title: New Alström syndrome phenotypes based on the evaluation of 182 cases.
abstract: BACKGROUND
  Alström syndrome is a recessively inherited genetic disorder characterized by congenital retinal dystrophy that leads to blindness, hearing impairment, childhood obesity, insulin resistance, and type 2 diabetes mellitus. We provide new details on cardiologic, hepatic, gastrointestinal, urologic, pulmonary, and neurobehavioral phenotypes in Alström syndrome and describe the histopathologic findings in 5 individuals.
  
  
  METHODS
  We obtained data on 182 patients from clinical examinations, medical record reviews, standardized questionnaires, and personal interviews with physicians and parents.
  
  
  RESULTS
  Dilated cardiomyopathy occurred in 60% of patients. Age at onset was either during infancy, often before vision disturbances were noted, or in adolescence or adulthood. There is a risk of recurrence of infantile cardiomyopathy. Hyperinsulinemia (92%) developed in early childhood and progressed to type 2 diabetes mellitus in 82% of those older than 16 years. Hypertriglyceridemia (54%) precipitated pancreatitis in 8 patients. Urologic dysfunction and gastrointestinal disturbances occurred in 48% and 35% of patients, respectively. Fifty-three percent of patients had persistent pulmonary symptoms. Neurologic symptoms in 20% of patients included clonic tic and absence seizures. Developmental motor or language delays were observed in 46% of patients. Fibrotic infiltrations of multiple organs, that is, kidney, heart, liver, lung, urinary bladder, gonads, and pancreas, were observed.
  
  
  CONCLUSIONS
  The wide-ranging and complex spectrum of phenotypes reported herein broadens those previously described for Alström syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA. jdm@jax.org
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Anne D
authors.initials: AD
authors.lastname: Nordstrom
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
authors.forename: Richard B
authors.initials: RB
authors.lastname: Paisey
authors.forename: Catherine
authors.initials: C
authors.lastname: Carey
authors.forename: Seamus
authors.initials: S
authors.lastname: Macdermott
authors.forename: Isabelle
authors.initials: I
authors.lastname: Russell-Eggitt
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Shea
authors.forename: Judy
authors.initials: J
authors.lastname: Davis
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beck
authors.forename: Gocha
authors.initials: G
authors.lastname: Shatirishvili
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Mihai
authors.forename: Maria
authors.initials: M
authors.lastname: Hoeltzenbein
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Pozzan
authors.forename: Ian
authors.initials: I
authors.lastname: Hopkinson
authors.forename: Nicola
authors.initials: N
authors.lastname: Sicolo
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D007006:Hypogonadism / Q000453:epidemiology / Q000503:physiopathology; D007223:Infant; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000503:physiopathology; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000453:epidemiology / Q000503:physiopathology; D013577:Syndrome