Alport Syndrome



  • A group of genetic diseases with defects in one of several subunits of type IV collagen that cause progressive hematuric nephritis and sensorineural deafness
  • Genetically heterogeneous defined as three types:
    • X-linked trait (XLAS): 80%
    • Autosomal recessive (ARAS): 15%
    • Autosomal dominant (ADAS): 5%


  • Varies according to genetics. Gene frequency is 1:5,000.
    • Gender
    • XLAS is more severe in males than females.
    • ARAS is equally severe in males and females.
  • Age
    • Hematuria: 1st year of life (XLAS)
    • Hearing loss and ocular abnormalities: late childhood or early adolescence
    • End-stage kidney disease (ESKD) by age 40 years in 90% of XLAS


  • In the United States, 3% of children and 0.2% of adults with ESKD:
    • 0.02% of the population
  • In Europe: 2.3% of patients with ESKD

Etiology and Pathophysiology

  • Mutations arrest the normal development of collagen in glomerular basement membrane (GBM) in cochlea and lens capsule:
    • Glomerular membranes thicken unevenly, split, and ultimately deteriorate.
    • This leads to mild proteinuria and sclerosis, with progression from concomitant interstitial nephritis and renal fibrosis.
  • X-linked dominant inheritance (XLAS)
    • Mutations in the COL4A5 gene encoding the α-5(IV) collagen chain on chromosome Xq26-48
  • Autosomal recessive inheritance (ARAS)
    • Mutations in the COL4A3 or COL4A4 gene encoding the 3(IV) or 4(IV) chain, respectively, on chromosome 2q35-37

See “Description.”

Risk Factors

  • For renal deterioration:
    • Clinical manifestations
      • Hypertension
      • Presence of nephrotic syndrome
  • Family history
    • Juvenile type: stereotypical course ESKD <20 years
    • “Nonprogressive” or adult type: variable course ESKD: age 40 years
  • Gender
    • XLAS is more severe; male > female; 90% males versus 15% females go to ESKD
    • ARAS: male = female
  • Type of inheritance
    • XLAS males and ARAS have a more severe disease than ADAS.
  • Type of mutations in type IV collagen genes

General Prevention

  • Genetic counseling
    • Genotype if possible (1)[C]
  • Renal follow-up
    • BP control
    • Monitoring of microalbuminuria by age 1 year (1)[C]
  • Hearing follow-up

Commonly Associated Conditions

  • Hearing defects
    • Sensorineural deafness
      • Frequent but not universal
      • Cochlear lesion
  • Ocular manifestations
    • Anterior lenticonus
      • 25% of patients
      • Pathognomonic feature
    • Dot-and-fleck retinopathy
    • Posterior polymorphous corneal dystrophy
  • Leiomyomatosis: 2–5% of families

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