The Meckel-Gruber syndrome (MKS) is a hereditary disease. It is characterized by severe congenital disabilities. Affected newborns usually die within the first two weeks after birth.
What is Meckel-Gruber Syndrome?
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The Meckel-Gruber syndrome is an inherited disorder characterized by kidney cysts, developmental disorders, and central nervous system disorders. The disease is also under the name Meckel syndrome known.
In Germany, 0.7 to 7.5 newborns per 100,000 births are statistically affected by the disease. The disease is much more common in Finland. One in 9000 newborns is affected here. If there is no termination of pregnancy, the children often die in the perinatal period, i.e. before the seventh day of life.
causes
The disease is inherited through an autosomal recessive genetic defect. In an autosomal recessive mode of inheritance, the genetic defect is on one of 22 so-called autosome pairs. Autosomes are chromosomes that, unlike gonosomes, have no influence on gender. The Meckel-Gruber syndrome is passed on regardless of gender. Recessive means that the disease only breaks out when two diseased genes, one from the father and one from the mother, are passed on to the child.
In order for a child to develop the Meckel-Gruber syndrome, both the father and mother of the child must be carriers of the disease. The parents show no symptoms as they each carry only one diseased gene. The second diseased gene is missing for the onset of the disease. The parents are also referred to as conductors, i.e. carriers of the defective gene. If both parents are conductors, the probability of developing Meckel-Gruber syndrome is statistically 25 percent.
If the parents are related, the probability increases. The gene that causes the disease has so far only been partially found. It appears that changes in three different gene locations are responsible for the disease. They are on chromosomes 17, 11 and 8.
Symptoms, ailments & signs
Cystic kidneys are characteristic of the Meckel-Gruber syndrome. Numerous fluid-filled vesicles form in the kidneys, so that the kidneys' filter function is severely restricted. The formation of kidney cysts is obligatory, that is, if there are no kidney cysts, it cannot be a question of Meckel-Gruber syndrome. Liver cysts can also occur. These sometimes lead to liver fibrosis. The children also suffer from encephalocele.
The brain is incorrectly designed and the skull is often not properly closed, so that parts of the brain bulge out of the skull. Other brain malformations were observed. A cleft lip and palate, a malformation of the mouth area, can also occur in the Meckel-Gruber syndrome. Often the newborns also suffer from microphthalmia. With microphthalmia, the eyes are unusually small or possibly only rudimentary.
Another symptom of the Meckel-Gruber syndrome is the so-called polydactyly, the multiple fingers. So there are more than ten fingers or ten toes. A double thumb on both sides is particularly common, so that the sick have twelve fingers instead of ten fingers.
A situs inversus is also a phenomenon of the hereditary disease. All organs are mirror-inverted on the other side of the body. For example, the heart is on the left and the liver on the right. Further symptoms of the Meckel-Gruber syndrome are malformations of the bile ducts and underdeveloped lungs.
Diagnosis & course of disease
The cyst kidney is an important clue in diagnosing Meckel-Gruber syndrome. The minimal diagnostic criteria for foot-and-mouth disease are cystic changes in the kidney, fibrotic changes in the liver, and encephalocele or other malformations of the central nervous system. The prenatal diagnosis of the disease is carried out using ultrasound.
A diseased fetus has a cystically altered interior of the skull, and sometimes other skull defects as well. The kidneys are also enlarged. These indications of the Meckel-Gruber syndrome can already be found at the end of the first trimester of pregnancy. As the pregnancy continues, other abnormalities may be detected by sonography.
An amniotic fluid test reveals an increased alpha-fetoprotein level. This is caused by the skull and CNS abnormalities and is a sure sign of severe skull deformity.
Complications
Unfortunately, due to the Meckel-Gruber syndrome, in most cases the patient dies a few weeks after birth. For this reason, the relatives and parents of the child in particular are affected by severe physical complaints or depression and therefore also need psychological treatment. Those affected themselves suffer from severe disabilities due to the Meckel-Gruber syndrome and cannot survive for this reason.
Above all, this leads to malformations of the kidneys and liver of the patient, leading to insufficiency and thus death. The patients also suffer from a so-called cleft palate and thus from restrictions on the intake of food. The life expectancy of patients is honestly restricted and reduced by the Meckel-Gruber syndrome.
Unfortunately, it is not possible to treat Meckel-Gruber syndrome or to resolve the symptoms. The children die very early after birth. Unfortunately, further measures to support life are not possible, so that there are no further complications. As a rule, the parents need psychological treatment after the child dies.
When should you go to the doctor?
People who suffer from the Meckel-Gruber syndrome already show severe health impairments at birth. Malformations and malfunctions can often be detected during the birth process. Many of the affected patients are born with a cleft lip and palate and should receive medical attention as soon as possible. In the case of an inpatient birth, the nurses and doctors present take over the first care of the newborn. Often times, immediate surgery is ordered to ensure the child's survival. Midwives and obstetricians take on these tasks in the case of a home birth or delivery in a birthing center. It is your responsibility to organize a transport of the child to the nearest hospital.
The parents therefore do not have to be active in these forms of birth. In the event of a spontaneous birth without the presence of medically trained nursing staff, an ambulance service should be alerted immediately. If the head is warped or deformed, the skull is open or the limbs are irregular, a doctor is urgently needed. The syndrome is characterized by the presence of more than ten fingers or toes. If breathing is impaired, additional first aid measures are required until the emergency doctor arrives so that the infant does not die within the first minutes of its life. Survival can only be ensured through mouth-to-mouth resuscitation.
Therapy & Treatment
The Meckel-Gruber syndrome cannot be treated. If a diagnosis is made before birth, termination of the pregnancy is often considered. Due to the severe malformations of the skull and organs, the mortality rate in the Meckel-Gruber syndrome is 100 percent, which means that all affected newborns are not viable in the long term. Most children die within the first seven days; no child usually lives more than two weeks.
Outlook & forecast
The prognosis for the Meckel-Gruber syndrome is extremely unfavorable. The syndrome is based on a genetic defect. This cannot be cured with the current medical possibilities. The child is born with severe disabilities and has little chance of survival. Due to legal requirements, doctors and researchers are not allowed to change human genetics in any way. As a result, doctors can only focus on using treatment options that provide relief from the various symptoms.
However, since multiple severe health restrictions have to be documented for this disease, the current treatment options are not sufficient to stabilize the person affected. Within a few days or weeks after delivery, all previously known cases of Meckel-Gruber syndrome lead to a premature death of the patient. Regardless of how early a diagnosis is made and how quickly extensive medical measures are taken, the average life expectancy of the person affected is between one and two weeks after the birth.
The physical malformations affect several areas of the skeletal system and organs. The newborn's body is too weak to survive the numerous operations necessary to stabilize the organism. Therefore, despite all efforts, organ failure and thus premature death will inevitably occur.
prevention
In principle, the Meckel-Gruber syndrome cannot be prevented. An early diagnosis does not prevent the disease, but only enables an earlier termination of pregnancy. Researchers have identified three genetic locations where the changes could be that are responsible for the serious hereditary disease. These locations are known as FMD loci:
- MKS1 is on chromosome 17
- MKS2 on chromosome 11
- MKS3 on the eighth chromosome.
Changes in the FMD3 gene have been detected in people from Pakistan. Changes in the FMD1 gene also occurred in Finland and Europe. A change in the FMD1 gene has so far been identified as a definitive cause of the disease. There is a genetic diagnosis that checks the presence of this defective gene. The prerequisite for this diagnosis to be carried out is that a reliable diagnosis of the Meckel-Gruber syndrome has already been made.
If the Meckel-Gruber syndrome can also be detected with genetic diagnostics in this sick child, genetic diagnostics can be carried out prenatal in further pregnancies. In this way, parents can be told with certainty whether their unborn child is the carrier of the genetic defect. It is also possible to test the parents if they suspect FMD. A blood test is carried out to determine whether you are the carrier of the genetic defect and whether there is a risk of passing the disease on to future offspring.
Aftercare
As a rule, the Meckel-Gruber syndrome also significantly reduces the life expectancy of children, so that they die only a few weeks after birth. Follow-up care focuses on the bereaved.
Sometimes professional psychological support can help deal with the loss of the child and the grief. Together with those affected, this develops therapeutic measures to absorb the severe psychological stress. If the parents who have already been affected wish to have children again, we recommend that they consult the treating gynecologist in order to determine the likelihood of another sick child in advance.
You can do that yourself
The Meckel-Gruber syndrome is a serious illness which in the vast majority of cases leads to the death of the child. Because of this negative prognosis, the most important self-help measure is to seek therapeutic support. The gynecologist can refer the parents to a suitable specialist, with whose help the typical fears and worries can be discussed and dealt with. Attending a self-help group is also recommended. Talking to other affected relatives makes it easier to deal with the disease and its mostly negative outcome.
Together with the responsible gynecologist, it must also be decided whether the child should be carried to term or aborted. Usually the parents decide to have an abortion because the chances of recovery are very slim, but in some cases a normal birth is also possible and sensible. As an alternative, there is a palliative delivery.
Regardless of what the parents choose, psychological support and the help of friends and relatives is needed. If the woman later wishes to become pregnant again, a comprehensive examination must be carried out to determine the chances of having a healthy child.
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