Miller-Dieker syndrome is a rare congenital developmental disorder of the brain and causes serious damage to the formation of brain structure. Miller-Dieker syndrome is caused by a genetic defect. The disease is not treatable and requires lifelong and loving care.
What is Miller-Dieker syndrome?
Miller-Dieker syndrome is a malformation of the brain, also known as lissencephaly. The term comes from the Greek for “smooth brain,” (lissos = smooth and encephalon = brain). The structure of a normal brain has numerous furrows (sulci) and convolutions (gyri), which begin to form around the 22nd week of pregnancy. In Miller-Dieker syndrome, this development is disturbed and the brain remains largely smooth. The disorder can occur in varying degrees, from decreased number to complete absence of brain convolutions. Miller-Dieker syndrome often also lacks the bar (corpus callosum), a structure that connects the two hemispheres of the brain and ensures their coordination. The maldevelopment of the brain leads to numerous severe disabilities of the newborn and causes a low life expectancy. Miller-Dieker syndrome is very rare, with an incidence of 1 in 50,000.
Causes
The cause of Miller-Dieker syndrome lies in the genetic makeup and is a mutation of chromosome 17, which is responsible for the formation of the cerebral cortex. However, it is also possible that the disorder is triggered by exposure to harmful substances during the second trimester of pregnancy. The changes in the genetic material may vary in severity. Sometimes the arms of the chromosome are too small, sometimes they are completely absent. Chromosome 17 normally ensures the migration of nerve cells from the inner cavities (ventricles) of the brain to the outside of the cortex. In Miller-Dieker syndrome, this migration is disturbed (migration disorder) and the nerve cells do not reach the cerebral cortex. As a result, the many necessary connections among the neurons do not occur, the furrows and convolutions do not form, and the smooth surface of the brain typical of Miller-Dieker syndrome develops.
Symptoms, complaints, and signs
The hallmark of this rare congenital disorder is that the brain does not develop normally. Typically, the furrows and folds of the cerebral cortex, which are present in a healthy brain, are almost completely absent. The surface is almost smooth. In some cases, a few rough furrows exist in a few areas. Already at birth, the infants are conspicuous by low Apgar scores; respiratory disorders may also occur. There is a marked mental retardation. The baby’s skull does not have a normal shape. While the back of the head is usually quite strongly formed, the head as a whole is too small and very narrow, which is called microcephaly. The temporal bones often show small depressions, the forehead is relatively high and may show increased wrinkling. The nose also shows abnormalities. It is only short, has a broad nasal root and the nostrils are directed forward instead of downward. The ears sit lower and deviate from the norm in shape and furrowing. The distance between nose and lips is excessive. The lower jaw is small and shifted backward, resulting in a receding chin. Affected children may suffer from seizures, as well as muscles that are too slack or too tense. Abnormalities of the genitals, malformations of internal organs, difficulty in feeding, and speech disorders also occur.
Diagnosis and course
The typical symptoms of Müller-Dieker syndrome are low birth weight and a small head caused by microencephaly (small brain). During birth, breathing difficulties may occur and Apgar scores, a scoring system that assesses the infant’s condition immediately after birth, are very low. Infants with Miller-Dieker syndrome have abnormalities of the face, such as a high forehead, a broad nose with upturned nostrils, low-set ears, a receding chin and a narrow upper lip. In Müller-Dieker syndrome, there are also malformations of organs, such as the heart, stomach, reproductive organs or urinary tract.The extremities often have more fingers or toes than normal (polydactyly) or individual limbs are fused together (syndactyly). In addition, seizures and movement disorders occur in Miller-Dieker syndrome. The diagnosis is usually made on the basis of the symptoms. Sonography (ultrasound examination) through the still open fontanelle and magnetic resonance imaging (produces cross-sectional images) reveal the maldevelopment of the brain. Typical changes can be seen in the EEG (measurement of brain waves). Finally, a genetic test can provide final certainty for the diagnosis of Müller-Dieker syndrome.
Complications
Miller-Dieker syndrome causes very severe and serious limitations in the patient’s life and daily routine. As a rule, those affected are dependent on lifelong care due to the syndrome and are unable to cope with everyday life on their own in the process. The malformations of the brain primarily lead to various mental and motor disorders and limitations. As a rule, these cannot be treated or therapized, since these malformations are irreversible. The patient’s skull is small and there are significant disturbances in the patient’s development. Likewise, a heart defect may occur, causing the affected person to die of cardiac death. Life expectancy is reduced by Miller-Dieker syndrome. In some cases, the malformations of the brain also lead to movement disorders or to convulsions. It is not uncommon for patients to suffer from spasticity and various facial abnormalities. Especially in children, Miller-Dieker syndrome can lead to bullying or teasing. There is no causal treatment for Miller-Dieker syndrome. Affected individuals are dependent on a lifetime of therapy and care. Special complications usually do not occur. Life expectancy itself is reduced to approximately ten years due to the syndrome.
When should you see a doctor?
Since Miller-Dieker syndrome is a congenital disease, it should always be examined and treated by a doctor. There is no self-healing in this case, so the complaints and symptoms can only be alleviated by the intervention of a medical professional. A doctor must usually be consulted for Miller-Dieker syndrome if the affected person suffers from respiratory and developmental problems. Most patients also show deficits in various school areas and can participate in everyday life only to a very limited extent. Likewise, Miller-Dieker syndrome can cause the head to be deformed, so that these complaints should also be examined by a doctor. In most cases, the syndrome itself is diagnosed by a doctor before or shortly after birth. Furthermore, a doctor should be visited if the patient suffers from convulsions or speech disorders. Not infrequently, the syndrome also leads to psychological complaints, which can occur not only in the affected person, but also in the relatives or parents. In this case, a visit to a psychologist is recommended. The Miller-Dieker syndrome itself is thereby treated by various specialists.
Treatment and therapy
There is no curative therapy for Miller-Dieker syndrome because the brain damage is irreversible. Once the brain has undergone the defective development, it cannot be reversed. One can only treat concomitantly to attenuate the symptoms. Anticonvulsant drugs help against seizures and physiotherapy can reduce movement disorders. If organs are damaged, appropriate treatments are given. Overall, children with Müller-Dieker syndrome require comprehensive and lifelong care. Life expectancy depends on the severity of the disease, but most children die within the first six months, and a few lived up to ten years.
Outlook and prognosis
The prognosis for an infant with Miller-Dieker syndrome (MDS) is conceivably unfavorable. For this reason, the overwhelming proportion of women decide to terminate the pregnancy before birth. In German-speaking countries, according to statistical surveys, this is said to be over 95 percent of expectant mothers. Both life expectancy and quality of life suffer with Miller-Dieker syndrome (MDS). Most infants die around six months of age. Heart defects in particular lead to early infant death.They occur in a good two-thirds of all children with MDS. Outliers upwards are rare. The oldest child was probably ten years old. Since disabilities are present, life is dependent on intensive medical support from the very beginning. The therapy is only able to alleviate the symptoms. A cure, on the other hand, is out of the question. The situation is not only stressful for the child itself. The parents in particular often suffer from the deformity. Some need psychological care to cope. It is important to perceive the child in its short life as an enrichment. Only in this way can accompaniment in the face of Miller-Dieker syndrome (MDS) be successful.
Prevention
One cannot prevent Miller-Dieker syndrome because the disease is caused by a genetic defect. However, one can have prenatal (pre-natal) testing. If Müller-Dieker syndrome is present, it is possible to terminate the pregnancy.
Follow-up care
In most cases, affected individuals have very few, if any, aftercare measures available to them for brain disorders. Yet early diagnosis usually always has a very positive effect on the further course of this disease and can limit further complications or further worsening of symptoms. Since the treatment of Miller-Dieker syndrome is relatively complex and lengthy, follow-up care focuses on good management of the disease. Affected individuals should try to establish a basic positive attitude to increase their sense of well-being. In this regard, relaxation exercises and meditation can help calm and focus the mind. Since brain diseases can also lead to psychological upsets, depression or an altered personality, most patients also rely on the support and help of their own family and friends in everyday life. Sometimes, accompanying therapy with a psychologist can alleviate the stresses and restore mental balance. The further course of aftercare depends strongly on the exact manifestation of the disease, so that no general prediction can be made.
What you can do yourself
Patients affected by Miller-Dieker syndrome suffer from severe mental disabilities and usually also from severe physical defects or impairments. Most patients die in infancy before their tenth birthday. These patients are neither able to cope with a normal everyday life nor do they have the ability to help themselves. In most cases, parents are entrusted with the care and nurturing of their severely disabled children. This presents the parents with a very difficult situation for which they have often been unable to prepare, and which they often feel unable to cope with. This is all too understandable. However, parents or other family caregivers can get expert help and should not hesitate to do so. Initial information about these options is already available at the hospital, and the pediatrician can also advise parents. Children affected by Miller-Dieker syndrome often suffer from severe pain from birth as a result of their health problems. Many forms of respiratory distress, difficult breathing and very difficult food intake also usually occur. It is therefore particularly important for patients to receive responsible and loving care and attention, as well as expert treatment. In most cases, palliative care is used, which can also be provided at home.
