Alport syndrome, dominant type

A genetic disorder affecting the kidneys, ears, and eyes

Alport syndrome, dominant type
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Hematuria, proteinuria, hearing loss, eye abnormalities
Complications	Kidney failure, deafness
Onset	Childhood
Duration	Lifelong
Types	N/A
Causes	Genetic mutation in COL4A3, COL4A4, or COL4A5
Risks	Family history
Diagnosis	Genetic testing, kidney biopsy
Differential diagnosis	N/A
Prevention	N/A
Treatment	Supportive care, kidney transplant
Medication	N/A
Prognosis	N/A
Frequency	Rare
Deaths	N/A

Alport syndrome, dominant type is a genetic disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities. It is caused by mutations in the genes responsible for the production of type IV collagen, which is crucial for the structural integrity of the basement membranes in the kidneys, ears, and eyes.

Genetics

Alport syndrome is primarily caused by mutations in the COL4A3, COL4A4, or COL4A5 genes. The dominant type of Alport syndrome is usually associated with mutations in the COL4A3 or COL4A4 genes, which are located on chromosome 2. These mutations lead to defects in the alpha-3 or alpha-4 chains of type IV collagen, resulting in the characteristic symptoms of the disorder.

Clinical Features

The clinical presentation of Alport syndrome, dominant type, includes:

• Renal manifestations: The most common initial symptom is hematuria, or blood in the urine, which can be microscopic or macroscopic. Over time, patients may develop proteinuria and progressive chronic kidney disease, eventually leading to end-stage renal disease (ESRD).

• Auditory manifestations: Sensorineural hearing loss is a common feature, typically presenting in late childhood or early adolescence. The hearing loss is usually bilateral and progressive.

• Ocular manifestations: Eye abnormalities may include anterior lenticonus, a conical protrusion of the lens, and retinal flecks. These changes can lead to visual impairment.

Diagnosis

Diagnosis of Alport syndrome is based on clinical findings, family history, and genetic testing. A kidney biopsy may reveal characteristic changes in the glomerular basement membrane, such as thinning, splitting, and lamellation. Genetic testing can confirm the diagnosis by identifying mutations in the COL4A3, COL4A4, or COL4A5 genes.

Management

There is no cure for Alport syndrome, but management focuses on slowing the progression of kidney disease and addressing hearing and vision problems. Treatment options include:

• Renal management: Use of angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) to reduce proteinuria and slow kidney damage.
• Hearing management: Hearing aids or cochlear implants may be necessary for those with significant hearing loss.
• Vision management: Regular ophthalmologic evaluations and corrective lenses for visual impairments.
• Kidney transplantation: In cases of ESRD, kidney transplantation is the treatment of choice.

Prognosis

The prognosis for individuals with Alport syndrome, dominant type, varies depending on the severity of the kidney disease and the presence of other complications. With appropriate management, many patients can maintain a good quality of life.

Also see

• Alport syndrome
• Genetic disorders
• Chronic kidney disease
• Hearing loss
• Ocular diseases