Genealogy, natural history, and phenotype of Alström syndrome in a large Acadian kindred and three additional families

Am J Med Genet. 1997 Dec 12;73(2):150-61. doi: 10.1002/(sici)1096-8628(19971212)73:2<150::aid-ajmg9>3.0.co;2-y.

Abstract

We describe a large Acadian kindred including 8 Alstrom Syndrome (AS) patients, with an age range of 4 to 26 at the time of clinical assessment. The affected subjects come from 5 nuclear families within this kindred. The phenotype includes early childhood retinopathy, progressive sensorineural hearing loss, truncal obesity, and acanthosis nigricans. In addition, hyperinsulinemia and hypertriglyceridemia with normal cholesterol levels were observed in most affected individuals tested. Non-insulin dependent diabetes mellitus and growth retardation appear to be age-related manifestations that occur post-adolescence. Younger affected children are not overtly hyperglycemic and are normal or above average height for age. Although the AS patients in kindred 1 presumably carry the same mutation, many manifestations of the disease are variable. For example, of the 8 children in the Acadian kindred, 4 have scoliosis, 2 have had infantile cardiomyopathy, 2 are hypothyroid, 1 has had hepatic dysfunction and is hypertensive, and 4 have developed asthma. Seven subjects described in this kindred exhibit developmental delay. One additional manifestation not described widely in the literature, advanced bone age, was observed in all subjects tested. The clinical data from this large Acadian kindred, together with information obtained from 4 additional AS patients in 3 unrelated kindreds, confirm and extend clinical observations previously described. In addition, the Acadian kindred with multiple affected individuals, probably arising from a common founder, should allow for identification of the chromosomal localization of a gene causing AS.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Abnormalities, Multiple / blood
  • Abnormalities, Multiple / ethnology
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Acanthosis Nigricans / blood
  • Acanthosis Nigricans / ethnology
  • Acanthosis Nigricans / genetics
  • Acanthosis Nigricans / physiopathology
  • Adolescent
  • Age Determination by Skeleton
  • Child
  • Child, Preschool
  • Female
  • Genealogy and Heraldry*
  • Hearing Loss, Sensorineural / blood
  • Hearing Loss, Sensorineural / ethnology
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • Heterozygote
  • Humans
  • Male
  • Nova Scotia
  • Obesity / blood
  • Obesity / ethnology
  • Obesity / genetics*
  • Obesity / physiopathology
  • Pedigree
  • Phenotype
  • Retinitis Pigmentosa / blood
  • Retinitis Pigmentosa / ethnology
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / physiopathology
  • Syndrome