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

Longitudinal study of the early electroretinographic changes in Alström's syndrome.

We obtained serial electroretinograms in four patients aged between 6 months and 5 years with Alström's syndrome and studied the early stages of the severe retinopathy that is characteristic of that disease. The weak electroretinographic signals found at age 6 months demonstrate a severe early cone dysfunction; one year later the cone activity is undetectable. The rod component of the electroretinogram is initially normal but can rapidly deteriorate to become undetectable as early as 5 years of age. These unusual electroretinographic findings are pathognomonic of Alström's syndrome and different from other cone-rod dystrophies or other syndromes with similar phenotypes such as Bardet-Biedl, Laurence-Moon, and Cohen syndromes.

The electroretinographic diagnosis of the incomplete form of congenital stationary night blindness.

Fifteen patients with the incomplete form of congenital stationary night blindness (iCSNB) were reviewed to better characterize their electroretinographic (ERG) findings in view of differential diagnosis with other retinal conditions also presenting with negative bright-flash ERG responses. In all 15 patients, in dark-adapted conditions, the bright-flash ERG response had a normal a-wave followed by a subnormal b-wave. Oscillatory potentials (OPs) observed on the ascending limb of the b-wave, although delayed in implicit time, were of large amplitude. The response to a long-wavelength stimulus showed cone-related components and some well-delineated OPs. On the other hand, the photopically elicited cone responses were strongly abnormal, with a subnormal a-wave followed by a barely recordable b-wave. No OPs could be elicited under photopic conditions. The cone related components and the OP characteristics clearly distinguish iCSNB from the complete form of CSNB and other retinal conditions presenting with minimal fundus abnormalities but with negative bright-flash ERG responses, such as found in Duchenne muscular dystrophy and Aland Island eye disease. The severely abnormal post-synaptic components in the photopic recordings contrast with the well-differentiated cone activity evoked in scotopic conditions. We propose a cone system that does not respond optimally under the normal operating range (photopic) but rather under mesopic or scotopic conditions. In spite of the severe cone-ERG deficits, visual acuity was only slightly reduced. We propose that the defect, which interferes marginally with the neuronal flow of information, lies in the structures responsible for the building of the b-wave.