What are the types of progressive muscular dystrophy included? What are the causative genes? What is the probability of inheritance?
Progressive muscular dystrophy includes pseudohypertrophic Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD), which are the most common types of the group of muscular dystrophies. The causative gene is the gene encoding the anti-myotonic dystrophy protein (dystrophin), called the DMD gene, localized in the short arm of the X chromosome, region 2, band 1, subband 2 (Xp21.2).
DMD and BMD are determined by the mutation site and nature of the DMD gene. Mutations that produce premature termination signals produce unstable RNA, which is rapidly degraded and cannot synthesize truncated proteins, causing DMD with severe clinical manifestations; mutations in the DMD gene that maintain gene translation and reading produce qualitatively and quantitatively reduced proteins that can retain partial function, causing BMD with milder clinical manifestations.
DMD is an X-linked recessive disorder with an incidence of 1/3500 in live births of male infants. if the mother is a carrier of the DMD mutation, there is a 50% chance that the mutation will be passed to the boy and that he will develop the disease; there is a 50% chance that the mutation will be passed to the girl, but most will not develop the disease and will be carriers in the same way as the mother.
Is it possible to have children with progressive myotonic dystrophy? How can I tell if I will pass it on to my offspring?
DMD/BMD is an X-linked genetic disorder. Most patients have a family history of the disease, but there are patients without a family history.
For male patients with DMD, the majority of patients cannot marry because there is no effective treatment available; male patients with BMD can have children if they are able to marry and under the guidance of genetic counseling. Testing for mutations in the DMD gene is recommended. In the case of male patients, if a daughter is born, the mutated X chromosome must be passed to the daughter and the daughter is the carrier; if a boy is born, because the Y chromosome is passed, the boy does not carry the mutation and therefore does not suffer from the disease. However, the mutation carried should also be clarified so as to better guide the birth of children and avoid the birth of further affected children in the next generation.
Is it possible to inherit the disease from a family member with progressive muscular dystrophy who does not show symptoms?
DMD/BMD is an X-linked genetic disorder. Most patients have a family history of the disease, but there is no family history of the disease.
With DMD/BMD in the family, there is a strong relationship between the gender of the members of the family and whether they are likely to be carriers of the DMD gene mutation. In men, if they are adults without any clinical manifestations and have completely normal serum enzymatic tests, the likelihood of carrying the mutation is low. For women, even if there is no clinical manifestation, the possibility of being a carrier of the mutation cannot be completely excluded.
Currently, because of the maturity of genetic testing methods, it is advisable for members with a family history to undergo genetic analysis before deciding to have children.
Do patients need to be tested for relevant genes during prenatal genetic counseling? Is it possible for patients to have their fetus genetically tested without genetic testing?
When having prenatal genetic counseling, patients need to be tested for genetic mutations.
If the patient is deceased, it is also important for female family members to be tested for the mutation before they plan to have children to try to rule out the possibility of being a carrier. If a carrier of the mutation is detected, prenatal genetic diagnosis must be done during pregnancy.
In addition, the clinical characteristics of DMD are that de novo mutations are common, sporadic and without a family history, i.e., the mother’s family does not have a patient; it is also possible that the mother who has already given birth to a child does not have a mutation in her peripheral blood genetic test, in which case gonadal chimerism (i.e., the mother has eggs with a mutation in her ovaries) cannot be ruled out. When germline chimerism is considered, the chance of having another child with DMD is high. Therefore, prenatal diagnosis should be performed for any further pregnancies in mothers with disseminated cases.
What is the accuracy of prenatal diagnosis when amniocentesis and chorionic villus testing are performed? Does the presence of a positive test indicate that the causative gene has been inherited, and does the presence of a negative test indicate that no inheritance has occurred?
The accuracy of prenatal diagnosis, either chorionic villus or amniocentesis, is high, greater than 95%, for those who have a clear pathogenic mutation in their family (as no work can be 100%). If the results of prenatal genetic diagnosis indicate that the fetus is male and has the same mutation as the male in the family, the likelihood of the disease being present at birth is very high and the fetus is generally judged to be diseased. If a female fetus is born with the same mutation as the male in the family, she is a carrier, and because of the effect of random inactivation of the X chromosome in females, some carriers may have clinical manifestations, but they are generally less severe than males.
In pregnant women with a clear mutation in the family, if the mutation is not found in the family in prenatal diagnosis, there is a high probability that it is not inherited, but due to the complexity of the mutation, it cannot be said that it is 100% free of mutations.
What institution can do prenatal genetic screening for this disease in fetuses?
It is best to have prenatal genetic diagnosis at a hospital qualified to do prenatal diagnosis.