There are limited reports of Best’s disease in children younger than 3 years. This is a case series of two family members aged 10 and 31 months with Best’s disease. To the authors’ knowledge, the 10-month-old male infant is the youngest patient with Best’s disease documented by fundus photography.
[J Pediatr Ophthalmol Strabismus 2014;51:e8–e12.]
From Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
Dr. Berrocal is a consultant for Thrombogenics and Genentech. The remaining authors have no financial or proprietary interest in the materials presented herein.
Correspondence: Audina M. Berrocal, MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136. E-mail:
Received: June 16, 2013
Accepted: January 06, 2014
Posted Online: March 04, 2014
Best’s vitelliform macular dystrophy (Best’s disease, OMIM 153700) is a slowly progressive retinal disorder that can lead to decreased central visual acuity. Best’s disease has autosomal dominant inheritance with variable expression and incomplete penetrance of the BEST1 (VMD2) gene1 on chromosome 11q132; however, there are also reports of autosomal recessive inheritance.3 Best’s disease is diagnosed with a funduscopic examination showing unilateral or bilateral macular lesions characterized by yellow, yolk-like features that are 0.5 to 3.0 disc diameters and surrounded by a darker border.4 The yellow color is due to the accumulation of lipofus-cin.5 Electrooculogram testing with a light peak/dark trough (Arden ratio) less than 1.5 can confirm a clinical diagnosis or diagnose patients who do not have classic lesions. Early childhood and later teenage years are the most common ages of disease onset. Some authors report that macular findings are seen during the first year of life,3 whereas others report retinal findings at age 5 to 10 years.6
There are a limited number of publications of Best’s disease in patients 3 years old or younger.3,7–11 A 20-month-old boy is the youngest patient in the literature to have Best’s disease documented with photographic evidence.11 We describe two siblings with Best’s disease: a 31-month-old girl and a 10-month-old male infant. The 10-month-old male infant appears to be the youngest patient with photographic evidence of Best’s disease.
A 10-month-old asymptomatic male infant was evaluated by the pediatric retina service when his older sister (case 2) was referred for evaluation of a macular lesion. The male patient had no previous ocular examinations and no medical problems. The parents reported that he was able to track and reported no abnormalities in the child’s vision.
The child was able to fix and follow in both eyes. Pupils were round and reactive in both eyes, with no relative afferent pupillary defects. Adnexa and anterior segment examinations were unremarkable.
Fundus photography and color negative images of the fundi (Figure 1) demonstrated bilateral retinal pigment epithelial mottling with a circular macular lesion measuring 1 disc diameter. The circular lesions were more pronounced on the color negative images photographs (Figures 1C–1D). Retinal pigment epithelial mottling is consistent with the previtelliform stage of Best’s disease. Optical coherence tomography (OCT) testing was not conducted on this patient.
(A) Right and (B) left fundus photographs of the 10-month-old male infant (case 1) showing bilateral retinal pigment epithelial mottling and a circular macular lesion. Color negative fundus images of the (C) right and (D) left eyes.
The patient’s family history was significant for Best’s disease in his father. Fundus photographs of the father (Figures 2A–2B) revealed well-circumscribed macular lesions of approximately three disc diameters with a yellowish collection of fluid inferiorly consistent with the pseudohypopyon phase of Best’s disease. OCT images demonstrated splitting and elevation of the outer retina–retinal pigment epithelium complex (Figures 2C–2D).
(A) Right and (B) left fundus photographs of the father of cases 1 and 2 showing the pseudohypopyon phase of Best’s disease. Optical coherence tomography images of the (C) right and (D) left eyes.
A 31-month-old girl was referred to the pediatric retina service by a pediatric ophthalmologist for evaluation of a macular lesion that was suspected Best’s disease. The patient had a history of amblyopia in the right eye and hyperopia, but had no other medical problems. The family history was significant for Best’s disease in her father (Figure 2).
The child’s best-corrected visual acuity was 20/40 in the right eye and 20/30 in the left eye wearing +5.25 sphere, +5.00 sphere glasses. Pupils were round and reactive in both eyes, with no relative afferent pupillary defects. External examination was significant for a right esotropia. Anterior segment examination was unremarkable.
Funduscopic photographs (Figures 3A–3B) showed a well-circumscribed, yellow-orange circular macular lesion in both eyes with hyperpigmented borders consistent with the vitelliform stage of Best’s disease. OCT images (Figures 3C–3D) demonstrated deposition of material in the subretinal space with splitting of the outer retina–retina pigment epithelium complex at the level of the fovea.
(A) Right and (B) left fundus photographs of the 31-month-old girl (case 2) showing bilateral vitelliform lesions. Optical coherence tomography images of the (C) right and (D) left eyes.
Best’s disease is a rare disorder that can lead to a significant decline in visual acuity, usually after the fifth decade of life. Early diagnosis is important to educate families and to initiate long-term monitoring and treatment.
Patients generally progress along five different stages: previtelliform, vitelliform, pseudohypopyon, vitelliruptive, and fibrotic, but lesions can encompass two or more stages simultaneously.7 Most patients retain sufficient visual acuity for reading and driving despite the development of large lesions. Peripheral vision and dark adaptation remain intact. In one study, 88% of patients had visual acuity of 20/40 or better in their better eye and 77% had 20/40 or better in both eyes when observed for at least 5 years.12 Other research, with a mean follow-up of 15.3 years, reported that almost everyone in a cohort of 40 patients with Best’s disease had a slow decline in visual acuity without becoming legally blind.10
Visual decline can occur rapidly with the development of subretinal hemorrhages and choroidal neovascularization, which is usually asymmetric. Early recognition and prompt treatment of choroid neovascularization may improve visual outcomes, especially in children young enough to be at risk for ambylopia. Avoidance of contact sports may reduce the risk of subretinal hemorrhages and rapid visual decline.
Early diagnosis can help families obtain genetic counseling about the risk of Best’s disease in future pregnancies. Best’s disease is primarily characterized by autosomal dominant inheritance, so siblings of affected patients have up to a 50% chance of developing the disease and patients have up to a 50% chance of passing the disease on to their children. Screening pediatric patients with a family history of Best’s disease may help identify patients, educate family members, and possibly reduce the risk of developing significant visual decline.
- Petrukhin K, Koisti MJ, Bakall B, et al. Identification of the gene responsible for Best macular dystrophy. Nat Genet. 1998;19:241–247. doi:10.1038/915 [CrossRef]
- Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC. Genetic linkage of vitelliform macular degeneration (Best’s disease) to chromosome 11q13. Nat Genet. 1992;1:246–250. doi:10.1038/ng0792-246 [CrossRef]
- Kinnick TR, Mullins RF, Dev S, et al. Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients. Retina. 2011;31:581–595. doi:10.1097/IAE.0b013e318203ee60 [CrossRef]
- August Deutman CH, van Lith-Verhoeven Janneke. Macular dystrophies. In: Schachat A, ed. Retina, 4th ed. St. Louis, MO: Mosby; 2006:1177–1181.
- O’Gorman S, Flaherty WA, Fishman GA, Berson EL. Histopathologic findings in Best’s vitelliform macular dystrophy. Arch Ophthalmol. 1988;106:1261–1268. doi:10.1001/archopht.1988.01060140421045 [CrossRef]
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- Querques G, Zerbib J, Santacroce R, et al. Functional and clinical data of Best vitelliform macular dystrophy patients with mutations in the BEST1 gene. Mol Vis. 2009;15:2960–2972.
- Cohn AC, Turnbull C, Ruddle JB, et al. Best’s macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations. Eye (Lond). 2011;25:208–217. doi:10.1038/eye.2010.180 [CrossRef]
- Booij JC, Boon CJ, van Schooneveld MJ, et al. Course of visual decline in relation to the Best1 genotype in vitelliform macular dystrophy. Ophthalmology. 2010;117:1415–1422. doi:10.1016/j.ophtha.2009.11.044 [CrossRef]
- Kovach JL, Schwartz SG, Hickey M, McKeown CA. Best’s disease in a 20-month-old child. J Pediatr Ophthalmol Strabismus. 2009;48:E1–E3.
- Mohler CW, Fine SL. Long-term evaluation of patients with Best’s vitelliform dystrophy. Ophthalmology. 1981;88:688–692. doi:10.1016/S0161-6420(81)34965-3 [CrossRef]