Genetic counseling

If the responsible mutation in an affected subject has been identified, regardless of whether or not it is in mtDNA or nuclear DNA, the successive family screening can be carried out with a simple blood test. This is important above all for mutations in mtDNA that are frequently associated with a wide variety of symptoms within the same family.
Along with those affected with serious symptoms there are often maternal relatives that have low or very low percentages of mutations and show only minor symptoms. Other family member may be completely asymptomatic. It is difficult to formulate a prognosis for these individuals because of the variable distribution of mutation in different tissues, the possible increase of mutations with time and the influence of non-mitochondral factors (i.e. environmental or due to the nuclear genetic background).

Genetic counseling for mitochondrial disease is particularly difficult and must be carried out in specialized institutions. However there are some guidelines that can be provided:

1. Males carrying mtDNA mutations cannot transmit disease to their offspring.

2. Likewise, except in extremely rare cases, women with PEO or Kearns- Sayre Syndrome with a documented deletion in mitochondrial DNA, cannot transmit disease to their children.

3. In families with a documented point mutation in mitochondrial DNA, all the women on the maternal side are at risk of having an affected child.

4. In families carrying pathogenic mutations of a nuclear gene, risk of recurrence follows Mendel’s laws, and varies in a predictable way according to whether it is dominant, recessive, or X-linked.

Pre-natal diagnosis is certain and safe only in the case of mutation in nuclear DNA. For mtDNA point mutations, it is not easy to formulate a prognosis since the percentage of mutated DNA present in the amniocytes or coryonic villi may not correspond to those present in critical fetal tissues such as muscle, heart and brain. Besides, such percentage can change either during the intrauterine development or after birth. Likewise, pre-natal diagnosis based only on biochemical evaluation of the respiratory chain is risky and can be performed only in particular cases and in specialized institutions.