Three male siblings of a nonconsanguineous Chinese family exhibited characteristic retinal crystalline flecks of Bietti crystalline retinopathy (BCR). The main proband suffered from blurred and distorted vision and also had bilateral submacular scars. To our knowledge, the presence of BCR in this family demonstrated the strongest male preponderance among the reported cases in the English literature. The mode of inheritance could be X-linked recessive, but no conclusion could be made because the pedigree studied was too small.
A 38-year-old Chinese man (the main proband) was referred to our hospital in 1991 for a 1-year history of night blindness, metamorphopsia, and slowly progressive visual loss. The left eye was more severely affected. He was the second child in his family and his parents were not related (Figure 1). He was not obese and findings from the medical and drug history were normal. On examination, visual acuity was 20/70 OD and 20/100 OS. The cornea was clear with no crystals. Findings from fundus examination showed multiple fine yellow-white refractile crystalline flecks scattered throughout both of the posterior poles and the periphery of the fundi. They situated in all layers of the neurosensory retina, and some crystals lay on top of the retinal vessels. Several areas of blotchy pigment clumping were noticed in the mid-periphery. The optic discs and retinal vessels were normal. A left subretinal scar lying 1–disc diameter temporal and inferior to the fovea and a similar but somewhat fainter right scar lying about 2–disc diameters temporal to the fovea were evident (Figure 2).
Pedigree chart of the family. Numbers 1, 2, and 3 indicate patients 1, 2, and 3.
Patient 1 (the main proband). Color fundus photographs of the right (left) and left (right) eyes showing glistening crystals scattered throughout the posterior fundus and extended into the periphery, patches of pigment clumping, and retinal pigment epithelial hypopigmentation and atrophy. Subretinal scars (arrows) were found in the macular area of both eyes.
Visual field testing using the Humphrey Field Analyzer showed bilateral paracentral scotomas. Color vision tested with the Ishihara color chart was normal. Findings from fluorescein angiography of the late venous phase showed areas of hyperfluorescence interspersed with hypofluorescent regions and the associated prominent choroidal vessels. These features suggested atrophic changes of both the retinal pigment epithelium and the choriocapillaries. The crystals did not show up on the angiogram. No neovascular membrane, gross leakage and pooling of fluorescein dye from vessels, or gross macular edema was seen. Full-field electroretinography recorded diminishment in amplitude of all waveforms, especially the cone response. Findings from electro-oculographic examination showed subnormalities with decreased dark to light ratio.
Values from routine blood biochemistry tests, including fasting triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol, and apolipoprotein B were normal. Oxalic acid and amino acid analysis in 24-hour urine samples also gave normal results. Leukocyte cystine level and α-galactosidase A activity were within reference intervals. The expression of the ornithine aminotransferase gene was also normal. The patient had been followed up in our hospital for 7 years. His vision remained stable, but the retinopathy showed advancement in atrophic changes over the retinal pigment epithelial layer, and the crystals became less prominent.
Cases 2 and 3, aged 34 and 36 years, respectively, were the younger brothers of the main proband. Both of them were asymptomatic, had an unremarkable medical or drug history, and their visual acuity was 20/20 OU. Findings from ocular examination were normal except for the presence of bilateral multiple crystalline flecks in the retinas. These retinal flecks were confined to the posterior pole. There were fewer deposits when compared with that of the proband (Figure 3), and the youngest brother had the fewest deposits (Figure 4). Both corneas were clear with no deposits. Findings from systemic and ocular testing, including blood biochemistries, molecular analyses, visual field, electroretinogram, and electro-oculogram, were all normal.
Patient 2. Color fundus photographs of the right (left) and left (right) eyes showing many tiny reflective crystals mainly over the posterior poles. The retinal pigmented epithelial atrophy was not marked.
Patient 3. Color fundus photographs of the right (left) and left (right) eyes showing only a few crystals around the macula.
The normal drug and medical history, results of ophthalmologic examination, biochemistry tests, and molecular analysis support the diagnosis of BCR without corneal involvement. We have conducted comprehensive ocular examinations for all other family members as shown in the pedigree tree (Figure 1). Findings from these examinations were normal.
The presence of refractile bodies and crystalline deposits over both retinas may be owing to primary eye diseases or secondary effects of inherited or acquired metabolic diseases. Differential diagnosis is important for appropriate treatment. Diffuse crystalline retinal deposits may occur in systemic oxalosis, cystinosis, hyperornithinemia, talc retinopathy, Sjögren-Larsson syndrome, and excessive intake of tamoxifen or canthaxantine. Clinical and biochemical features of our cases are not consistent with any of these disorders.
There are about 90 reported cases of BCR with considerable variation in symptoms and retinopathy.1- 5 Some have characteristic fundal pictures as originally described by Bietti.6,7 Some have simultaneous corneal and retinal involvement. Pure retinal involvement appears to be more common in Asian than white people.1,2 This intrafamilial phenotypic variability typifies the heterogeneity of BCR and has been well shown in our cases.
Our main proband had neither high myopia nor a history of choroiditis. He had bilateral crystalline retinopathy with subretinal fibrosis in the posterior poles. Maculopathy in Bietti dystrophy is uncommon. Macular holes have been reported in 2 cases in which 1 was highly myopic.1- 3 The submacular scar in the first patient could be the result of a subretinal neovascular membrane, which, to our knowledge, could represent the first case reported in the English literature and highlights the clinical diversity of BCR. However, whether it is related to the dystrophy and the mechanism of its formation is not clear.
The proportion of male and female patients with BCR is similar, but there was segregation of male and female patients in some families. In one reported family, 8 of 9 of those affected were women.4 In general, however, BCR usually occurs sporadically and is more common among siblings or in families with consanguineous marriage; an autosomal recessive mode of inheritance is generally regarded.1 Richards et al4 described an autosomal dominant inheritance of high penetrance in a family with BCR. They even suggested that it should be regarded as a new disease entity. In our family, all of the male siblings (3) in the second generation were affected despite the different magnitudes, while their unrelated parents and the only sister were unaffected. The X-linked recessive mode of inheritance is possible, but no conclusion could be made as the pedigree of the current family is too small.
Corresponding author: Dennis S. C. Lam, FRCS, FRCOphth, Chairman, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (e-mail: firstname.lastname@example.org).
This study was supported in part by the W. K. Lee Eye Foundation, Shatin, Hong Kong.
Chan W, Pang C, Leung ATS, Fan DSP, Cheng ACK, Lam DSC. Bietti Crystalline Retinopathy Affecting All 3 Male Siblings in a Family. Arch Ophthalmol. 2000;118(1):129-131. doi: