What Is Miller Dieker Syndrome?
Miller-Dieker syndrome (MDS) is a rare genetic condition characterized by an abnormal brain developmental condition known as lissencephaly, where a person has an abnormally smooth brain with the absence of sulci and gyri, which are the elevations and depression seen in a normal brain. The absence of sulci and gyri leads to severe intellectual disabilities, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. The symptoms of the disorder have been seen since childhood. Seizures usually begin before six months of age, and in some cases, the symptoms can be present at birth, which makes it difficult for a child to survive, leading to death in most cases.
Miller-Dieker Syndrome is also called:
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Classical lissencephaly syndrome.
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MDS.
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Miller-Dieker lissencephaly syndrome.
What Are the Symptoms of Miller Dieker Syndrome?
As Miller-Dieker syndrome leads to an anomaly of the brain, some common symptoms observed are as follows:
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Prominent forehead.
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The sunken appearance of mid-face.
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Abnormally shaped ears.
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Upturned nose.
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Thick lips.
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Retarded growth.
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Organ malformation.
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Airway obstructions and breathing difficulties.
How Is Miller Dieker Syndrome Caused?
Miller-Dieker syndrome is a rare genetic disorder; researchers have reported it to be caused due to deletion of genetic material at the end of the short arm of chromosome 17. PAFAH1B1 is the gene located on chromosome 17 which is considered responsible for the characteristic feature of lissencephaly in patients with Miller-Dieker syndrome, another gene on the same locus of chromosome 17 called the YWHAE gene is responsible for enhancing the severity of lissencephaly in affected patients. In addition, studies have reported the role of various other genes which present varied symptoms of the condition.
How Is Miller Dieker Syndrome Diagnosed?
As the disorder is congenital, most of the symptoms are present at birth as the characteristic facial features or appear during the early days after birth. These children find it difficult to achieve milestones and rarely complete two or three milestones, like sitting or rolling. Therefore a thorough clinical examination and identification of characteristic symptoms is the key to diagnosing this syndrome.
The diagnosis can be confirmed after carrying out the following specialized diagnostic tests:
X-Rays: Specialized imaging techniques are used to assess craniofacial abnormalities. These radiographs help determine defects like micrognathia, mandibular hypoplasia, bone-forming defects, etc.
Molecular Genetic Testing: This testing can be done only in specialized laboratories and helps detect a genetic mutation in the DHODH gene. This test is used as a confirmatory test for the Miller-Dieker syndrome.
Prenatal Ultrasound: This imaging technique detect abnormal brain development and other signs of the syndrome during pregnancy.
Genetic Amniocentesis: This is the amniotic fluid test that helps indicate the genetic disorder during intrauterine life.
Chorionic Villus Sampling: This is the method of examining the placental cells.
Which Other Disorders Have a Similar Presentation?
The symptoms of the Miller-Dieker syndrome are often confused with other disorders as they have a similar presentation. Below listed are some of such disorders:
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Nager syndrome (also known as preaxial acrofacial dysostosis).
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Treacher Collins syndrome (TCS).
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Postaxial acrofacial dysostosis.
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Acrofacial dysostosis syndrome of Rodriguez.
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Weyers acrofacial dysostosis.
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Miller syndrome.
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Pallister-Hall syndrome.
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Mandibulofacial dysostosis.
How to Treat Patients with Miller Dieker Syndrome?
No definitive treatment is known for children with Miller-Dieker syndrome; symptomatic treatment prolongs the patient's life span and prevents complications by providing symptomatic relief. Treating patients with millers requires a team of specialists who coordinate amongst themselves to solve and prevent bigger complications. The medical team includes pediatricians, oral surgeons, plastic surgeons, pediatric ear, nose, and throat specialists, ophthalmologists, otologists, audiologists, nephrologists, and other physicians who might be needed to plan treatment. Affected individuals should be referred to higher centers for coordinated craniofacial care.
Surgery: Surgical procedures might be required to avoid life-threatening complications like breathlessness, where a procedure called a planned tracheostomy is performed. Other surgeries that might be required include jaw surgery, insertion of the feeding tube, cleft lip, and cleft palate repair, and correction of the heart defect if any congenital defect is present.
The treatment should be initiated at the earliest to prevent developmental delays and physical abnormalities. Children with hearing defects should be provided with a hearing aid so that it does not affect their speech and learning.
Genetic Counseling: An individual with known family history or parents with one child affected must consider genetic counseling and psychological support to prevent further cases. As in cases with one child affected, there is a possibility of having a faulty gene in either of the two parents.
Therefore, it is important to love and raise a child though it is challenging; this phase can even make parents prone to anxiety and depression; therefore, as a parent, they must follow and involve in the following:
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Activities of the support groups.
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Spending self-time or participating in self-motivating activities.
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Gathering information and knowledge about the child's condition.
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Consulting the health care professional and psychologist at regular intervals.
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Consulting rehabilitation centers for children.
What Are the Complications of Miller Dieker Syndrome?
Miller-Dieker Syndrome is a genetic disorder with no cure; thus, fatality or a short life span is the biggest complication of this syndrome; the person who lived the longest with the Miller-Dieker syndrome was until the age of 30. Usually, any child with this syndrome cannot make it more than three years of age due to the systemic complications of the disease. The most common cause of death in these cases is respiratory obstruction, feeding problems, or seizures. Even if the person with this syndrome survives following are the common complications faced:
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Seizures.
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Feeding difficulties due to cleft palate.
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Multiple organ damage or malformation.
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Speech difficulties.
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Aspiration pneumonia.
Conclusion
Miller-Dieker Syndrome is a rare genetic disorder that affects one in 100,000 children; this disorder does not have any hereditary or familial inheritance pattern. This syndrome is present at birth, and infants with this syndrome present with characteristic facial features; common complications include seizures, respiratory obstruction, feeding problems, etc. The condition is diagnosed clinically and is fatal. Unfortunately, no definitive treatment is available; thus, these children are treated symptomatically.
