Hereditary Vitreoretinopathies: Molecular Diagnosis, Clinical Presentation and Management

Abstract

Hereditary vitreoretinopathies (HVRs), also known as hereditary vitreoretinal degenerations comprise a heterogeneous group of inherited disorders of the retina and vitreous, collectively and variably characterised by vitreal abnormalities, such as fibrillary condensations, liquefaction or membranes, as well as peripheral retinal abnormalities, vascular changes in some, an increased risk of retinal detachment and early-onset cataract formation. The pathology often involves the vitreoretinal interface in some, while the major underlying abnormality is vascular in others. Recent advances in molecular diagnosis and identification of the responsible genes and have improved our understanding of the pathogenesis, risks and management of the HVRs. Clinically, HVRs can be classified according to the presence or absence of skeletal or other systemic abnormalities, retinal dysfunction or retinal vascular abnormalities [2]. There are some discrepancies in the literature regarding which diseases are included under the overarching term 'hereditary vitreoretinopathies'. Conditions such as Stickler syndrome, Wagner syndrome and familial exudative vitreoretinopathy are generally included, while others such as autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) and autosomal dominant vitreoretinochoroidapathy (ADVIRC) may not. In this review, we will discuss some historical aspects, the molecular pathogenesis, clinical features and management of diseases and syndromes commonly considered as HVRs.

Keywords: Stickler syndrome; familial exudative vitreoretinopathy; hereditary vitreoretinopathy; retinal detachment; vascular disorders.

FIGURE 1

Right (A) and left (B) wide‐angle fundus photographs of a patient with Stickler syndrome. Note: Areas of white without pressure and abnormal vitreoretinal interface reflexes. There are scattered laser scars in the peripheral fundus.

FIGURE 2

Posterior pole of the right eye of a patient with Knobloch syndrome. Note: Myopic appearance and the round sharply demarcated atrophic lesion on the temporal edge of the fovea.

FIGURE 3

(A and B) Right and left posterior pole images in a patient with FZD4 mutation. (C and D) Same patient's temporal periphery showing dragged macula, subretinal exudate and peripheral ischemia treated with laser. (E and F) Left eye fluorescein angiogram in a patient with TSPAN12 mutation. (G and H) Posterior pole in a patient with a LRP5 variant of undetermined significance, showing a pattern of heavy exudates and telangiectatic vessels more typical of a telomere disorder. (I and J) Typical dragged macula with peripheral ischemia in a patient with LRP5 mutation.

FIGURE 4

Fundus photo (A), angiogram (B–D) and OCT of retinal fold formation in a patient with FEVR and a pathogenic FZD4 sequence variant.

FIGURE 5

Fluorescein angiogram of the right fundus of a patient with pathogenic CTC1 variant. Note: Peripheral areas of non‐perfusion and the presence of telangiectatic vessels.