Abstract
Purpose :
To report the ophthalmologic and genetic analysis of an autosomal dominant kindred in which the 13-year old proband presented with reduced vision.
Methods :
The proband and her asymptomatic parents were assessed after referral by the proband’s paediatric ophthalmologist for investigation of progressive vision loss. Investigations performed included: ETDRS visual acuity, Lanthony D-15 colour vision testing, Goldmann perimetry, full-field and multifocal electroretinograms (ERG; mfERG), pattern visual evoked response and pattern electroretinogram, colour and autofluorescent fundus photography and optical coherence tomography. Gene sequencing was carried out in diagnostically accredited laboratories.
Results :
Ophthalmological testing established evidence of macular dysfunction in the proband and her father, more advanced in the proband. Both had tritan colour vision defects and marked attenuation of mfERG response amplitudes in the central segments and preservation of amplitudes in peripheral segments. The proband’s ERG was normal. At the time of examination neither individual reported any significant neurological symptoms.
Coincident with the diagnosis of an autosomal dominant maculopathy, genetic screening of the proband’s paternal grandfather, who had succumbed to Multiple System Atrophy, revealed a pathogenic ~37 CAG repeat (upper limit of normal = 35) in one ATXN7 allele. Sequencing of the proband revealed a heterozygous ~55 repeat, while her father was heterozygous for a ~39 repeat, refining the clinical diagnosis as Spinocerebellar Ataxia Type 7 (SCA7).
Conclusions :
SCA7 is a rare autosomal dominant neurodegeneration due to > 35 CAG expansion repeats in ATXN7. Anticipation, an increase in the repeat number from parent, particularly paternal, to child, occurs. SCA7 is highly variable clinically, the age of onset and severity inversely related to the repeat number. Typically, patients present with signs of Cerebellar Ataxia and visual loss due to a cone-rod dystrophy, however, vision loss may precede the ataxic features. Notably, the proband’s cone and rod ERG responses were normal.
This report indicates that a tritan colour vision defect and mfERG disturbance may be early signs of macular dysfunction in SCA7. This constellation of clinical findings, together with greater compromise in offspring compared to parent, should alert the clinician to the possibility of ATXN7 as a genetic cause, with its resultant neurological implications.
This is a 2020 ARVO Annual Meeting abstract.