XL Alport syndrome is characterised by haematuria which is present in nearly all affected males and females. In males, the haematuria is accompanied by proteinuria and progressive kidney failure. Ninety % of affected males have kidney failure requiring renal replacement therapy (dialysis or kidney transplantation) by the age of 40. However the average age at kidney failure is usually in the twenties. The hearing loss is first noted in boys in early childhood and progressively worsens until middle age when it plateaus. This mainly affects high-pitched sounds and is helped with the early use of hearing aids. Lenticonus is the conical protrusion of the anterior part of the lens which appears on ophthalmoscopy as an ‘oil droplet’ that moves with movement of the eye. Patients complain of difficulty with focusing. Lenticonus can be corrected with lens replacement, and does not recur. The fleck retinopathy is much more common than lenticonus and may be central or peripheral. It does not affect vision and patients are unaware of it. The flecks surround but do not encroach upon the macula and may be seen with ophthalmoscopy or non-mydriatic retinal photography. The peripheral retinopathy is more common but may only be evident on non-routine peripheral retinal views. The retinopathy does not require treatment.
Females with XL Alport syndrome typically develop proteinuria later than affected males. Hearing loss is common in middle age and again is helped with hearing aids. The association of the hearing loss with Alport syndrome may not be recognised. Lenticonus does not occur in affected women. The central fleck retinopathy may be present and the peripheral fleck retinopathy is very common.
The association of XL Alport syndrome with leiomyoma or smooth muscle tumours is rare and occurs with a large genetic deletion that affects both the COL4A5 and the adjacent COL4A6 gene. These tumours affect the trachea, bronchi, oesophagus, and female genital tract and may recur after resection. They are found in both men and women with this type of mutation.
COL4A5