White matter disorders may either be acquired or inherited. In adults, the white matter disorder is usually not inherited, although familial factors may play a role. Unfortunately, in children most white matter disorders are inherited.
There are also white matter disorders, which are not inherited. Infections may cause white matter damage. Some infections are acquired through the mother before birth, but also postnatal infections may cause white matter damage. Another cause is an allergic reaction of the white matter on an infection. Sometimes the disease is known but not its cause. It is clear that the white matter damage in multiple sclerosis is caused by inflammation, but the cause of the inflammation is not known. The white matter edema is another acquired white matter problem and may be seen in hydrocephalus or around brain tumors. In case of acquired disease, there is usually no increased risk in the other children of the family, although in some disorders there is a familial occurrence (example: multiple sclerosis).
There are different modes of inheritance. In order to understand something of inheritance, one has to know something of genetics. All humans have about 30,000 genes. All genes are present in a double set. One set comes from the mother; one set comes from the father.
The hereditary or genetic white matter disorders are caused by a defect in a gene. This gene abnormality will lead to dysfunction or abnormal amounts of a protein. As a consequence, this protein can no longer execute its function properly. Proteins can have different functions. They can have a function as an enzyme in a biochemical pathway. They can form a building block of the myelin sheath. Proteins can regulate other processes. If an enzyme will lose its function, a biochemical pathway will be disrupted. This may lead to an abnormal biochemical composition of myelin and eventually loss of myelin. If a myelin protein, a building block of myelin, will be formed in insufficient amounts or with an abnormal structure, the process of myelin formation will be hampered.
Autosomal recessive inheritance
The most frequent mode of inheritance is autosomal recessive. In order to understand what "autosomal recessive" means, one has to know that all humans have a few genes, on average 10, which contain a defect. This defect is not important, because one normal gene is enough to guarantee normal function. If both the father and the mother carry a defect in the same gene, there is a chance of 25% for each child they have that the child receives both defective genes and this child will have a disease. Carriership runs in families. The family does not know this because carriers are healthy. Only if one person has children with another carrier of the same disease, there is a chance that the disease comes to expression. The risk of recurrence in new children is for these parents 25% in each child.
Autosomal dominant inheritance
Another mode of inheritance is "autosomal dominant". This means that one gene with a defect is enough to cause a disease. In that case, either the father or the mother has the disease. There is a chance of 50% for each child to have the disease. It is also possible that the child has a new mutation. New defects in genes may arise and in case of autosomal dominant disease, this new defect will lead to a disease. In that case, there is no increased risk for following children. It is also possible that the father or the mother carries a new mutation in their germ cells. Then there is a risk of recurrence at following pregnancies, but not as high as 50%.
A third mode of inheritance is maternal. This mode of inheritance is seen in "mitochondrial disorders". Mitochondria are the structures that produce the energy in all cells of the body. They have a small piece of DNA in them with a small set of genes. The sperm cell has no mitochondria, but the ovum has mitochondria. This means that children have received all mitochondria from their mother. Defects in mitochondrial genes usually come from the mother and the mother gives the defect to all her children. Whether her children have symptoms depends on how high the percentage of abnormal mitochondria as opposed to the percentage of normal mitochondria. Sometimes, a child has a new mitochondrial gene defect, which is not found in the mother.