What Is Miller Dieker Syndrome?

  • Anna Bourouliti PhD Neuroscience, D.U.Th., Democritus University of Thrace, Greece
  • Reem Alamin Hassan Bachelor's degree, Biomedical Sciences, Queen Mary University of London, UK

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Miller-Dieker syndrome (MDS) is a neurological disorder that affects newborns and infants. It is caused by a genetic abnormality in one of the chromosomes of human DNA. While symptoms may vary, MDS generally leads to abnormal formation of brain structures, which also affects the facial features of patients with the disorder. Unfortunately, newborns with MDS have a short lifespan, which usually does not extend beyond childhood1. Consequently, there is an evident need for the development of proper diagnostic tools and effective treatment methods. The following paragraphs aim to aid understanding of what MDS is, how it is prenatally diagnosed, and the current approaches towards treatment of symptoms.

Genetic factors that cause MDS

MDS is caused by an abnormal deletion of part of chromosome 17 (17p13.3 deletion)1. Essentially, chromosomes are made of DNA. They are the “packaging” units of human DNA. Each human carries 46 chromosomes that come in pairs, so it is 23 pairs of chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes) that comprise the human genome. Each cell of the human body contains in its nucleus a copy of these chromosome pairs, and each time a cell divides, the chromosomes are copied and then distributed in each daughter cell. Mistakes may occur when copying or distributing genetic material. These mistakes lead to the so-called “numerical” or “structural” abnormalities, which can be the cause of various disorders. MDS falls into the latter category of structural abnormalities as it is missing a part of one of the chromosomes while the total number of them remains normal.

Such alterations in the number or structure of chromosomes may be de novo, meaning they happen at the stages of cell differentiation and division of the organism and are not inherited by parents, but they might sometimes also occur during the production of the reproductive cells (sperms and eggs), called gametes. This happens in the gametes of either males or females, which eventually means that the abnormality may be inherited from the embryo by one of its parents. The parents have normal body cells, but an error during the division of the gametes of either one of them has led to the deletion of genetic material. As a result, the abnormality that occurred during cell division in one of the parents will potentially only be evident in their offspring, who will inherit the genetic material of the affected gamete. As this material will come from only one of the two parents, it is only half of the total genes the offspring has. However, the normal half of the genome cannot always compensate for the missing part of the other half, especially in cases where the error has a large impact.2 In such cases, the inheritance of the abnormality is called “dominant” as it dominates over the normal genetic counterpart. MDS follows the dominant inheritance pattern, and because of the fact the abnormality is located on an autosome and not a sex chromosome, its inheritance pattern is called “autosomal dominant”.1

To sum up, an error in the genetic material that might occur during the production of reproductive cells in one of the parents can be the cause of MDS development in the newborn child.1

MDS symptoms

Symptoms associated with brain structures and the central nervous system

MDS is associated with the more general term of lissencephaly.1 Lissencephaly is a malformation of the brain regarding the folds and grooves that characterise the brain structure. The reduction or absence of these folds is the main feature of lissencephaly and results in a seemingly “smooth” brain. Lissencephaly is caused by abnormalities during brain development, which are associated with genetic factors.3 Unfortunately, most cases with MDS suffer from severe lissencephaly, and this is considered to affect their survival.4 Apart from MDS, other syndromes characterised by lissencephaly are X-linked lissencephaly with abnormal genitalia and Baraitser-Winter cerebrofrontofacial syndrome.3

Aside from lissencephaly, cases of MDS may also exhibit atrophy in the outer layer of the brain, namely the cerebral cortex. Sometimes, the underdevelopment of another region of the inner part of the brain called the corpus callosum, may be observed. Moreover, about 90% of children with MDS exhibit seizures by their first year of age4 of which are caused by abnormalities in brain activity. Occasionally, MDS also involves the development of ataxia. The term ataxia refers to difficulties in movement, namely difficulties in coordination and synchronisation of movements or movements that seemingly lack distance perception.1

Symptoms manifesting in facial characteristics

Children with MDS usually show facial traits that are characteristic of conditions associated with the syndrome. These may be abnormalities of the upper lip or the forehead, which is higher than normal in cases of MDS. Other symptoms manifest on the nose. The nose may be short in length either when measured as the distance from the base of the forehead to the upper lip or when measured from the bridge to the sticking-out nose tip. Another symptom regarding the nose may be the anteverted nares. In anteverted nares, the nose looks like an abnormally/overly upturned nose. Abnormalities in the eye are also a symptom of MDS. More specifically, a condition called epicanthus may be observed in children with MDS. Epicanthus refers to a fold of skin that connects the upper and the lower lid at the part of the eye that is near the base of the nose, and it is actually observed in a plethora of disorders, and not just MDS.1 Finally, abnormalities in ears and jaw have also been reported.4

Other symptoms

Underdevelopment may be a more general symptom in MDS cases as they sometimes show impaired growth in regards to the time that it normally takes for a baby to grow, either before or after childbirth. Growth delay may also be regarded as delays in the development of intellectual functions.4 In addition, in regards to obvious symptoms that manifest on the body, MDS children may develop clinodactyly a malformation of the fifth finger, which could be described as bending. Other symptoms observed in MDS include omphalocele, which concerns protruding of the newborn’s intestines out of the belly; sacral dimple, which is a condition of the skin and refers to an indentation at the lower part of the back where one end of the spine is located; nephropathies; cardiovascular abnormalities; and polyhydramnios, which is observed during pregnancy and refers to the presence of an excessive amount of amniotic fluid within the uterus. Despite the numerous symptoms associated with MDS, it should be noted that their occurrence may vary in each case.1


Unfortunately, the prognosis for MDS is poor. Consequently, there is an urgent need for early diagnosis, more specifically, prenatally, during the early stages of embryonic development. In the past years, the diagnosis of embryos with deletions in chromosome 17 was carried out using G-banding karyotyping.5 G-banding karyotyping involves dying chromosomes at specific sites and helps the identification of chromosomal numerical and structural abnormalities. Nowadays, more sensitive techniques are being used in order to detect even little changes in the embryo’s genetic material.6 These sensitive techniques are often utilised in case of suspicion about an MDS case. Suspicion may arise either due to the manifestation of the syndrome in another child within the family. Other signs may be the aforementioned symptom polyhydramnios or abnormalities observed early in brain development through ultrasound testing. If all the appropriate tests show indeed that the embryo is going to develop MDS, then the parents might opt to terminate the pregnancy.7

Treatment and management

MDS is considered a rare condition, and data from research about the disorder are lacking. Reported MDS cases are few so studies on treatment are also limited. As a result, not only is there no absolute cure, but there is also no medication that can relieve a broad range of symptoms. Usually, management of MDS involves attending to each separate symptom when and if it affects the patient. For example, pharmaceutical compounds used to treat epileptic seizures may also constitute treatment for seizures in MDS cases. Generally, the current management of MDS involves approaches that aim to prolong the life of patients and increase the quality of their lives. Hopefully, future advances in gene therapy methods will aid in treating chromosomal abnormalities of MDS and other syndromes of similar origin.4

Families of patients with MDS can ask for information and support in groups designated to help manage rare disorders. Patient organisations can help easily find relevant information and specialists on MDS, as well as get in touch with other people who share similar experiences and can offer their stories, views, and even emotional support. In each country, different organisations provide the appropriate help and proper guidelines for the management of MDS.1


Despite being a rare condition, Miller-Dieker syndrome (MDS) calls for more research in the field as its prognosis is unfortunately poor. Symptoms generally appear shortly after birth, while there are a few prenatal characteristics that may serve as signs of MDS. Since a high percentage of newborns with MDS do live beyond their first year after birth, it is of great importance that an early prenatal diagnosis is made. Sadly, we are yet far from treating MDS, even though there is an existing medication that can improve specific symptoms. Evidently, there is a need to increase awareness of MDS, intensify research, and make advances in tools and methods that will allow for better treatment and, hopefully, a much longer lifespan.4


  1. National Center for Advancing Translational Sciences. NIH. Genetic and Rare Diseases Information Center. Miller-Dieker syndrome. [Internet]. Last Updated: February 2023. https://rarediseases.info.nih.gov/diseases/3669/miller-dieker-syndrome Accessed Oct 2023.
  2. Genetic Alliance; The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2009 Jul 8. APPENDIX F, CHROMOSOMAL ABNORMALITIES. Available from: https://www.ncbi.nlm.nih.gov/books/NBK115545/. Accessed Oct 2023
  3. Di Donato N, Chiari S, Mirzaa GM, Aldinger K, Parrini E, Olds C, et al. Lissencephaly: Expanded imaging and clinical classification. American journal of medical genetics Part A. 2017;173(6):1473-88. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526446/ 
  4. Bahmad HF, Ramesar L, Nosti C, Anthonio G, Brathwaite C, Vincentelli C, et al. Histopathologic Findings Associated with Miller-Dieker Syndrome: An Autopsy Report. Diseases (Basel, Switzerland). 2022;10(4). https://pubmed.ncbi.nlm.nih.gov/36412589/ 
  5. Zhang YL, Jing XY, Zhen L, Pan M, Han J, Li DZ. Prenatal diagnosis of Miller-Dieker syndrome/PAFAH1B1-related lissencephaly: Ultrasonography and genetically investigative results. European journal of obstetrics, gynecology, and reproductive biology. 2022;274:28-32. https://pubmed.ncbi.nlm.nih.gov/35567955/ 
  6. Huang H, Chen J. Chromosome Bandings. Methods in molecular biology (Clifton, NJ). 2017;1541:59-66. https://pubmed.ncbi.nlm.nih.gov/27910014/ 
  7. Shi X, Huang W, Lu J, He W, Liu Q, Wu J. Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray. Annals of human genetics. 2021;85(2):92-6. https://pubmed.ncbi.nlm.nih.gov/33026665/ 

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Anna Bourouliti

PhD Neuroscience, D.U.Th., Democritus University of Thrace, Greece

Back when I was a curious little creature, I was fascinated by science and aspired to work in a laboratory. To satisfy my thirst for scientific knowledge, I pursued studies in Molecular Biology and Genetics, entered the field of Health Sciences, and eventually fulfilled my dream of conducting research. This journey began with my undergraduate studies and progressed to obtaining an MSc and later, a PhD degree in Neurosciences. I have now left hands-on experiments behind, and I currently work as a medical writer, monitoring advancements in health sciences from a close perspective.

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