New Alstrom syndrome phenotypes based on the evaluation of 182 cases

被引:222
作者
Marshall, JD
Bronson, RT
Collin, GB
Nordstrom, AD
Maffei, P
Paisey, RB
Carey, C
MacDermott, S
Russell-Eggitt, I
Shea, SE
Davis, J
Beck, S
Shatirishvili, G
Mihai, CM
Hoeltzenbein, M
Pozzan, GB
Hopkinson, I
Sicolo, N
Nagget, JK
Nishina, PM
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
[2] Univ New Hampshire, Dept Sociol, Durham, NH 03824 USA
[3] Univ Padua, Sch Med, I-35100 Padua, Italy
[4] Torbay Hosp, Torquay, England
[5] Great Ormond St Hosp Sick Children, Dept Paediat Ophthalmol, London WC1N 3JH, England
[6] Izaak Walton Killam Hlth Ctr, Dept Dev Pediat, Halifax, NS, Canada
[7] Calif Digest Dis Ctr, Fresno, CA USA
[8] Clin Genet Ctr, Mol Biol Lab, Oporto, Portugal
[9] Minist Labour Hth & Social Affairs Georgia, Program Rare Dis, Tbilisi, Georgia
[10] Spitalul Clin Urgenta, Clin Pediat Compartimental Diabet Nutr Boli Metab, Constanta, Romania
[11] Max Planck Inst Mol Genet, Berlin, Germany
[12] Royal Free Univ Coll Med Sch, Dept Primary Care & Populat Sci, London, England
[13] UCL, Rayne Inst, Dept Med, Cardiovasc Genet Unit, London WC1E 6BT, England
关键词
D O I
10.1001/archinte.165.6.675
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Alstrom 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 Alstrom 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 rnellitus 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 Alstrom syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.
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页码:675 / 683
页数:9
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