Clinical Phenotype and Genetic Features of a Pair of Chinese Twins with Kearns–Sayre Syndrome

Abstract

Kearns-Sayre Syndrome (KSS) is a severe mitochondrial disorder involving the central nervous system, eyes, ears, skeletal muscles, and heart. The mitochondrial DNA (mtDNA) rearrangements, especially the deletions, are present in almost all KSS patients and considered as the disease-causing factor. However, the size and position of mtDNA deletions are distinct in different individuals. In this study, we report the case of a pair of Chinese twins with KSS. The twin patients revealed typical KSS clinical symptoms, including heart block, bilateral sensorineural hearing loss, progressive external ophthalmoplegia, exercise intolerance, proximal limb weakness, and endocrine disorders. Using long-range polymerase chain reactions (long-range PCR) and nextgeneration sequencing (NGS), the genetic features of the twin patients were investigated. A large 6600 bp mtDNA deletion, ranging from position 8702 to 15,302, was detected in both patients. To our knowledge, this kind of mtDNA deletion has never been described previously. Our study enriched the mutation spectrum of KSS and showed that NGS is a powerful tool for detecting mtDNA large variants.

Kearns–Sayre syndrome with a novel large-scale deletion: a case report

“…The size of the long-range deletions described in the literature fluctuate from 2 to 10 kb, and the size and location of the mitochondrial deletions vary from individual to individual. However, studies have reported a ‘common deletion’ of 4.9 kb (4977 bp; m.8470–13446del) between ATPase 8 and ND5 genes in one-third of KSS patients [ 21 , 22 ]. In our study, the long-range PCR study identified a 7652-bp deletion from nucleotides 6341 to 13,993 of the mtDNA, which is accepted as the immediate cause of our patient’s multisystem mitochondrial disorder.…”

“…At the same time, because of the disparity of mtDNA rearrangement in additional populations, the constant advances of biochemical markers and expansion of genotypes of mitochondrial disorders pose a challenge. In other words, the analysis mtDNA rearrangement not only is crucial for broadening the alterant spectrum of disease but also vital to acknowledge the connection between mtDNA abnormality and clinical manifestations [ 22 ]. Defects in any of the numerous mitochondrial pathways can cause mitochondrial diseases and further induce pathological consequences.…”

Electrolyte Disorders in Mitochondrial Cytopathies: A Systematic Review

“…In addition to investigating the co-occurrence of specific electrolyte abnormalities, we also examined which pathophysiologic mechanisms were reported by the authors to explain their findings (Table 2). Commonly reported mechanisms include hypoparathyroidism causing hypocalcemia with hyperphosphatemia (55 patients), 14,24,[32][33][34][35][36][37][38][39] proximal tubulopathies causing metabolic acidosis, hyponatremia and/or hyperkalemia (46 patients), 10,19,[40][41][42][43][44][45] and tubulopathies affecting distal segments (33 patients and one large family). 4,5,11,16,18,20,[46][47][48][49] In line with the frequent reporting of tubulopathies, 72 patients were identified in whom reported urinary electrolytes provided evidence for renal electrolyte wasting.…”

Inherited causes of combined vision and hearing loss: clinical features and molecular genetics

“…Kearns-Sayre syndrome (KSS) is a rare multi-system mitochondrial DNA (mtDNA) deletion syndrome [109,110], characterised by chronic progressive external ophthalmoplegia, pigmentary retinopathy and heart block [110]. Several other features have been reported, such as sensorineural hearing loss, cerebellar ataxia, endocrine disorders, cognitive impairment, and increased levels of cerebrospinal fluid protein [19,[111][112][113][114]. A study by Kornblum et al assessed the nature of the hearing loss in 17 affected individuals, 10 of whom were found to have hearing impairment.…”