Macular dystrophies associated with Stargardt-like phenotypes

Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings.

Methods:

This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes.

Results:

Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic.

Conclusion:

Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

Keywords:
Stargardt disease; Genetic association studies; Phenotype; Inheritance patterns; High-throughput nucleotide sequencing; Macular degeneration; Retinal dystrophies; Genetic diseases

Patient	Sex	Age of onset (years)	Visual acuity (RE; LE)	Symptoms at the time of diagnosis	Fundus examination		Allele 1		Allele 2
Patient	Sex	Age of onset (years)	Visual acuity (RE; LE)	Symptoms at the time of diagnosis	Fundus examination	Gene	Nucleotide change	Protein change	Nucleotide change	Protein change	Inheritance pattern
1	F	40	20/40; 20/40	Delayed dark adaptation and nyctalopia	Macular flecks and pigmentary changes	RIMS1	c.2093G>A	p.Arg698Gln	-	-	AD
2	M	48	20/200; 20/30	Loss in central vision in the RE	Macular atrophy in the RE and bull’s eye in the LE	CRX	c.121C>T	p.Arg41Trp	-	-	AD
3	M	12	20/60; 20/60	Delayed dark adaptation and loss in central vision	Yellow deposits in the macular area and pigmentary changes	CRB1	c.2843G>A	p.Cys948Tyr	c.408_506del	p.Ile167_Gly169del	AR
4	F	40	20/60; 20/60	Photophobia, loss in central vision	Macular and paramacular atrophy	RDH12	c.295C>A	p.Leu99Ile	c.700C>T	p.Arg234Cys	AR

Patient		Fundus examination	Gene	Allele 1		Allele 2
Patient		Fundus examination	Gene	Nucleotide change	Protein change	Nucleotide change	Protein change
1	Daughter	Macular atrophy and pigmentary changes	RIMS1	c.2093G>A	p.Arg698Gln	-	-
3	Mother	Narrow vessels and macula edema	CRB1	c.613_619del	p.Ile205Asp fs^*13	c.408_506del	p.Ile167_Gly169del

Patient	Findings that suggest STGD1	Findings that differentiate from STGD1
1	Flecks around the macula and posterior pole	AD inherited pattern
2	Foveal hypoautofluorescence surrounded by a homogeneous retina	Asymmetric VA
3	Macular atrophy and pigmentary changes	Cystoid macular edema in te retina of the mother
4	Macular atrophy and preserved vessels	Different hypoautofluorescence macular aspect in FAF

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[1] Correspondence author: Juliana Maria Ferraz Sallum. E-mail: juliana@pobox.com