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BackgroundThe past few decades have witnessed a tremendous development in the field of genetics. The implementation of next generation sequencing (NGS) technologies revolutionized the field of molecular biology and made the genetic information accessible at a large scale. However, connecting a rare genetic variation to a complex phenotype remains challenging. Indeed, identifying the cause of a genetic disease requires a multidisciplinary approach, starting with the establishment of a clear phenotype with a detailed family history and ending, in some cases, with functional assays that are crucial for the validation of the pathogenicity of a mutation.MethodsTwo hundred Lebanese patients, presenting a wide spectrum of genetic disorders (neurodevelopmental, neuromuscular or metabolic disorders, etc.), sporadic or inherited, dominant or recessive, were referred, over the last three and a half years, to the Medical Genetics Unit (UGM) of Saint Joseph University (USJ). In order to identify the genetic basis of these diseases, Whole Exome Sequencing (WES), followed by a targeted analysis, was performed for each case. In order to improve the genetic diagnostic yield, WES data, generated during the first 2 years of this study, were reanalyzed for all patients who were left undiagnosed at the genetic level. Reanalysis was based on updated bioinformatics tools and novel gene discoveries.ResultsOur initial analysis allowed us to identify the specific genetic mutation causing the disease in 49.5% of the cases, in line with other international studies. Repeated WES analysis enabled us to increase the diagnostics yield to 56%.ConclusionThe present article reports the detailed results of both analysis and pinpoints the contribution of WES data reanalysis to an efficient genetic diagnosis. Lessons learned from WES reanalysis and interpretation are also shared.

FB aspiration is a serious problem. A high index of suspicion is required in health care providers (ENT, pediatricians and family physicians). Physician and especially parental education are the main guarantors of significantly reduced morbidity and mortality in this pathology.

ABSTRACT. Cogan's syndrome is a rare, chronic inflammatory disorder that typically targets the eyes and vestibuloauditory apparatus, but it may also involve other organs. Three pediatric cases of Cogan's syndrome (ages 5, 13, and 18 years) are reported with long-term follow-up and complete and regular cochleovestibular functional evaluation and ophthalmologic and neurologic examinations. One case was a typical form (characterized by an interstitial keratitis and cochleovestibular impairment), whereas the other 2 cases were atypical forms with uveitis and polyarthritis. In all 3 cases, the first clinical sign was nonspecific eye redness misdiagnosed as a banal conjunctivitis, initially or secondarily associated with bilateral endocochlear sensorineural hearing loss and complete bilateral peripheral vestibular deficit. During the acute phase, early steroid treatment (prednisone, 1 mg/kg/day) was effective in treating the ocular lesions (3 of 3 cases) and improving hearing (2 of 3 cases) but less effective for the vestibular loss (2 of 3 cases). Adverse effects and dependence on the steroid occurred in 2 cases, and immunosuppressive drugs were necessary to avoid recurrences in 1 case. Over the longterm, the disease was controlled in 2 cases but continued to progress in the other. Cogan's syndrome in childhood should be suspected in cases of conjunctivitis associated with inner-ear symptoms; a prompt steroid treatment can avoid progressive impairment of multiple sensorineural functions (vision, balance, hearing). Long-term management involves limiting disease recurrences by adaptive therapies, screening for complications (aortitis in particular), and planning rehabilitation for the sensorial deficits. Pediatrics 2002;109(2). URL: http://www. pediatrics.org/cgi/content/full/109/2/e38; children, Cogan's syndrome, sudden hearing loss, imbalance, vertigo, conjunctivitis.ABBREVIATIONS. EVAR, earth vertical axis rotation; OVAR, off vertical axis rotation test; VOR, vestibuloocular responses; SNHL, sensorineural hearing loss; NSAID, nonsteroidal antiinflammatory drugs; MRI, magnetic resonance imaging; EBV, Epstein-Barr virus. C ogan's syndrome is a relatively rare inflammatory disease characterized by nonsyphilitic ocular interstitial keratitis associated with sudden hearing loss and vestibular impairment. However, its early diagnosis and treatment with steroids can prevent loss of inner-ear sensorial function and limit ophthalmologic aftereffects. In 1934, Morgan and Baumgartner 1 published the first case of the syndrome. In 1945, Cogan 2 published the full description of the syndrome as an inner-ear disorder in its typical form. Several authors later reported atypical forms 3,4 that differed from the typical presentation by the type of ocular lesions, which can include superficial keratitis, scleritis, episcleritis, iritis, or choroiditis, as well as variable hearing impairment and often systemic inflammation. 5 Cogan's syndrome is generally considered an autoimmune disease despite the frequent lack of direct immunologic...