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Disease Profile

Miller-Dieker syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q04.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Miller-Dieker lissencephaly syndrome; MDLS

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

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]

Symptoms

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]

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.

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
Shortened nose
Decreased length of 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

Learn more

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.

      References

      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; https://ghr.nlm.nih.gov/condition/miller-dieker-syndrome.
      3. Pilz D. Miller-Dieker syndrome. Orphanet. 2005; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=531.
      4. Miller-Dieker Syndrome. Cortical Foundation. 2012; https://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; https://www.ncbi.nlm.nih.gov/books/NBK5189/.

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