Clinical Characteristics
Ocular Features
There exist a considerable number of disorders often classified under the heading of ‘flecked retina’ syndrome. Prior to the modern genomic period, distinctions among them were based on the clinical picture, functional abnormalities, and electrophysiological studies. The nosology is becoming clearer as more individuals are genotyped and we can expect further discrimination of these disorders in the near future.
White or yellow discrete dots are found throughout the fundus. These are most dense in the midperiphery RPE and the macula is generally not involved. This is most common in patients with fundus albipunctatus who have a nonprogressive disease. Stationary night blindness is the predominant symptom. However, patients with mutations in RDH5 may have more serious cone involvement and progressive macular disease. Visual acuity varies from near normal to severe loss. Photopic ERGs may be normal but only low scotopic responses can be recorded in such patients. Cone dysfunction is more severe in older patients.
Systemic Features
No systemic disease is associated with these syndromes.
Genetics
Inheritance
These disorders are sometimes grouped into the category of 'flecked retina disease'.
Autosomal dominant inheritance is typical for fundus albipunctatus (136880) resulting from mutations in the RDS (PRPH2) gene (6p21.1-cen).
Autosomal recessive fundus albipunctatus (136880) is caused by mutations in RDH5 (12q13-q14) and sometimes in RLBP1 (15q26.1).
Retinitis punctata albescens (136880) and fundus albipunctatus (136880) may both be caused by mutations in RLBP1 (15q26.1). In a consanguineous family in which younger individuals (aged 3-20 years) had signs of fundus albipunctatis, older individuals in the fourth and fifth decades of life had features of retinitis punctata albescens (136880). Homozygous mutations in RLBP1 were found in all individuals. Homozygous mutations in the same gene are also responsible for Bothnia type retinal dystrophy (607475) and for the Newfoundland type of retinal dystrophy (607476).
Familial Benign Fleck Retina (228980) is characterized by a normal ERG and normal vision. The macula is spared from the white/yellow flecks located behind retinal vessels. Autofluorescence is present and the fluorescein angiogram shows irregular hypofluorescence. Nothing is known about the mutation but the clinical condition is inherited in an autosomal recessive pattern.
Some group Stargardt disease (248200), fleck retina of Kandori (228990), juvenile retinoschisis (312700), and familial benign fleck retina (228980) as well into the category of 'flecked retina disease'.
Other disorders in which retinal flecks may be seen are: spastic paraplegia 15 (270700), hyperoxaluria (259900), Alport syndrome (301050), Bietti-crystalline-corneoretinal-dystrophy (210370 ), Sjogren-Larsson syndrome (270200), pantothenate kinase-associated neurodegeneration (234200), Leber congenital amaurosis (204000), and Bardet-Biedl syndrome (209900),
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.