Other Organ System Disorders
Most retinopathies associated with other organ systems are rare and genetic, and clinicians may find the Online Mendelian Inheritance in Man website (www.omim.org) useful in recognizing them.
Several forms of congenital renal disease may be associated with retinal degeneration. Familial juvenile nephronophthisis is one of the family of renal-retinal dysplasia (and ciliopathy) characterized by autosomal recessive inheritance and childhood onset of end-stage renal disease. Individuals with Joubert syndrome have cerebellar malformation (a characteristic “molar tooth” deformity that can be observed on magnetic resonance imaging of the brain) and may also have associated chorioretinal coloboma. Patients with Bardet-Biedl syndrome commonly have urethral reflux with pyelonephritis and kidney damage, whereas patients with Alström syndrome, another retinal ciliopathy, may demonstrate obesity, short stature, and cardiomyopathy in addition to renal disease. Jeune syndrome is a retinal ciliopathy that is complicated by cystic kidney disease and asphyxiating thoracic dystrophy.
Patients with Alagille syndrome present with hepatorenal abnormalities including cholestatic jaundice and have several characteristic ocular findings, including posterior embryotoxin and pigmentary retinopathy, that can have a peripapillary and macular predilection.
Familial adenomatous polyposis (FAP, also known as Gardner syndrome) is associated with pigmented lesions that are similar to those found in congenital hypertrophy of the RPE. However, the lesions in FAP are smaller, ovoid, more variegated, and typically multiple and bilateral. The presence of more than 4 widely spaced, small (<0.5-disc-diameter) lesions per eye and bilateral involvement suggest FAP. Note that congenital grouped pigmentation (“bear tracks”) is not associated with FAP. Caused by mutations in the adenomatous polyposis gene (APC), FAP has an autosomal dominant inheritance pattern with incomplete expression. The pigmented retinal lesions are an important marker for identifying family members at risk of colonic polyps, which have a high malignant potential.
Ichthyosis, comprising abnormal scaling, dryness, and tightness of the skin, may be found in conjunction with the pigmentary retinopathy of Refsum disease and the crystalline maculopathy of Sjögren-Larsson syndrome. Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare, X-linked disorder that presents only in females; the mutation is lethal in males. It is characterized by streaky skin lesions and abnormalities of the teeth and central nervous system (CNS). Ocular involvement occurs in approximately one-third of affected females and includes pigmentary abnormalities as well as peripheral retinal nonperfusion and neovascularization that may cause tractional and cicatricial retinal detachment (also see BCSC Section 6, Pediatric Ophthalmology and Strabismus). Pseudoxanthoma elasticum is associated with a “plucked-chicken” skin appearance, peripapillary angioid streaks, and a peau d’orange fundus appearance (see Chapter 4).
Holmström G, Thorén K. Ocular manifestations of incontinentia pigmenti. Acta Ophthalmol Scand. 2000;78(3):348–353.
Traboulsi EI. Ocular manifestations of familial adenomatous polyposis (Gardner syndrome). Ophthalmol Clin North Am. 2005;18(1):163–166.
Amelogenesis imperfecta is a genetic disease that causes abnormalities in dentition development resulting from defective enamel production. When associated with a cone–rod dystrophy this condition is referred to as Jalili syndrome and has a wide range of clinical retinal manifestations, including macular coloboma and pigmentary retinopathy.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.