TY - JOUR
T1 - Respiratory manifestations in 38 patients with Alström syndrome
AU - Boerwinkle, Caroline
AU - Marshall, Jan D.
AU - Bryant, Joy
AU - Gahl, William A.
AU - Olivier, Kenneth N.
AU - Gunay-Aygun, Meral
N1 - Funding Information:
The authors thank Alström syndrome International for their extensive support and the individuals with AS and their families who generously participated in this investigation. This research was supported by the Intramural Research Programs of the National Human Genome Research Institute, (NHGRI), the National Institute of Allergy and Infectious Diseases, and the National Heart Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD. The Genetic Disorders of Mucociliary Clearance (U54HL096458) is a part of the NCATS Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, funded through a collaboration between NCATS and NHLBI.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Alström syndrome
KW - bronchiectasis and primary ciliary dyskinesia
KW - ciliopathy
KW - developmental biology
KW - nitric oxide
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UR - http://www.scopus.com/inward/citedby.url?scp=85007487709&partnerID=8YFLogxK
U2 - 10.1002/ppul.23607
DO - 10.1002/ppul.23607
M3 - Article
C2 - 28029746
AN - SCOPUS:85007487709
VL - 52
SP - 487
EP - 493
JO - Pediatric Pulmonology
JF - Pediatric Pulmonology
SN - 8755-6863
IS - 4
ER -