HEREDITARY NEPHRITIS (ALPORTS-SYNDROME) - CLINICAL PROFILE AND INHERITANCE IN 28 KINDREDS

Sixty-three patients, (52 males and 11 females) from 28 kindreds of he reditary nephritis (Alport's syndrome) were identified over a 14-year period from 1977 to 1991. Group I included 51 patients with (a) positi ve family history of haematuria with or without chronic renal failure, (b) characteristic GBM changes on electron-microscopy, (c) characteri stic ocular signs, and (d) high-frequency sensorineural deafness. Grou p 11 included 12 patients with a negative family history. All of them had evidence of renal disease with characteristic ocular signs and dea fness and four had characteristic GBM changes on electron-microscopy. The main clinical features were haematuria in 96.8%, deafness in 82.5% , and diminished visual acuity in 66.7% of affected subjects. Hyperten sion was present in 71.4% patients. Pure tone audiometry revealed high -frequency sensorineural deafness in 96.8%. Ocular examination showed bilateral anterior lenticonus in 37.8%, retinal flecks in 22.2%, catar act in 20%, and keratoconus in 6.7% patients. Proteinuria (>2.0 g/24 h ) was detected in 31.8%. Sixteen (57.1%) of the 28 index patients (all males) were diagnosed for the first time when they presented with end -stage renal disease. Serum creatinine in the overall group ranged fro m 0.9 to 18.7 mg/dl(7.81 +/- 5.37 mg/dl). Adequate renal tissue was ob tained by biopsy in 14 patients. Light-microscopy revealed focal segme ntal glomerulosclerosis in five, mesangial proliferation in four, chro nic interstitial nephritis in three, and mesangiocapillary and crescen tic glomerulonephritis in one each. Electron-microscopy showed charact eristic changes in the GBM in seven specimens. The absence of male-to- male transmission, evidence of female-to-male and male-to-female trans mission as well as brothers, uncle-nephew pairs and affected individua ls being on the maternal side of the propositus, and males being more severely affected than females all strongly suggest an X-linked, proba bly dominant mode of inheritance in group I patients. A mutation invol ving the AlPort gene is suggested in 19% of our patients (group II).