SANDO syndrome in a cohort of 107 patients with CPEO and mitochondrial DNA deletions.

Abstract

OBJECTIVE:

The sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) syndrome is a subgroup of mitochondrial chronic progressive external ophthalmoplegia (CPEO)-plus disorders associated with multiple mitochondrial DNA (mtDNA) deletions. There is no systematic survey on SANDO in patients with CPEO with either single or multiple large-scale mtDNA deletions.

METHODS:

In this retrospective analysis, we characterised the frequency, the genetic and clinical phenotype of 107 index patients with mitochondrial CPEO (n=66 patients with single and n=41 patients with multiple mtDNA deletions) and assessed these for clinical evidence of a SANDO phenotype. Patients with multiple mtDNA deletions were additionally screened for mutations in the nuclear-encoded POLG, SLC25A4, PEO1 and RRM2B genes. The clinical, histological and genetic data of 11 patients with SANDO were further analysed.

RESULTS:

None of the 66 patients with single, large-scale mtDNA deletions fulfilled the clinical criteria of SANDO syndrome. In contrast, 9 of 41 patients (22%) with multiple mtDNA deletions and two additional family members fulfilled the clinical criteria for SANDO. Within this subgroup, multiple mtDNA deletions were associated with the following nuclear mutations: POLG (n=6), PEO1 (n=2), unidentified (n=2). The combination of sensory ataxic neuropathy with ophthalmoparesis (SANO) was observed in 70% of patients with multiple mtDNA deletions but only in 4% with single deletions. The combination of CPEO and sensory ataxic neuropathy (SANO, incomplete SANDO) was found in 43% of patients with multiple mtDNA deletions but not in patients with single deletions.

CONCLUSION:

The SANDO syndrome seems to indicate a cluster of symptoms within the wide range of multisystemic symptoms associated with mitochondrial CPEO. SANO seems to be the most frequent phenotype associated with multiple mtDNA deletions in our cohort but not or is rarely associated with single, large-scale mtDNA deletions.

• Authors: Frank Hanisch, Malte Kornhuber, Charlotte L Alston, Robert W Taylor, Marcus Deschauer, Stephan Zierz
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 86 Issue 6 Pg. 630-4 (Jun 2015) ISSN: 1468-330X [Electronic] England
• PMID: 25143630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• DNA, Mitochondrial
• Mitochondrial Proteins
• DNA Polymerase gamma
• DNA-Directed DNA Polymerase
• POLG protein, human
• DNA Helicases
• TWNK protein, human

Topics

• Adolescent
• Adult
• Age of Onset
• Aged
• Biopsy
• Child
• Cohort Studies
• DNA Helicases (genetics)
• DNA Polymerase gamma
• DNA, Mitochondrial (genetics)
• DNA-Directed DNA Polymerase (genetics)
• Dysarthria (epidemiology, genetics)
• Female
• Gene Deletion
• Hereditary Sensory and Motor Neuropathy (epidemiology, genetics)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Mitochondrial Proteins (genetics)
• Muscle, Skeletal (pathology)
• Ophthalmoplegia (epidemiology, genetics)
• Ophthalmoplegia, Chronic Progressive External (epidemiology, genetics)
• Retrospective Studies
• Syndrome
• Young Adult