Kearns-Sayre Syndrome, KSS, Chronic Progressive Ophtalmoplegia, CPEO - POLG, PEO1, ANT1, POLG2, RRM2B, OPA1

Chronic progressive external opthalmoplegia (CPEO)

Clinical Features

The clinical picture is variable from isolated CPEO to KSS. Additional symptoms might be retinopathy, lactic acidosis, sensori-neuronal hearing loss, ataxia, cardiomyopathy or arrythmia, increased CSF protein and dementia. The onset of the disease is also variable (childhood to late adulthood). Another phenotypic variant of the disease is Pearson syndrome.

Genetic Information

KSS and CPEO are usually caused by single or multiple deletions of the mtDNA. Single mtDNA deletions are sporadic. Autosomal dominant (ANT1, Twinkle, POLG1, POLG2) or recessive (POLG1) mutations might be also present, these defects are usually associated with multiple deletion of the mtDNA.

Prevalence

In a study from North-Spain the prevalence of mtDNA deletions was 0,68 : 100 000.

In Germany the exact occurrence is not known yet. The frequency of all mitochondrial disease world-wide is ca. 1 : 3 000.

Diagnostic

Indication

CPEO or KSS

Method

1. Southern blot / long-range PCR for mtDNA deletion(s)

2. Mutation analysis of the entire coding and flanking intronic regions with intronic primers of the following genes: POLG1, Twinkle and ANT1 by direct DNA sequencing.

Sample Requirement

1. Southern blot / long-range PCR: DNA extracted from muscle (blood DNA is not informative!)

2. Mutation analysis: 2 - 4 ml of EDTA-blood

Duration

1. 1 - 2 weeks

2. 4 - 6 weeks

OMIM

530000 Kearns Sayre syndrome