Renal prognosis in Alport's and related syndromes: influence of the mode of inheritance

Progressive hereditary nephritis is subdivided into Alport's syndrome (with extrarenal involvement) and hereditary nephritis without deafness. Three modes of inheritance have been described: X-linked dominant, autosomal dominant, and autosomal recessive. We reviewed the mode of inheritance in 48 kindred with hereditary nephritis (41 with Alport's syndrome and 7 with hereditary nephritis without deafness). It was presumed X-linked dominant in 34 Alport's syndrome and 6 hereditary nephritis without deafness, autosomal dominant in five hereditary nephritis and one hereditary nephritis without deafness, and autosomal recessive in two Alport's syndrome. We studied the cumulative renal survival of 149 patients, 128 (76 males, 52 females) with Alport's syndrome and 21 (10 males, and 11 females) with hereditary nephritis without deafness. Major prognostic factors were the patient's sex (median renal survival in males and females being respectively 32 versus 61 years in Alport's syndrome and 34 versus 57 years in hereditary nephritis without deafness), and the mode of inheritance (median renal survival in males being 25 years in X-linked dominant Alport's syndrome versus 51 years in autosomal dominant Alport's syndrome). The presence of hearing loss in the kindred or in the patient himself did not appear as a significant prognostic factor. We conclude that Alport's syndrome and hereditary nephritis without deafness are predominantly X-linked dominant diseases with the same renal outcome, and that in Alport's syndrome the patient's sex and the mode of inheritance are two independent prognostic factors.