National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Miller-Dieker syndrome


Other Names:
Miller-Dieker lissencephaly syndrome; MDLS
Categories:
Miller-Dieker syndrome (MDS) is a genetic condition characterized by a specific brain malformation (lissencephaly); distinctive facial features; and severe neurologic abnormalities including intellectual disability and seizures. Very few affected children survive beyond childhood.[1][2] MDS is caused by a deletion (missing piece) of genetic material on the short arm of chromosome 17 (17p).[2] Most cases are not inherited and occur randomly. In some cases, it is caused by inheriting a chromosome rearrangement (balanced translocation) from an unaffected parent.[2] Treatment is based on the symptoms in each person and aims to prevent complications and control seizures.[3]
Last updated: 5/18/2016
Miller-Dieker syndrome (MDS) is primarily associated with a type of abnormal brain development called lissencephaly (causing various neurological problems) and distinctive facial features. Additional birth defects may also be present. Sign and symptoms may include:
  • severe mental and physical developmental delays (most children do not learn to sit or walk)
  • intellectual disability
  • feeding and swallowing difficulties
  • low muscle tone (hypotonia)
  • seizures (beginning before 6 months of age)
  • microcephaly (smaller than normal head size)
  • slow growth
Generally, the more severe the brain abnormality is, the more severe the symptoms are.

Distinctive facial features may include:
  • a prominent forehead
  • a sunken appearance of the middle part of the face (midface hypoplasia)
  • a small, upturned nose
  • low-set and abnormally shaped ears
  • a small jaw (micrognathia)
  • a thick upper lip

Additional abnormalities that have been reported in some affected people include heart or kidney defects; an opening in the abdominal wall (omphalocele); contractures; and/or clinodactyly (curved finger).

Most people with MDS do not survive beyond childhood.[4]

Last updated: 5/18/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 59 |
Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Motor delay 0001270
80%-99% of people have these symptoms
Abnormality of upper lip 0000177
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
EEG abnormality 0002353
Epicanthus
Prominent eye folds
Eye folds
[ more ] 		0000286
Frontal bossing 0002007
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
High forehead 0000348
Lissencephaly
Fewer or absent grooves in brain
0001339
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Seizure 0001250
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
30%-79% of people have these symptoms
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Polyhydramnios
High levels of amniotic fluid
0001561
5%-29% of people have these symptoms
Ataxia 0001251
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Nephropathy 0000112
Omphalocele 0001539
Sacral dimple
Spinal dimple
0000960
1%-4% of people have these symptoms
Abnormality of cardiovascular system morphology 0030680
Cavum septum pellucidum 0002389
Deep palmar crease
Deep palm line
0006191
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Joint contracture of the hand 0009473
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Midline brain calcifications 0007045
Single transverse palmar crease 0000954
Thick upper lip vermilion
Full upper lip
Increased volume of upper lip
Plump upper lip
Prominent upper lip
Thick upper lip
[ more ] 		0000215
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
Percent of people who have these symptoms is not available through HPO
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect
[ more ] 		0001627
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Agyria 0031882
Autosomal dominant inheritance 0000006
Bitemporal hollowing 0025386
Camptodactyly
Permanent flexion of the finger or toe
0012385
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Cleft palate
Cleft roof of mouth
0000175
Contiguous gene syndrome 0001466
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption
[ more ] 		0000684
Duodenal atresia
Absence or narrowing of first part of small bowel
0002247
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Gray matter heterotopia 0002282
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Infantile spasms 0012469
Inguinal hernia 0000023
Pachygyria
Fewer and broader ridges in brain
0001302
Pelvic kidney 0000125
Polydactyly
More than five fingers or toes on hands or feet
0010442
Progressive spastic paraplegia 0007020
Recurrent aspiration pneumonia 0002100
Thin upper lip vermilion
Thin upper lip
0000219
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Showing of 59 |
Last updated: 7/1/2020
Many children with Miller-Dieker syndrome (MDS) do not live past age 2, and only a few may reach age 10. According to GeneReviews, as of 2014, the oldest known individual with MDS died at age 17 years.[5] In general, life expectancy is related to the severity of the lissencephaly.[5] The most common cause of death is aspiration pneumonia, caused by poor control of the airways.[4]

The developmental outlook is poor for all children with MDS, but varies slightly based on the degree of the brain malformation.[5][4] The highest developmental level in affected children is the equivalent of about 3 to 5 months of age, even with good seizure control. Very rarely, a child may be able to sit without help. Children with poor seizure control may function only at or below the level of a newborn.[5]
Last updated: 5/18/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Miller-Dieker syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about Miller-Dieker syndrome.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Miller-Dieker syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Carlos A Bacino. Microdeletion syndromes (chromosomes 12 to 22). UpToDate. Waltham, MA: UpToDate; April, 2016;
  2. Miller-Dieker syndrome. Genetics Home Reference (GHR). 2009; http://ghr.nlm.nih.gov/condition/miller-dieker-syndrome.
  3. Pilz D. Miller-Dieker syndrome. Orphanet. 2005; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=531.
  4. Miller-Dieker Syndrome. Cortical Foundation. 2012; http://cortfoundation.org/cms/get-informed/associated-syndromes/miller-dieker-syndrome/.
  5. William B Dobyns, MD and Soma Das. LIS1-Associated Lissencephaly/Subcortical Band Heterotopia. GeneReviews. August 14, 2014; http://www.ncbi.nlm.nih.gov/books/NBK5189/.