Prominent Optic Disc Featured in Inherited Retinopathy

Abstract

Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD).

Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology.

Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1. In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1. In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4. In the fourth family, POD with “mulberry-like” deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A, and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1. In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS, thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease.

Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out.

Zusammenfassung

Hintergrund Wir untersuchten mögliche Zusammenhänge einer Papillenprominenz (POD) unter verschiedenen erblich bedingten Netzhauterkrankungen (IRDs).

Material und Methoden Querschnittsstudie an 10 Kindern und 11 Erwachsenen aus 7 nicht miteinander verwandten betroffenen Familien. Der klinische Phänotyp wurde mithilfe einer gründlichen klinischen Untersuchung einschließlich Fundusautofluoreszenz-Aufnahmen, Farbfotodokumentation und OCT-Bildgebung bestimmt und mit der genetischen Abklärung aller teilnehmenden Familienmitglieder ergänzt.

Ergebnisse In 4 Mitgliedern innerhalb einer 3-Generationen-Familie zeigten sich oberflächliche, hyperfluoreszente Ablagerungen an der Papille sowie eine POD in Zusammenhang mit einer heterozygoten Mutation in p.(L224M) im BEST1-Gen. In der zweiten Familie zeigte ein Patient oberflächliche Ablagerungen auf einer hyperämen Papille in Zusammengang mit einer p.(R141H);(A195V) Mutation im BEST1-Gen. In der dritten Familie fanden wir eine POD im Rahmen einer früh einsetzenden Zapfen-Stäbchen-Dystrophie bei Vater und Kind in Zusammengang mit einer autosomal rezessiven homozygoten Neumutation in p.(W31*) im ABCA4-Gen. Innerhalb der vierten Familie fanden wir bei einem 7-jährigen Mädchen mit einer früh einsetzenden Stäbchen-Zapfen-Dystrophie, begleitet von Hörverlust und einer Mutation im USH1A-Gen, beerenartige Ablagerungen an der Papille sowie verdünnte Netzhautgefäße. Innerhalb der fünften Familie zeigten sich eine POD und Tortuositas vasorum bei 4 verwandten weiblichen Trägerinnen und einem betroffenen Jungen mit einer homozygoten p.(R200H)-Mutation im RS1-Gen im Zusammenhang mit einer X-chromosomalen Retinoschisis. In der sechsten Familie fanden wir bei einer Mutter und ihrem Sohn, beide betroffen von einer autosomal dominanten RP mit einer heterozygoten p.(Y836C)-Mutation im TOPORS-Gen, sowohl eine POD als auch verdünnte peripapilläre Gefäße. Bei der siebten Familie zeigten 3 Familienmitglieder eine POD. Die genetische Abklärung ergab bei allen eine p.(L541P;A1038 V);(G1961E) Mutation im ABCA4-Gen und bestätigte unsere Diagnose eines Morbus Stargardt.

Schlussfolgerung Innerhalb der sehr heterogenen Gruppe der IRDs finden sich unterschiedliche Papillenbefunde. Bei einer Papillenprominenz sollte ein genetisch bedingter Photorezetorverlust ausgeschlossen werden.

Key words

prominent optic disc - inherited retinopathy - mutation

Schlüsselwörter

Papillenprominenz - erblich bedingte Netzhauterkrankung - Mutation

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