Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related?) neurocristopathy?

Abstract

The Authors report on a patient with Kearns-Sayre syndrome, large mtDNA deletion (7/kb), facial abnormalities and severe central nervous system (CNS) white matter radiological features, commonly attributed to spongy alterations. The common origin from neural crest cell (NCC) of facial structures (cartilagineous, osseous, vascular and of the peripheral nervous system) and of peripheral glia and partially of the CNS white matter are underlined and the facial and glial abnormalities are attributed to the abnormal reproduction/migration of NCC. In this view, the CNS spongy alterations in KSS may be not only a dystrophic process (leukodystrophy) but also a dysplastic condition (leukodysplasia). The Authors hypothesize that the symptoms may be related to mtDNA mutations associated to NCC nuclear gene abnormality.

Mitochondrial Disease and Hearing Loss in Children: A Systematic Review

“…The search strategy yielded 984 records (Fig. 1 and Table II), of which 23, detailing a total of 75 individuals with genetically proven MD and sufficient data on hearing loss, were eligible for final inclusion and analysis 10,16,25–45 …”

“…1 and Table II ), of which 23, detailing a total of 75 individuals with genetically proven MD and sufficient data on hearing loss, were eligible for final inclusion and analysis. 10 , 16 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45…”

The Genetic Cause of Kearns-Sayre Syndrome Determines Counselling and Outcome of These Patients

“…The diagnosis of KSS is established upon the phenotype if there is presence of all 3 cardinal features (progressive external ophthalmoplegia, onset < 20 years, pigmentary retinopathy) and of at least 1 of the additional features (hypoacusis, ataxia, peripheral nervous system [PNS] involvement, short stature, growth hormone deficiency, lactic acidosis, dysmorphism, hypoparathyroidism, emesis, aortic insufficiency, subaortic septum hypertrophy, right bundle-branch block, double vision, or white matter lesions). 2 Thus, Ramcharan's case does not entirely fulfil Berio's diagnostic criteria.…”

Progressive external ophthalmoplegia

“…Вовлечение ЦНС определяется изменениями на МРТ головного мозга, которые могут включать гиперинтенсивные сигналы в режиме FLAIR в стволе головного мозга, базальных ганглиях, таламусе и белом веществе больших полушарий и мозжечка с развитием выраженной лейкоэнцефалопатии и диффузной атрофии вещества головного мозга. Кроме того, региональные нарушения метаболизма в клетках головного мозга можно определить с помощью метода МР-спектроскопии [38,39]. Однако нейровизуализация не может быть единственным диагностическим методом, так как находки на МРТ не являются достаточно чувствительными и специфичными, чтобы войти в диагностические критерии при митохондриальных заболеваниях, но они могут помочь определить выраженность поражения ЦНС [38].…”