New Alström syndrome phenotypes based on the evaluation of 182 cases.
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.
Marshall
Jan D
JD
The Jackson Laboratory, Bar Harbor, ME 04609, USA. jdm@jax.org
Bronson
Roderick T
RT
Collin
Gayle B
GB
Nordstrom
Anne D
AD
Maffei
Pietro
P
Paisey
Richard B
RB
Carey
Catherine
C
Macdermott
Seamus
S
Russell-Eggitt
Isabelle
I
Shea
Sarah E
SE
Davis
Judy
J
Beck
Sebastian
S
Shatirishvili
Gocha
G
Mihai
Cristina Maria
CM
Hoeltzenbein
Maria
M
Pozzan
Giovanni Battista
GB
Hopkinson
Ian
I
Sicolo
Nicola
N
Naggert
Jürgen K
JK
Nishina
Patsy M
PM
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