Meckel-Gruber syndrome (FMD) is an inherited disorder. It is characterized by the most severe congenital disabilities. Affected newborns usually die within the first two weeks after birth.
What is Meckel-Gruber syndrome?
Meckel-Gruber syndrome is an inherited disorder characterized by kidney cysts, developmental abnormalities, and central nervous system disorders. The condition is also known as Meckel syndrome. In Germany, the disease statistically affects 0.7 to 7.5 newborns per 100,000 births. In Finland, the disease occurs much more frequently. Here, one in 9,000 newborns is affected. If no abortion takes place, infants often die during the perinatal period, before the seventh day of life.
Causes
The disease is inherited through an autosomal recessive genetic defect. In autosomal recessive inheritance, the gene defect is located on one of 22 so-called pairs of autosomes. Autosomes are chromosomes which, in contrast to gonosomes, have no influence on the sex. Meckel-Gruber syndrome is therefore inherited independently of sex. Recessive means that the disease only comes to an outbreak when two diseased genes, one from the father and one from the mother, are passed on to the child. Thus, for a child to develop Meckel-Gruber syndrome, both the child’s father and mother must be carriers of the disease. The parents show no symptoms because they each carry only one diseased gene. The second diseased gene is missing for the onset of the disease. The parents are also called conductors, i.e. carriers of the defective gene. If both parents are conductors, the probability of contracting Meckel-Gruber syndrome is statistically 25 percent. If the parents are related, the probability increases. The disease-causing gene has only been partially found so far. It appears that changes in three different gene loci are responsible for the disease. They are located on chromosomes 17, 11, and 8.
Symptoms, complaints, and signs
Cystic kidneys are characteristic of Meckel-Gruber syndrome. In this condition, numerous fluid-filled vesicles form in the kidney, so that the filtering function of the kidneys is severely impaired. The formation of kidney cysts is obligatory, i.e. if no kidney cysts occur, it cannot be Meckel-Gruber syndrome. Liver cysts may also occur. These sometimes lead to liver fibrosis. The children also suffer from an encephalocele. In this case, the brain is defectively laid out and the skull is often not properly closed, so that parts of the brain bulge out of the skull. Other brain malformations have been observed. Cleft lip and palate, a maldevelopment of the mouth, can also occur in Meckel-Gruber syndrome. Newborns often also suffer from microphthalmia. In microphthalmia, the eyes are abnormally small or may be rudimentary. Another symptom of Meckel-Gruber syndrome is polydactyly. This means that there are more than ten fingers or ten toes. A double thumb on both sides is particularly common, so that the affected person has twelve fingers instead of ten. Another phenomenon of the hereditary disease is situs inversus. In this case, all organs are located mirror-inverted on the other side of the body. For example, the heart is on the left and the liver on the right. Other symptoms of Meckel-Gruber syndrome include malformations of the bile ducts and underdeveloped lungs.
Diagnosis and course of the disease
Cystic kidney is an important clue in the diagnosis of Meckel-Gruber syndrome. The minimal diagnostic criteria for FMD are cystic changes in the kidney, fibrotic changes in the liver, and encephalocele or other malformations of the central nervous system. Prenatal diagnosis of the disease is performed by ultrasound. In a diseased fetus, a cystic altered cranial cavity is found, sometimes other cranial defects. In addition, the kidneys are enlarged. These indications of 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 sonographically. An amniocentesis reveals an elevated alpha-fetoprotein level.This is caused by the skull and CNS abnormalities and is a sure indication of severe skull deformity.
Complications
Unfortunately, in most cases, Meckel-Gruber syndrome causes the death of the patient a few weeks after birth. For this reason, especially the relatives and the parents of the child are affected by severe physical discomfort or by depression and therefore also need psychological treatment. The affected persons themselves suffer from very severe disabilities due to the Meckel-Gruber syndrome and cannot survive for this reason. In particular, malformations of the patient’s kidneys and liver occur, resulting in insufficiency and thus death. The patients also suffer from a so-called cleft palate and thus from restrictions in the intake of food. The life expectancy of the patients is honestly limited and reduced by the Meckel-Gruber syndrome. Unfortunately, it is not possible to treat Meckel-Gruber syndrome or to solve the symptoms. In this case, the children die very early after birth. Unfortunately, further measures to preserve life are not possible, so that there are no further complications. Usually, the parents need psychological treatment after the death of the child.
When should you go to the doctor?
People who have Meckel-Gruber syndrome show severe health impairments as soon as they are born. Malformations and dysfunctions 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 care as soon as possible. In the case of an inpatient birth, attending nurses and physicians provide initial care for the newborn. Often, immediate surgical interventions are ordered to ensure the survival of the baby. In a home birth or a birth in a birth center, midwives and obstetricians assume these responsibilities. It is their responsibility to arrange for transport of the baby to the nearest hospital. Therefore, the parents do not have to become active in these forms of birth. In the case of a spontaneous birth without the presence of medically trained nursing staff, an ambulance service should be alerted immediately. In case of warping or deformation of the head, an open skullcap or irregularities of the limbs, a doctor is urgently needed. Characteristic of the syndrome is the presence of more than ten fingers or toes. If respiratory activity is impaired, additional first aid measures are required until the emergency physician arrives to ensure that the infant does not die within the first few minutes of life. Only mouth-to-mouth resuscitation can ensure survival.
Treatment and therapy
Meckel-Gruber syndrome cannot be treated. If diagnosed before birth, termination of the pregnancy is often considered. Because of the severe cranial and organ malformations, the lethality rate for Meckel-Gruber syndrome is 100 percent, meaning that all affected newborns are not viable in the long term. Most infants die within the first seven days, and no infant usually lives past two weeks of age.
Outlook and prognosis
The prognosis of Meckel-Gruber syndrome is extremely unfavorable. The syndrome is based on a genetic defect. This cannot be cured with current medical options. The child is born with severe disabilities and has almost no chance of survival. Due to legal regulations, doctors and researchers are not allowed to alter human genetics in any way. Therefore, doctors can only focus on using treatment options that lead to relief of the various symptoms. However, since multiple severe health limitations need to be documented in this disease, current treatment options are not sufficient to stabilize the affected individual. Within a few days or weeks after delivery, all cases of Meckel-Gruber syndrome known to date result in 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 affected person lies in a time window between one and two weeks after birth.The physical malformations affect several areas of the skeletal system as well as the organs. The newborn’s body is too weakened to survive the numerous operations necessary to stabilize the organism. Therefore, despite all efforts, organ failure inevitably results in premature death.
Prevention
In principle, Meckel-Gruber syndrome cannot be prevented. Early diagnosis does not prevent the disease, but only allows earlier termination of pregnancy. Researchers have identified three gene loci where the changes responsible for the severe inherited disease may be located. These locations are called FMD gene loci:
- FMD1 is located on chromosome 17.
- FMD2 located on chromosome 11
- FMD3 on the eighth chromosome.
Alterations in the FMD3 gene have been detected in people from Pakistan. Changes in the FMD1 gene also occurred in Finnish and European. So far, a change in the FMD1 gene has been identified as definitely causing the disease. There is a genetic diagnostic that tests for the presence of this defective gene. A prerequisite for this diagnosis is that a definite diagnosis of Meckel-Gruber syndrome has already been made. If Meckel-Gruber syndrome can also be detected with genetic diagnostics in this affected child, genetic diagnostics can be performed prenatally in further pregnancies. In this way, the parents can be told with certainty whether their unborn child is a carrier of the genetic defect. It is also possible to test the parents if FMD is suspected. For this, a blood test will determine whether they are carriers of the genetic defect and whether there is a risk of passing the disease to future offspring.
Follow-up
As a rule, Meckel-Gruber syndrome also significantly reduces the life expectancy of children, causing them to die just a few weeks after birth. In this case, aftercare focuses on the bereaved families. Sometimes, professional psychological care can help to deal with the loss of the child and with the grief. This develops therapeutic measures together with those affected in order to alleviate the severe psychological stress. If the parents, who have already been affected once, harbor a further desire to have children, they are recommended to have a consultation with the gynecologist treating them in order to determine in advance the likelihood of having another child with the disease.
What you can do yourself
Meckel-Gruber syndrome represents a severe disease that 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 professional, with whose help the typical fears and worries can be discussed and worked through. Attending a self-help group is also recommended. Talking to other affected relatives makes it easier to deal with the disease and its usually negative outcome. Together with the gynecologist in charge, a decision must also be made as to whether the child should be carried to term or aborted. In most cases, the parents decide in favor of an abortion, since the chances of a cure are very slim, but in some cases a normal birth is also possible and makes sense. An alternative is a palliative delivery. Regardless of what the parents decide, psychological support and the help of friends and relatives are necessary. If the woman later wishes to become pregnant again, a comprehensive examination must take place to determine the chances of bringing a healthy child into the world.