[MIM 150 700, 308 940, 301 050]

Prevalence 1/50.000. Progressive hereditary nephropathy due to a glomerulopathy and inconsistently associated with sensorineural deafness and ocular abnormalities. 

Mutation in the α3, α4, α5  or α6 chains of the IVA1 type collagen, an essential constituent of all basal membranes.

The genetic transmission is heterogenous:

-          dominant X-linked transmission of a mutation (microdeletion) of the COL4A5 gene (Xq22.3) in 85 % of cases  [MIM 301 050]; less severe in girls than in boys; in case of deletion involving the 5' terminal part of the COL4A5 and COL4A6 genes (contiguous gene syndrome), a diffuse leiomatosis is associated (see below)

-         autosomal recessive transmission of a mutation of the COL4A3 or COL4A4 gene (chromosome 2): severe disease in both sexes

-         autosomal dominant transmission (5 %) of a mutation in the gene coding for the α6 chain of collagen 4 (chromosome 4)

Clinical presentation: 

-         microscopic hematuria in childhood; proteinuria appearing in adolescence followed by a nephrotic syndrome; early administration of an ACE inhibitor or a sartan delays the development in certain mutations.

-         nephrocalcinosis

-         end stage renal disease in adolescence or in young adults (30-50 years of age) depending on the mutation

-         deafness: especially among boys and in severe forms

-         sometimes: thrombocytopenia

-         associated in approximately 5 % of cases with a diffuse leiomatosis [MIM 308 940] especially at the level of the esophageal wall (dysphagia, segmental stenosis, retrosternal pain) and the tracheobronchial wall (dyspnea) but also of the rectum (constipation); in female subjects, involvement of the external genitalia is possible at the level of the labia majora or the clitoris.

There are ocular lesions in 1/3 of the cases: congenital cataract, anterior lenticonus, fragile cornea (non-traumatic recurrent erosions).

Anesthetic implications: 

renal failure and deafness; arterial hypertension: LVH, echocardiography; eye protection. In case of dysphagia or retrosternal pain, check for an esophageal problem: risk of 'full' esophagus ! In case of dyspnea, chest X-Ray. A case has been reported with complete AV block during lumbar epidural anesthesia for a kidney transplantation.

References:

-         Ferrari F, Nascimento P, Vianna PT. 
Complete atrioventricular block during renal transplantation in a patient with Alport’s syndrome. 
Sao Paulo Med J 2001; 119: 184-6.

-         Bassareo PP, Marras AR, Mercuro G. 
Ventricular septal defect in a child with Alport syndrome:  case report. 
BMC Cardiovasc Disord 2010; 10: 48.

-        Anker MC, Arnemann J, Neumann K, Ahrens P, Schmidt H, Köning R. 
Alport syndrome with diffuse leiomyomatosis. 
Am J Med Genet 2003 ; 119A : 381-5

Updated: December 2019