X-linked Alport syndrome-diffuse leiomyomatosis

X-linked Alport syndrome-diffuse leiomyomatosis (also known as Alport syndrome with diffuse leiomyomatosis, or ATS-DL) is a rare genetic condition caused by large deletions involving the COL4A5 and COL4A6 genes on the X chromosome. These genes encode type IV collagen chains that are essential structural components of basement membranes in multiple organs. The condition combines the features of Alport syndrome — progressive kidney disease (glomerulonephritis leading to renal failure), sensorineural hearing loss, and ocular abnormalities — with diffuse leiomyomatosis, which is the widespread growth of benign smooth muscle tumors (leiomyomas) in the esophagus, tracheobronchial tree, and female genital tract. Affected males typically present in childhood or adolescence with dysphagia (difficulty swallowing), respiratory symptoms such as cough or dyspnea, and progressive renal impairment with hematuria and proteinuria. Esophageal leiomyomas are a hallmark feature and can cause significant swallowing difficulties. Females who carry the deletion may also develop leiomyomas, particularly of the genital tract (vulvar and uterine leiomyomas), and may have variable degrees of renal involvement and hearing loss. Ocular findings can include anterior lenticonus and retinal flecks. There is no cure for this condition. Management is multidisciplinary and supportive. Renal disease is managed with angiotensin-converting enzyme (ACE) inhibitors to slow progression, with kidney transplantation required for end-stage renal disease. Hearing aids are used for sensorineural hearing loss. Surgical intervention may be necessary for symptomatic leiomyomas, particularly esophageal tumors causing significant dysphagia. Genetic counseling is important for affected families given the X-linked inheritance pattern.

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