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Inherited retinal dystrophies (IRDs) are a major cause of childhood blindness. Timely diagnosis requires a high level of clinical suspicion from both neurologists and ophthalmologists and is increasingly important given recent advancements in gene therapy. We focused our study on genotype-phenotype associations in very early-onset forms of retinal dystrophy, the least well characterized and most challenging diagnostic subgroup. From January 12, 2015 to March 31, 2017, we prospectively performed whole exome sequencing targeted on the phenotype of non-syndromic IRDs and phenotype characterization in a cohort of 68 children affected by very early-onset inherited retinal dystrophies, defined by the onset before five years of age. Phenotype parameters included age at onset, clinical presentation, ophthalmic evaluation, electrophysiological patterns and clinical course. A genetically confirmed diagnosis was achieved in 50 out of 60 (83%) families. The median age at onset was 4 months (<6 m in 70%, < 2 y in 82% of the cases). Clinical presentation was associated with visual loss and nystagmus in the majority of patients. Three (CNGB3, CNGA3 and CACNA1F) out of 22 genes considered pathogenic in the cohort, accounted for 51% of all IRD's, all within the class of stationary IRDs. This study reports on the largest cohort of very early-onset retinal dystrophies, including a description of electroretinography patterns. The electro-clinical phenotype coupled with genetic diagnosis provided additional clues for child neurologists dealing with low vision and nystagmus in infancy. A high level of clinical suspicion improves the diagnosis with important implications for the future of the affected child. • Diagnosis of low vision in infancy bridges and challenges paediatric neurology and ophthalmology. • Inherited retinal dystrophies are major causes of inherited childhood blindness. • Very early onset forms of retinal dystrophy are the least well characterized and most difficult diagnostic subgroup. • Exome analysis performed in clinically focused tiered fashion allowed a detection rate of 82%, the highest reported to date. • We propose an electro-clinical diagnostic algorithm for low vision and nystagmus in infancy. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships. Methods: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ⩾70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for ⩾3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV1/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey. Results: After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects ⩾50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. Conclusions: Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality. [ABSTRACT FROM AUTHOR]