Alport Syndrome - Case Report
PATHOLOGY CASE REPORT
XL dominant Alport Syndrome: a rare condition and a rare mode of genetic transmission
INTRODUCTION
Alport syndrome (AS) is a rare abnormality of glomerular basement membrane caused by mutations in several different genes, all of which encode particular forms of type IV collagen, a major component of basement membrane. It is characterized by chronic renal failure leading to end-stage renal disease (ESRD) and is often associated with sensorineural deafness (Kanski 2003). The inheritance is typically XL dominant (about 80-85%) although autosomal recessive and autosomal dominant cases have been reported (Ermisch, Gross et al. 2000). The typical ocular signs are anterior lenticonus and scattered, pale, yellow, punctate flecks in the peri-macular region, sparing the fovea with normal visual acuity (Kanski 2003).
The X-linked form of the disease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen (Hertz, Juncker et al. 2001) whereas the autosomal forms are due to mutations in the COL4A3 or COL4A4 genes (Gubler, Knebelmann et al. 1995). The ocular manifestations of autosomal recessive Alport syndrome are probably identical to those for the X-linked form; although the mutations in these diseases affect genes for different type IV collagen chains, these chains occur together in the basement membranes of the kidney, eye and ear, and abnormalities in any one may result in the same clinical phenotype (Colville, Savige et al. 1997).
With respect to the prognosis of AS patients, males usually develop end-stage renal disease if not treated, whereas female patients have more variable phenotypes ranging from asymptomatic hematuria to ESRD. The variable phenotypes in female patients may be attributable to different X-chromosome inactivation patterns (Nakanishi, Iijima et al. 1998). A 15 year longitudinal study of patients with AS had two cases progress to renal failure at 15 and 21 years respectively, while 26
XL dominant Alport Syndrome: a rare condition and a rare mode of genetic transmission
INTRODUCTION
Alport syndrome (AS) is a rare abnormality of glomerular basement membrane caused by mutations in several different genes, all of which encode particular forms of type IV collagen, a major component of basement membrane. It is characterized by chronic renal failure leading to end-stage renal disease (ESRD) and is often associated with sensorineural deafness (Kanski 2003). The inheritance is typically XL dominant (about 80-85%) although autosomal recessive and autosomal dominant cases have been reported (Ermisch, Gross et al. 2000). The typical ocular signs are anterior lenticonus and scattered, pale, yellow, punctate flecks in the peri-macular region, sparing the fovea with normal visual acuity (Kanski 2003).
The X-linked form of the disease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen (Hertz, Juncker et al. 2001) whereas the autosomal forms are due to mutations in the COL4A3 or COL4A4 genes (Gubler, Knebelmann et al. 1995). The ocular manifestations of autosomal recessive Alport syndrome are probably identical to those for the X-linked form; although the mutations in these diseases affect genes for different type IV collagen chains, these chains occur together in the basement membranes of the kidney, eye and ear, and abnormalities in any one may result in the same clinical phenotype (Colville, Savige et al. 1997).
With respect to the prognosis of AS patients, males usually develop end-stage renal disease if not treated, whereas female patients have more variable phenotypes ranging from asymptomatic hematuria to ESRD. The variable phenotypes in female patients may be attributable to different X-chromosome inactivation patterns (Nakanishi, Iijima et al. 1998). A 15 year longitudinal study of patients with AS had two cases progress to renal failure at 15 and 21 years respectively, while 26