IllnessVitreoretinopathy, exsudative familial; differential diagnosis

NGS +

[Sanger]

Familial exudative vitreoretinopathy can lead to progressive vision loss as the retina is attacked. The disease reduces the blood supply, especially at the retinal edges. The symptoms of familial exudative vitreoretinopathy vary widely, even within the same family. In many affected people, the retinal abnormalities do not cause any visual problems. In others, the reduced blood supply causes the retina to fold, tear or even detach. Other eye abnormalities are also possible, such as strabismus and leukocoria. Some patients also show reduced bone mineral density. Mutations in the FZD4, LRP5, NDP, TSPAN12 and ZNF408 genes can cause the disease with very similar symptoms, although reduced bone mineral density is often observed especially due to mutations of the LRP5 gene. Familial exsudative vitreoretinopathy is inherited differently depending on the gene affected. Most often, the disease is caused by mutations in the FZD4 or LRP5 genes with autosomal dominant inheritance. In the case of LRP5 mutations, the disease can also be inherited in an autosomal recessive manner. Mutations in the NDP gene cause X-linked recessive vitreoretinopathy. The differential diagnosis includes many other genes with (partly) very similar symptoms, such as the Stickler syndrome genes (COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, COL9A3) etc. In a few cases of familial exudative vitreoretinopathy, however, a molecular genetic cause cannot be determined at present. Therefore, a negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1331/

https://www.ncbi.nlm.nih.gov/books/NBK3821/

https://www.ncbi.nlm.nih.gov/books/NBK1302/

• Sympt.: incomplete development of retinal vasculature: from blind to mildly affected
• Allelic: Bestrophinopathy, AR (BEST1)
• Allelic: Bone mineral density variability 1 (LRP5)
• Allelic: Hyperostosis, endosteal (LRP5)
• Allelic: Leber congenital amaurosis 16 (KCNJ13)
• Allelic: Macular dystrophy, patterned, 2 (CTNNA1)
• Allelic: Macular dystrophy, vitelliform, 2 (BEST1)
• Allelic: Microcornea, rod-cone dystrophy, cataract + posterior staphyloma (BEST1)
• Allelic: Norrie disease (NDP)
• Allelic: Osteopetrosis, AD 1 (LRP5)
• Allelic: Osteoporosis (LRP5)
• Allelic: Osteoporosis-pseudoglioma syndrome (LRP5)
• Allelic: Osteosclerosis (LRP5)
• Allelic: Polycystic liver disease 4 with/-out kidney cysts (LRP5)
• Allelic: Retinitis pigmentosa 37 (NR2E3)
• Allelic: Retinitis pigmentosa 50 (BEST1)
• Allelic: Retinitis pigmentosa 72 (ZNF408)
• Allelic: Retinitis pigmentosa, concentric (BEST1)
• Allelic: Retinopathy of prematurity (FZD4)
• Allelic: Retinoschisis (RS1)
• Allelic: van Buchem disease, type 2 (LRP5)
• Enhanced S-cone syndrome (NR2E3)
• Exudative vitreoretinopathy 1 [Criswick-Schepens syndrome] (FZD4)
• Exudative vitreoretinopathy 2, XL (NDP)
• Exudative vitreoretinopathy 4 (LRP5)
• Exudative vitreoretinopathy 5 (TSPAN12)
• Exudative vitreoretinopathy 6 (ZNF408)
• Exudative vitreoretinopathy 7 (CTNNB1)
• Exudative vitreoretinopathy [MONDO:0019516] (CTNNA1)
• Knobloch syndrome, type 1 (COL18A1)
• Marshall syndrome (COL11A1)
• Microcephaly + chorioretinopathy, AR, 3 (TUBGCP4)
• Microcephaly with/-out chorioretinopathy, lymphedema/mental retardation (KIFF11)
• Myopia, high, with cataract and vitreoretinal degeneration (P3H2)
• Persistent hyperplastic primary vitreous, AR (ATOH7)
• Retinal dystrophy with/-out extraocular anomalies (RCBTB1)
• Retinochisis (RS1)
• Snowflake vitreoretinal degeneration (KCNJ13)
• Stickler sydrome, type I, nonsyndromic ocular (COL2A1)
• Stickler syndrome, type I (COL2A1)
• Stickler syndrome, type II (COL11A1)
• Stickler syndrome, type III (COL11A2)
• Stickler syndrome, type IV (COL9A1)
• Vitreoretinochoroidopathy (BEST1)
• Vitreoretinopathy with phalangeal epiphyseal dysplasia (COL2A1)
• Vitreoretinopathy, neovascular inflammatory (CAPN5)
• Wagner syndrome 1 (VCAN)