Aims: Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic analysis is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases. The Arg 345 Trp mutation on exon 10 of the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene causes two clinical phenotypes of early onset drusen (Doyne honeycomb retinal dystrophy andMalattia Leventinese), yet does not appear to be involved in other early onset drusen phenotypes or typical AMD. We wished to ascertain the involvement of the EFEMP1 gene in our population of sporadic and familial subjects presenting with early onset drusen and their affected relatives. Methods. Individuals presenting with drusen/endstage maculopathy at 60 years or under were identified from retinal clinics in Melbourne. All available first-and second degree relatives were also examined. In all, 116 ethnically matched controls were collected from the same community for comparison. Results. Single stranded conformational polymorphism( SSCP) analysis and subsequent sequencing revealed four previously described and three novel sequence variations. Most occurred at similar frequencies in the case and control populations andwere not thought to be disease associated. Conclusion. The term early onset drusen encompasses a wide range of phenotypes and our findings indicate that it is likely thatmore than one gene is involved in its causation. It is essential that these clinical phenotypes are well described and categorised to allow greater possibility of success in the search for other disease genes. Aims: Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic investigate is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases. The Arg 345 Trp mutation on exon 10 of the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) genes causes two clinical phenotypes of early onset drusen (Doyne honeycomb retinal dystrophy and Malattia leventinese) , yet does not appear to be involved in other early onset drusen phenotypes or typical AMD. We wished to ascertain the involvement of the EFEMP1 gene in our population of sporadic and familial subjects presenting with early onset drusen and their affected relatives. Methods. Individuals presenting with drusen / endstage maculopathy at 60 years or under were identified from retinal clinics in Melbourne. All availab le first-and second degree relatives were also examined. In all, 116 ethnically matched controls were collected from the same community for comparison. Results. Single stranded conformational polymorphism (SSCP) analysis and subsequent sequencing revealed four previously described and three novel sequence variations. Most occurred at similar frequencies in the case and control populations and we not not thought to be disease associated. It is essential that these clinical phenotypes are well described and categorized to allow greater possibility of success in the search for other disease genes.