Variable expressivity of -associated autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a three-generation pedigree.

TitleVariable expressivity of -associated autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a three-generation pedigree.
Publication TypeJournal Article
Year of Publication2021
Authorsda Palma, MMatioli, Vargas, ME, Burr, A, Chen, R, Pennesi, ME, Weleber, RG, Yang, P
JournalBMJ Open Ophthalmol
Date Published2021

OBJECTIVE: Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is associated with pathogenic variants in , which typically causes visual impairment in the late stage of disease. We present a pedigree with variable expressivity and the youngest case in the literature with visual impairment in early childhood.

METHODS AND ANALYSIS: This is a retrospective, observational, case series describing multigenerational members of one family affected with ADVIRC. Patients underwent examination, ultra-widefield fundus photography and angiography, optical coherence tomography, full-field electroretinography (ffERG) and full-field perimetry.

RESULTS: Three affected members of the pedigree, one from each successive generation, were found to harbour a mutation, c.715G>A:p.Val239Met, in . The proband characterised in this report is, to our knowledge, the youngest documented case of ADVIRC in early childhood. Yet, this patient has the most severe retinal dysfunction compared with the father and paternal grandmother, whom exhibit classic characteristics of ADVIRC. Longitudinal data from the paternal grandmother showed that there was a rapid decline in ffERG responses (photopic decline worse than scotopic) from the fourth to fifth decade of life, which correlated with severe concentric constriction of visual fields.

CONCLUSION: This multigenerational case series provides new insights into the ADVIRC disease spectrum and rate of progression. While ADVIRC typically causes a slowly progressive disease, we show that variable phenotypic expressivity is possible among affected members of the same family with the same mutation in . Thus, ADVIRC must also be considered in the differential diagnosis of paediatric patients with severe retinal dystrophy in early childhood.

Alternate JournalBMJ Open Ophthalmol
PubMed ID34746433
PubMed Central IDPMC8532547
Grant ListK08 EY026650 / EY / NEI NIH HHS / United States
P30 EY010572 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States