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Genetics Home Reference: your guide to understanding genetic conditions
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Miller-Dieker syndrome

Reviewed November 2009

What is Miller-Dieker syndrome?

Miller-Dieker syndrome is a condition characterized by a pattern of abnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. These brain malformations cause severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. Seizures usually begin before six months of age, and some occur from birth. Typically, the smoother the surface of the brain is, the more severe the associated symptoms are.

In addition to lissencephaly, people with Miller-Dieker syndrome tend to have distinctive facial features that include a prominent forehead; a sunken appearance in the middle of the face (midface hypoplasia); a small, upturned nose; low-set and abnormally shaped ears; a small jaw; and a thick upper lip. Some individuals with this condition also grow more slowly than other children. Rarely, affected individuals will have heart or kidney malformations or an opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel. People with Miller-Dieker syndrome may also have life-threatening breathing problems. Most individuals with this condition do not survive beyond childhood.

How common is Miller-Dieker syndrome?

Miller-Dieker syndrome appears to be a rare disorder, although its prevalence is unknown.

What are the genetic changes related to Miller-Dieker syndrome?

Miller-Dieker syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. The signs and symptoms of Miller-Dieker syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals.

Researchers are working to identify all of the genes that contribute to the features of Miller-Dieker syndrome. They have determined that the loss of a particular gene on chromosome 17, PAFAH1B1, is responsible for the syndrome's characteristic sign of lissencephaly. The loss of another gene, YWHAE, in the same region of chromosome 17 increases the severity of the lissencephaly in people with Miller-Dieker syndrome. Additional genes in the deleted region probably contribute to the varied features of Miller-Dieker syndrome.

Related Chromosome(s)

Changes involving this chromosome are associated with Miller-Dieker syndrome.

  • chromosome 17

Related Gene(s)

Changes in these genes are associated with Miller-Dieker syndrome.

  • PAFAH1B1
  • YWHAE

Can Miller-Dieker syndrome be inherited?

Most cases of Miller-Dieker syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.

When Miller-Dieker syndrome is inherited, its inheritance pattern is considered autosomal dominant because a deletion in one copy of chromosome 17 in each cell is sufficient to cause the condition. About 12 percent of people with Miller-Dieker syndrome inherit a chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Miller-Dieker syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 17, which results in the health problems characteristic of this disorder.

Where can I find information about diagnosis or management of Miller-Dieker syndrome?

These resources address the diagnosis or management of Miller-Dieker syndrome and may include treatment providers.

  • Gene Review: LIS1-Associated Lissencephaly/Subcortical Band Heterotopia (http://www.ncbi.nlm.nih.gov/books/NBK5189)
  • Genetic Testing Registry: Miller Dieker syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265219)

You might also find information on the diagnosis or management of Miller-Dieker syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/miller-dieker-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/miller-dieker-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Miller-Dieker syndrome?

You may find the following resources about Miller-Dieker syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Miller-Dieker syndrome?

  • classical lissencephaly syndrome
  • MDS
  • Miller-Dieker lissencephaly syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Miller-Dieker syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Miller-Dieker syndrome?

autosomal ; autosomal dominant ; cell ; cerebral cortex ; chromosome ; deletion ; developmental delay ; disability ; gene ; hypoplasia ; hypotonia ; inherit ; inheritance ; inheritance pattern ; inherited ; kidney ; muscle tone ; omphalocele ; prevalence ; rearrangement ; reproductive cells ; sign ; spasticity ; sperm ; syndrome ; translocation

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Allanson JE, Ledbetter DH, Dobyns WB. Classical lissencephaly syndromes: does the face reflect the brain? J Med Genet. 1998 Nov;35(11):920-3. (http://www.ncbi.nlm.nih.gov/pubmed/9832039?dopt=Abstract)
  • Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J, Gross A, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB, Ledbetter DH. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am J Hum Genet. 2003 Apr;72(4):918-30. Epub 2003 Mar 5. (http://www.ncbi.nlm.nih.gov/pubmed/12621583?dopt=Abstract)
  • Dobyns WB, Curry CJ, Hoyme HE, Turlington L, Ledbetter DH. Clinical and molecular diagnosis of Miller-Dieker syndrome. Am J Hum Genet. 1991 Mar;48(3):584-94. (http://www.ncbi.nlm.nih.gov/pubmed/1671808?dopt=Abstract)
  • Nagamani SC, Zhang F, Shchelochkov OA, Bi W, Ou Z, Scaglia F, Probst FJ, Shinawi M, Eng C, Hunter JV, Sparagana S, Lagoe E, Fong CT, Pearson M, Doco-Fenzy M, Landais E, Mozelle M, Chinault AC, Patel A, Bacino CA, Sahoo T, Kang SH, Cheung SW, Lupski JR, Stankiewicz P. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. J Med Genet. 2009 Dec;46(12):825-33. doi: 10.1136/jmg.2009.067637. Epub 2009 Jul 6. (http://www.ncbi.nlm.nih.gov/pubmed/19584063?dopt=Abstract)
  • Spalice A, Parisi P, Nicita F, Pizzardi G, Del Balzo F, Iannetti P. Neuronal migration disorders: clinical, neuroradiologic and genetics aspects. Acta Paediatr. 2009 Mar;98(3):421-33. doi: 10.1111/j.1651-2227.2008.01160.x. Epub 2008 Dec 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19120042?dopt=Abstract)
  • Sweeney KJ, Clark GD, Prokscha A, Dobyns WB, Eichele G. Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development. Mech Dev. 2000 Apr;92(2):263-71. (http://www.ncbi.nlm.nih.gov/pubmed/10727864?dopt=Abstract)
  • Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 2003 Jul;34(3):274-85. (http://www.ncbi.nlm.nih.gov/pubmed/12796778?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2009
Published: December 16, 2014