,25

A male doctor and female patient look at a computer screen while the doctor gestures at the screen and talks