Alport Syndrome with Diffuse Leiomyomatosis (DL-ATS) is a rare condition seen in a subset of patients with Alport Syndrome with proven COL4A5 gene mutations.  Alport syndrome is a basement membrane disease involving type IV collagen, and is defined by glomerular nephropathy with hematuria associated with sensorineural deafness.  The renal phenotype ultimately leads to end stage renal disease.  Diffuse leiomyomatosis is characterized by benign smooth muscle cell proliferation in the female genital tract, trachiobronchal tree, and the esophagus.

The prevalence of DL-ATS is estimated at about 1 per million.  This forms about 5% of all cases of X-linked Alport Syndrome.  In males, this condition is usually characterized by a very severe nephropathy, rapidly progressing to end stage renal failue early in life.  The management of the renal condition may require the use of both hemodialysis and peritoneal dialysis.  Kidney transplantation is usually successful.  However, about 10% of transplanted patients have been reported to go on to develop nephritis in the graft.  The leiomyomatosis can be managed using surgical and hormonal treatment.

Alport Syndrome with Diffuse Leiomyomatosis is caused by mutations in the COL4A5 gene, located on the X-chromosome.  However, only certain mutations in this gene give rise to this condition.  These mutations include those affecting the 5’end of the COL4A5 gene and the adjacent COL4A6 gene.  Simultaneous mutations in both these genes are necessary for the development of DL-ATS.  In most cases, this involves a deletion mutation encompassing the 5’ end of both these genes.  Interestingly, the extent of the deletion into COL4A6 is limited to the first two exons.  Deletions further extending into the COL4A6 gene into the third exon do not result in leiomyomatosis.   Proteins coded by both these genes are an integral part of the collagen chain that are required for the structural integrity of the basement membranes.