Alternative titles; symbols
SNOMEDCT: 312926005; ORPHA: 75376; DO: 0060746;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q31.3 | Basal laminar drusen | 126700 | Autosomal dominant | 3 | CFH | 134370 |
A number sign (#) is used with this entry because of evidence that a variant of the CFH gene (134370) influences the development of basal laminar drusen.
Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. They appear as slightly raised, yellow subretinal nodules randomly scattered in the macula. 'Drusen' is the plural for 'Druse,' German for 'nodule' or 'crystal' (summary by Bok, 2002, Boon et al., 2008).
'Basal laminar drusen' refers to an early adult-onset drusen phenotype that shows a pattern of uniform small (25- to 75-micrometer), slightly raised yellow subretinal nodules randomly scattered in the macula (Boon et al., 2008). The term 'basal laminar drusen' is widely used but may be a misnomer because these deposits do not appear to correspond with nodular or diffuse thickening of the Bruch membrane. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. On fluorescein angiography, a typical 'stars in the sky' appearance may be observed. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.
Deutman and Jansen (1970) described a family in which 8 persons in 5 sibships had confirmed multiple drusen of Bruch membrane. There was no instance of male-to-male transmission but an affected male had 2 daughters who were negative by examination. They observed concordant monozygotic twins and affected boys 12 and 14 years old. They concluded that the family with 'crystalline retinal degeneration' reported by Evans (1950) had this condition. The authors also concluded that Doyne honeycomb choroiditis (126600) is the same condition. Round or oval lesions in almost grape-like clusters are concentrated in the posterior polar region. Pigmentary disturbances with secondary calcifications occur. The macula is almost always involved and may appear edematous or hemorrhagic. Loss of vision occurs during the progressive stages. This is considered a form of fleck retina disease (see 228980).
Bok (2002) stated that there was widespread agreement among ophthalmologists that numerous large drusen, when present in both eyes, represent a significant risk factor for the evolution of early age-related macular dystrophy (ARMD1; 603075) into more advanced ARMD, with loss of central vision.
To understand the molecular basis of drusen formation, Crabb et al. (2002) developed a method for isolating microgram quantities of drusen and Bruch membrane for proteome analysis. They found oxidative protein modifications in drusen, supporting the hypothesis that oxidative injury contributes to the pathogenesis of ARMD and that these modifications may have a critical role in drusen formation.
In 30 probands with a diagnosis of basal laminar drusen maculopathy, Boon et al. (2008) found the tyr402-to-his variant of the CFH gene, encoding complement factor H (134370.0008), in 48% of alleles. They found compound heterozygosity in affected members of 5 families for Y402H and another CFH mutation. Boon et al. (2008) concluded that their findings strongly supported a recessive disease model in a subgroup of patients with basal laminar drusen. In these families, individuals develop drusen when they carry a CFH mutation on 1 allele and the Y402H variant on the other. The presence of a CFH mutation in the absence of the Y402H variant, however, might contribute to the development of age-related macular degeneration at a later age.
Bok, D. New insights and new approaches toward the study of age-related macular degeneration. (Commentary) Proc. Nat. Acad. Sci. 99: 14619-14621, 2002. [PubMed: 12419853] [Full Text: https://doi.org/10.1073/pnas.242607899]
Boon, C. J. F., Klevering, B. J., Hoyng, C. B., Zonneveld-Vrieling, M. N., Nabuurs, S. B., Blokland, E., Cremers, F. P. M., den Hollander, A. I. Basal laminar drusen caused by compound heterozygous variants in the CFH gene. Am. J. Hum. Genet. 82: 516-523, 2008. [PubMed: 18252232] [Full Text: https://doi.org/10.1016/j.ajhg.2007.11.007]
Crabb, J. W., Miyagi, M., Gu, X., Shadrach, K., West, K. A., Sakaguchi, H., Kamei, M., Hasan, A., Yan, L., Rayborn, M. E., Salomon, R. G., Hollyfield, J. G. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc. Nat. Acad. Sci. 99: 14682-14687, 2002. [PubMed: 12391305] [Full Text: https://doi.org/10.1073/pnas.222551899]
Deutman, A. F., Jansen, L. M. A. A. Dominantly inherited drusen of Bruch's membrane. Brit. J. Ophthal. 54: 373-382, 1970. [PubMed: 5448127] [Full Text: https://doi.org/10.1136/bjo.54.6.373]
Evans, P. J. Five cases of familial retinal abiotrophy. Trans. Ophthal. Soc. U.K. 70: 96, 1950.