COL4A1 / COL4A2 syndrome is a very rare genetic disorder.
Diseases that affect a small number of people are defined as rare and consequently generate specific problems related to their rarity. The limit established in Europe is one affected person out of 2.000.
Type IV alpha 1 and alpha 2 collagen (COL4A1 and COL4A2) is the main component of almost all basement membranes. For this reason, a mutation of the COL4A1 or COL4A2 gene causes a disorder that can affect any organ but typically the alteration in the gene is associated with the disease of the small cerebral vessels, a disorder transmitted as an autosomal dominant trait (it is sufficient that a single copy of the gene is altered for the disease to occur), with variable age of onset (from neonatal to adulthood) and incomplete penetrance. From a clinical point of view, the severity of the manifestations is very variable (from severe early onset to mild paucisymptomatic cases).
The main symptoms occur in the Central Nervous System (hemiplegia, epileptic seizures, intellectual disability of varying degrees, motor symptoms, headache) and derive from vascular alterations that lead to cerebral degeneration. At the neuroradiological level, various anomalies can be highlighted: leukoencephalopathy of varying severity, micro- and macro-bleeding in the subcortical area, lacunar infarcts, dilation of the perivascular spaces, aneurysms of the intracranial cerebral arteries and porencephalic cysts. There may occur also manifestations at the ocular level (tortuous retinal artery, anterior chamber anomalies, congenital cataract, glaucoma, microphthalmia, optic atrophy), muscle (muscle cramps and increase in muscle enzymes), renal (cyst, hematuria and glomerulopathy), hepatic (cyst), cardiovascular (heart rhythm abnormalities, mitral aortic valve prolapse), hematological (hemolytic anemia) and Raynaud’s phenomenon.
COL4A1 / COL4A2 syndrome is diagnosed following a genetic test that reveals the mutation in COL4A1 or COL4A2 genes. If one of the parents is also a carrier of the mutation, it is considered hereditary. If neither parent carries the mutation, it is considered de novo. In cases where the mutation is inherited, the carrier parent is often clinically healthy. This can occur if the carrier has mosaicism: some cells carry the mutation while others do not. The degree of mosaicism is highly variable – ranging from only a small percentage of cells with the mutation to nearly all cells carrying the mutation – and depends on the stage in development at which the mutation occurred. It is important to discuss these issues with a geneticist and understand the implications.
There is currently no cure.
Therapy is symptomatic and supportive, as well as rehabilitative.
More information on the COL4A1 / COL4A2 is available at: rarediseases.org