RESUMO
PURPOSE: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. METHODS: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. RESULTS: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children; 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). CONCLUSIONS: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.
Assuntos
Actinas/genética , Colágeno Tipo XI/genética , Conexina 26/genética , Surdez/genética , Perda Auditiva Neurossensorial/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Adulto , Criança , Pré-Escolar , Surdez/diagnóstico , Surdez/patologia , Exoma/genética , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/patologia , Humanos , Masculino , Mutação/genética , Patologia Molecular , Linhagem , Sequenciamento do Exoma/normasRESUMO
Palinopsia is defined as the persistence or reappearance of images after cessation of the visual stimulus. One patient presented episodes of palinopsia after the functional loss of the 3 semicircular canals of the right ear while the otolithic function was preserved. None of classical causes was identified in this patient, intoxications, brain tumors, migraines, psychiatric disorders, etc. For a movement to be perceived as a single event, central processes of temporal integration are necessary to correct the shift between the rapid vestibular information, and the slow visual information. However, it has been shown on animal models that vestibular inputs are slower than normal in case of peripheral deafferentation limited to the canalar function with preservation of the otolithic function, which is the case in this patient. Therefore, we hypothesize that episodes of palinopsia he presents result from the fact that temporal integration processes do not take into account the slower than normal vestibular information due to the peripheral disorder and continue to slow it down. Thus, the patient keeps the visual image in memory until the late arrival of the vestibular information.
RESUMO
We present a patient suffering from persistence of images after cessation of the visual stimulus, a phenomenon called palinopsia. As none of classical causes existed in this patient, we hypothethized that the phenomenon is related to the particular dysfunction of his right inner ear associating a canalar deficit with a preserved otolithic function. In such a situation, the vestibular inputs are slower than normal. Therefore, palinopsia could result from an abnormal temporal integration of visual and vestibular informations.
Nous présentons un patient souffrant de la persistance des images après la cessation du stimulus visuel, un phénomène appelé « palinopsie ¼. Comme aucune des causes classiques n'existait chez ce patient, nous avons émis l'hypothèse que le phénomène soit lié au dysfonctionnement particulier de son oreille interne droite associant un déficit canalaire à une fonction otolithique préservée. Dans une telle situation, les entrées vestibulaires sont plus lentes que la normale. Par conséquent, les épisodes de palinopsie pourraient résulter d'une intégration temporelle anormale des informations visuelles et vestibulaires.
