title: Respiratory manifestations in 38 patients with Alström syndrome.
abstract: Alström syndrome (AS) is a rare, multi-system condition characterized by retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, hypertriglyceridemia, cardiomyopathy, hepatorenal disease, and recurrent respiratory infections. It belongs to a group of genetic disorders known as primary ciliopathies, which includes autosomal dominant and recessive polycystic kidney diseases, as well as Joubert and Bardet-Biedl syndromes. Prior studies have suggested phenotypic overlap between primary ciliopathies affecting the non-motile, sensory cilia, and primary ciliary dyskinesia (PCD), a motile ciliopathy characterized by respiratory tract disease.
  
  
  
  We describe the burden of oto-sino-pulmonary disease in 38 individuals with AS and examines the degree of clinical overlap between PCD and AS. Evaluation at the NIH Clinical Center included clinical examination, chest imaging, and clinical history surveys, as well as measurement of nasal nitric oxide (nNO) in nine patients.
  
  
  
  Recurrent otitis media was ubiquitous in the AS cohort (92%) with 50% requiring pressure equalization tube placement. A history of bronchitis/pneumonia and sinusitis was reported in 61% and 50% of individuals, respectively. PCD-characterizing symptoms (laterality defects, unexplained neonatal respiratory distress, year-round nasal congestion, and wet cough) were far less prevalent in the AS cohort compared to PCD, and the average nNO production in the AS cohort was 232 ± 57.1 nl/min compared to a cut-off of <77 nl/min for PCD.
  
  
  
  These data suggest that the oto-sino-respiratory complications in AS are prominent enough to warrant increased clinical attention, but significantly impaired respiratory cilia function as seen in PCD is unlikely in AS. (www.clinicaltrials.gov, trial NCT00068224) Pediatr Pulmonol. 2017;52:487-493. © 2016 Wiley Periodicals, Inc.
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Boerwinkle
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine.|Alström Syndrome International, Mt Desert, Maine.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland.
authors.forename: Joy
authors.initials: J
authors.lastname: Bryant
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.|National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland.
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D056769:Alstrom Syndrome / Q000175:diagnosis* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002925:Ciliary Motility Disorders / Q000503:physiopathology; D003371:Cough / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009316:National Institutes of Health (U.S.); D015995:Prevalence; D012720:Severity of Illness Index; D014481:United States
keywords:  developmental biology; Alström syndrome; bronchiectasis and primary ciliary dyskinesia; ciliopathy; nitric oxide