Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Abstract

PURPOSE. In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012.METHODS. Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided.RESULTS. Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population.CONCLUSIONS. Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

“…As a result, a full characterization of the nation-based LHON cohort including diagnosed cases and family members was obtained. 13 All identified patients and their family members assigned a Civil Registration number are included. Individuals were registered as either (1) subjects with LHON or (2) their brothers and sisters and first-degree relatives in the ascending maternal line without reported manifest LHON.…”

“…The median age at onset in Denmark has previously been shown to be 25 for males and 33 for females. 13 Therefore, individuals most likely at age 30 will be influenced by the genetic or environmental factors determining the penetrance for LHON mutations. All family members were relatives in the ascending female line and therefore probably harbored the mutation, however possibly with individual differences in mutational load, which was not accounted for.…”

Mitochondrial DNA variation of Leber’s Hereditary Optic Neuropathy (LHON) in Western Siberia

“…multiple sclerosis) forms of LHON. Patients with LHON could have also been wrongly diagnosed as suffering from toxic amblyopia, tobacco-alcohol amblyopia, or optic neuritis(Rosenberg, Norby et al 2016). On the other hand, the problem is that patients do not now their family history.…”

Clinical Reasoning: A 10-year-old boy with bilateral vision loss

“…2 No epidemiologic studies have been carried out in the United States, but reports from northern Europe indicate the prevalence of LHON diagnosed by the 3 most common point mutations to be 1 in 31,000-54,000. [3][4][5][6] LHON is predominantly diagnosed in men (80%-90%) in the second and third decade of life, although cases in patients as young as 2 years and as old as 87 years at diagnosis have been documented. 2 The patient typically presents with painless, subacute vision loss in one eye, followed by sequential vision loss weeks later in the other eye.…”