What Is Variable Expressivity?
Variable expressivity is a biological phenomenon in which people with identical genetic conditions have significant variability in their disease severity, onset, and symptoms. For example, some individuals have severe symptoms that affect their activities of daily living, whereas other individuals see their symptoms as a minor nuisance. Variable expressivity is common in eye conditions such as Best Disease and congenital glaucoma.
Key Takeaways
- Variable expressivity means that people with the same genetic disease can have different disease severity.
- Variable expressivity can cause differences in the age of onset, clinical course, symptoms, and outcomes of the disease.
- Prominent eye diseases that have variable expressivity are congenital glaucoma, Fuchs’ endothelial dystrophy, and Best Disease.
Understanding Variable Expressivity
Variable expressivity describes the phenomenon that for certain hereditary diseases, people with the disease can have different severity of disease. One person may have no symptoms while someone else has severe symptoms, although the genetic mutation is identical in both people. In variable expressivity, the same genotype can cause a wide variety of clinical symptoms across the spectrum.
Incomplete penetrance is the opposite concept of variable expressivity. Incomplete penetrance means that there is absence of clinical disease in people with a known disease-causing genotype. Incomplete penetrance measures the presence or absence of a disease while variable expressivity measures the severity of a disease.
Variable expressivity examples include:
- Different age of disease onset
- Different clinical course of the disease
- Different symptoms
- Different outcome, such as extent of visual impairment
Disorders Related To Variable Expressivity
- Primary Congenital Glaucoma
- Glaucoma is an eye disease that causes degeneration of the optic nerve, and visual field loss. Congenital glaucoma causes blindness in children younger than 3 years old.
- The CYP1B1 gene is implicated in congenital glaucoma. The prognosis for patients with this genetic mutation is variable. Some children may have good vision while others go blind.
- Fuchs’ Endothelial Dystrophy
- TCF4 mutations cause Fuchs’ endothelial dystrophy, a genetic disease that causes slowly progressive cloudy vision from loss of corneal endothelial cells.
- Some people with Fuchs’ dystrophy will have no symptoms, while others will see glare, halos around lights, and have reduced vision.
- Best Disease
- The mutation of the BEST1 gene causes this eye disease, where there is toxic lipofuscin accumulation in the retina. Due to variable expressivity, onset of this disease varies from 3 to 15 years old.
- Leber Hereditary Optic Neuropathy
- Mutations in RPE65 cause this disease, involving blurry central vision in one eye. Although some people with this disease have no systemic involvement, others will also have cardiac issues and muscle weakness.
- X-Linked Retinoschisis
- Mutations in the RS1 gene cause X-linked retinoschisis, loss of central and peripheral vision due to degeneration of the retina. Some people with this disease have poor outcomes due to retinal detachment and vitreous hemorrhage, while others have 20/20 vision throughout their lifetime.
- Duane’s Syndrome
- Duane’s retraction syndrome is a congenital strabismus syndrome that causes eye misalignment from birth. The CHN1 gene is implicated in this disease. Children who are affected may have double vision and permanently reduced vision, whereas other children may only have an eye turn.
