GENEALOGY, NATURAL-HISTORY, AND PHENOTYPE OF ALSTROM-SYNDROME IN A LARGE ACADIAN KINDRED AND 3 ADDITIONAL FAMILIES

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 assessm ent, The affected subjects come from 5 nuclear families within this ki ndred, The phenotype includes early childhood retinopathy, progressive sensorineural hearing loss, truncal obesity, and acanthosis nigricans , In addition, hyperinsulinemia and hypertriglyceridemia with normal c holesterol levels were observed in most affected individuals tested, N on-insulin dependent diabetes mellitus and growth retardation appear t o be age-related manifestations that occur post-adolescence. Younger a ffected children are not overtly hyperglycemic and are normal or above average height for age, Although the AS patients in kindred 1 presuma bly carry the same mutation, many manifestations of the disease are va riable, For example, of the 8 children in the Acadian kindred, 4 have scoliosis, 2 have had infantile cardiomyopathy, 2 are hypothyroid, 1 h as had hepatic dysfunction and is hypertensive, and 4 have developed a sthma, Seven subjects described in this kindred exhibit developmental delay, One additional manifestation not described widely in the litera ture, advanced bone age, was observed in all subjects tested. The clin ical data from this large Acadian kindred, together with information o btained from 4 additional AS patients in 3 unrelated kindreds, confirm and extend clinical observations previously described, In addition, t he Acadian kindred with multiple affected individuals, probably arisin g from a common founder, should allow for identification of the chromo somal localization of a gene causing AS. (C) 1997 Wiley Liss, Inc.