NeurometPlus

Incidence

About 80% of Alport syndrome is X-linked; about 15% is autosomal recessive, and about 5% is autosomal dominant. Mutations in genes encoding isoforms of type IV collagen which is a component of basement membrane. The X-linked form is caused by mutations in COL4A5 gene which maps to the long arm of chromosome X (Xq22). The autosomal recessive form is caused by mutations COL4A3 and COL4A4 genes.

Clinical Characteristics

A genetically heterogenous disorder characterized by kidney abnormalities with hematuria and proteinuria, sensorineural hearing loss, and eye abnormalities. Two main genetically distinct forms are recognized: An X-linked dominant form with additional features including mental retardation, dysmorphic facies with midfacial hypoplasia, elliptocytosis and smooth muscle tumors; and an autosomal recessive form. Alport syndrome has renal, cochlear, and ocular manifestations. Because Alport syndrome is predominantly an X-linked disorder, these manifestations are typically more severe in affected males. However, affected females with either XLAS or ARAS may have severe involvement as well. ADAS is typically a slowly progressive disorder; renal insufficiency and sensorineural hearing loss may not develop until relatively late in life. Children with Alport syndrome are most often diagnosed in the first few years of life. The most common sign that first appears is blood in the urine (hematuria). The following symptoms can also be present as the disease progresses: Deafness, most often to high pitched tones, protein in the urine (proteinuria), high blood pressure, cataracts and nystagmus. The cause of Alport syndrome is due to a defective gene that is responsible for making collagen, a major protein making up the connective tissue that holds things together in our bodies. The collagen makes up the filtering part of the kidneys, and so children with Alport syndrome have \"leaky\" kidneys which ultimately leads to kidney failure.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

Diagnosis of Alport syndrome begins with examination of a child\'s urine, looking for protein and blood. Special hearing tests will also be done to assess a child\'s ability to hear high-pitched tones. A kidney biopsy will be necessary to officially diagnose Alport syndrome.