Clinical characteristics of eight cases with Kearns-Sayre syndrome in children

Objective To analyze the clinical characteristics and the diagnostic methods of Kearns-Sayre syndrome(KSS) in children. Methods The clinical features including clinical manifestations, neurologic signs, cranial MRI, laboratory tests, common point mutations of the mtDNA and muscular pathology in 8 patients with KSS were retrospectively analyzed and the cases were followed-up. Results There were six males and two females in this study. The ages of onset ranged from 5 years 3 months to 13 years with the average age being 9 years 5 months. The disease course was from 1 month to 3 years with an average age of 1.5 years. Eight cases had ptosis in whom five had ptosis as the first symptom and four had both eyes affected at the same time. Two cases had ataxia as the first symptom, one of which had intelligence retrogression as the first symptom and three cases had double eyelid ptosis 1 month to 2.5 years after the onset. Two cases had diabetes mellitus and one case had Person syndrome before. All of 8 cases had ocular motor abnormalities and short stature in whom the height and weight were the tenth centile below the normal children of the same age. Six cases were found retinal pigmentary by ocular fundus examination. One case had no retinal pigmentary degeneration until 5 years in follow-up visit. All the cases had no optic atrophy. Six cases had cerebellar ataxia. Five cases had cardiac conduction block. Three cases were with complete or incomplete right bundle branch block at admission and developed to third-degree atrioventricular block from 1 year 7 months to 4 years respectively and died in follow-up visit. Two cases without cardiac conduction block when hospitalized were found to have first-degree atrioventricular block in 4 or 5 years follow-up. Six cases were found cerebrospinal fluid protein increased( 1 000 mg·L-1). In seven cases with urine amino acid/organic acid analysis,four were normal, three were with ketonuria. No mutation was found in mtDNA A3243G,A8344G,T8993G,T8993C,A1555G,G11778A screening. Eight cases with MRI examination showed a bilaterally symmetrical hypointense on T1 weighted image,hyperintense on T2 and high flair signal in white matter, mainly in the subcortical white-matter of frontal and parietal lobe and cerebellum white-matter. In two cases, splenium of corpus callosum was affected. In one case, posterior limb of internal capsule was affected. In six cases, brain stem was affected, mainly in deutocerebrum and dorsal part of pontine tegmentum. Thalamus was affected in three cases and basal ganglia was affected in four cases. Six cases of muscle pathology who accepted histochemical examination revealed RRFs. Eight cases were observed under the electronmicroscope subsarcolemmal accumulation of mitochondria and morphologic abnormalities of mitochondria. By using southern blot analysis, in the samples of muscle large fragment mtDNA deletion of 6 kb was existed in one case. In 6 cases followed-up from 2 to 5 years, three patients died and three patients′ course was slowly aggravatin. Conclusions KSS is rare in children. Clinical findings consist of bilateral ptosis, ophthalmoplegia, pigmentary retinopathy, cerebellar ataxia and cardiac conduction block. Clinical diagnosis can be made according to the clinical manifestation and muscle biopsy, and mtDNA deletion in muscle samples can confirm the diagnosis.