Polymicrogyria

What is polymicrogyria?

Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) in the surface of the brain.

Polymicrogyria can affect part of the brain or the whole brain. When the condition affects one side of the brain, researchers describe it as unilateral. When it affects both sides of the brain, it is described as bilateral. The signs and symptoms associated with polymicrogyria depend on how much of the brain, and which particular brain regions, are affected.

Researchers have identified multiple forms of polymicrogyria. The mildest form is known as unilateral focal polymicrogyria. This form of the condition affects a relatively small area on one side of the brain. It may cause minor neurological problems, such as mild seizures that can be easily controlled with medication. Some people with unilateral focal polymicrogyria do not have any problems associated with the condition.

Bilateral forms of polymicrogyria tend to cause more severe neurological problems. Signs and symptoms of these conditions can include recurrent seizures (epilepsy), delayed development, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disorder, bilateral generalized polymicrogyria, affects the entire brain. This condition causes severe intellectual disability, problems with movement, and seizures that are difficult or impossible to control with medication.

Polymicrogyria most often occurs as an isolated feature, although it can occur with other brain abnormalities. It is also a feature of several genetic syndromes characterized by intellectual disability and multiple birth defects. These include 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger syndrome.

How common is polymicrogyria?

The prevalence of isolated polymicrogyria is unknown. Researchers believe that it may be relatively common overall, although the individual forms of the disorder (such as bilateral generalized polymicrogyria) are probably rare.

What genes are related to polymicrogyria?

In most people with polymicrogyria, the cause of the condition is unknown. However, researchers have identified several environmental and genetic factors that can be responsible for the disorder. Environmental causes of polymicrogyria include certain infections during pregnancy and a lack of oxygen to the fetus (intrauterine ischemia).

Researchers are investigating the genetic causes of polymicrogyria. The condition can result from deletions or rearrangements of genetic material from several different chromosomes. Additionally, mutations in one gene, GPR56, have been found to cause a severe form of the condition called bilateral frontoparietal polymicrogyria (BFPP). The GPR56 gene appears to be critical for the normal development of the outer layer of the brain. Researchers believe that many other genes are probably involved in the different forms of polymicrogyria.

Read more about the GPR56 gene.

How do people inherit polymicrogyria?

Isolated polymicrogyria can have different inheritance patterns. Several forms of the condition, including bilateral frontoparietal polymicrogyria (which is associated with mutations in the GPR56 gene), have an autosomal recessive pattern of inheritance. In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Polymicrogyria can also have an autosomal dominant inheritance pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Other forms of polymicrogyria appear to have an X-linked pattern of inheritance. Genes associated with X-linked conditions are located on the X chromosome, which is one of the two sex chromosomes. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Some people with polymicrogyria have relatives with the disorder, while other affected individuals have no family history of the condition. When an individual is the only affected person in his or her family, it can be difficult to determine the cause and possible inheritance pattern of the disorder.

Where can I find information about treatment for polymicrogyria?

These resources address the management of polymicrogyria and may include treatment providers.

• Gene Review: Polymicrogyria

You might also find information on treatment of polymicrogyria in Educational resources and Patient support.

Where can I find additional information about polymicrogyria?

You may find the following resources about polymicrogyria helpful. These materials are written for the general public.

• MedlinePlus - Health information
• Health Topic: Head and Brain Malformations
• Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases
• Educational resources - Information pages (2 links)
• Patient support - For patients and families (3 links)

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

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog (4 links)

What other names do people use for polymicrogyria?

• PMG

See How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about polymicrogyria?

• See How can I find a genetics professional in my area? in the Handbook.
• Ask the Genetic and Rare Diseases Information Center.
• Submit your question to Ask the Geneticist.

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What are the different ways in which a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

What glossary definitions help with understanding polymicrogyria?

autosomal ; autosomal dominant ; autosomal recessive ; bilateral ; cell ; cerebral cortex ; chromosome ; congenital ; deletion ; dysplasia ; family history ; fetus ; gene ; infection ; inheritance ; inheritance pattern ; ischemia ; mutation ; neurological ; oxygen ; pattern of inheritance ; prevalence ; rearrangement ; recessive ; seizure ; sex chromosomes ; sign ; symptom ; syndrome ; trait ; unilateral

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References

These sources were used to develop the Genetics Home Reference condition summary on polymicrogyria.

• Chang BS, Piao X, Giannini C, Cascino GD, Scheffer I, Woods CG, Topcu M, Tezcan K, Bodell A, Leventer RJ, Barkovich AJ, Grant PE, Walsh CA. Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation. Neurology. 2004 May 25;62(10):1722-8. Review. PubMed citation
• Dobyns WB, Mirzaa G, Christian SL, Petras K, Roseberry J, Clark GD, Curry CJ, McDonald-McGinn D, Medne L, Zackai E, Parsons J, Zand DJ, Hisama FM, Walsh CA, Leventer RJ, Martin CL, Gajecka M, Shaffer LG. Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2. Am J Med Genet A. 2008 Jul 1;146A(13):1637-54. PubMed citation
• Gene Review: Polymicrogyria
• Guerreiro MM, Andermann E, Guerrini R, Dobyns WB, Kuzniecky R, Silver K, Van Bogaert P, Gillain C, David P, Ambrosetto G, Rosati A, Bartolomei F, Parmeggiani A, Paetau R, Salonen O, Ignatius J, Borgatti R, Zucca C, Bastos AC, Palmini A, Fernandes W, Montenegro MA, Cendes F, Andermann F. Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment. Ann Neurol. 2000 Jul;48(1):39-48. PubMed citation
• Guerrini R, Barkovich AJ, Sztriha L, Dobyns WB. Bilateral frontal polymicrogyria: a newly recognized brain malformation syndrome. Neurology. 2000 Feb 22;54(4):909-13. PubMed citation
• Jansen A, Andermann E. Genetics of the polymicrogyria syndromes. J Med Genet. 2005 May;42(5):369-78. Review. PubMed citation
• Ohtsuka Y, Tanaka A, Kobayashi K, Ohta H, Abiru K, Nakano K, Oka E. Childhood-onset epilepsy associated with polymicrogyria. Brain Dev. 2002 Dec;24(8):758-65. PubMed citation
• Parrini E, Ferrari AR, Dorn T, Walsh CA, Guerrini R. Bilateral frontoparietal polymicrogyria, Lennox-Gastaut syndrome, and GPR56 gene mutations. Epilepsia. 2008 Nov 4; [Epub ahead of print]. PubMed citation
• Piao X, Chang BS, Bodell A, Woods K, Benzeev B, Topcu M, Guerrini R, Goldberg-Stern H, Sztriha L, Dobyns WB, Barkovich AJ, Walsh CA. Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann Neurol. 2005 Nov;58(5):680-7. PubMed citation
• Robin NH, Taylor CJ, McDonald-McGinn DM, Zackai EH, Bingham P, Collins KJ, Earl D, Gill D, Granata T, Guerrini R, Katz N, Kimonis V, Lin JP, Lynch DR, Mohammed SN, Massey RF, McDonald M, Rogers RC, Splitt M, Stevens CA, Tischkowitz MD, Stoodley N, Leventer RJ, Pilz DT, Dobyns WB. Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation. Am J Med Genet A. 2006 Nov 15;140(22):2416-25. PubMed citation