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Phenotypic variation in a family with pseudodominant stargardt disease
Journal article   Open access   Peer reviewed

Phenotypic variation in a family with pseudodominant stargardt disease

Rachel M Huckfeldt, Jade S East, Edwin M Stone and Elliott H Sohn
JAMA Ophthalmology, Vol.134(5), pp.580-583
2016
DOI: 10.1001/jamaophthalmol.2015.5471
PMID: 27030965
url
https://doi.org/10.1001/jamaophthalmol.2015.5471View
Published (Version of record) Open Access

Abstract

Importance: Stargardt disease is a phenotypically diverse macular dystrophy caused by the autosomal recessive inheritance of mutations in ABCA4. Pseudodominant transmission occurs more often than might be expected because of the relatively high carrier frequency of pathogenic ABCA4 variants. Genetic characterization of affected individuals permits a more precise understanding of these genotype-phenotype associations.Observations: In this case series, we explore the clinical courses and genotypes of a woman and her 2 daughters with pseudodominant transmission of Stargardt disease. The mother had choroidal neovascularization that was treated with bevacizumab. Both daughters exhibited worse vision than their mother, despite lacking choroidal neovascularization, because of the extent of photoreceptor and retinal pigment epithelium atrophy in the macula. Genetic testing confirmed pseudodominant inheritance and the presence of 3 ABCA4 alleles within the family.Conclusions and Relevance: These cases emphasize the clinical relevance of recognizing pseudodominant transmission and the resultant phenotypic variability. Differing degrees of visual impairment in these patients emphasize the need to continue refining our understanding of how individual ABCA4 mutations contribute to phenotype.

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