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Epilepsy of infancy with migrating focal seizures
URL of this page: https://medlineplus.gov/genetics/condition/epilepsy-of-infancy-with-migrating-focal-seizures/

Epilepsy of infancy with migrating focal seizures

Description

Epilepsy of infancy with migrating focal seizures (EIMFS) is a form of recurrent seizures (epilepsy) that begins early in life. Seizures typically start before the age of 6 months. Babies with this condition can reach early developmental milestones, such as the ability to follow movement with their eyes or control their head movement. However, as seizure activity develops, children with EIMFS typically stop developing new skills and may experience a gradual loss of existing skills (developmental regression).

Focal motor seizures are the most common type of seizure seen in children with EIMFS. Focal motor seizures start in one area of the brain and affect muscle (motor) activity on one side of the body. Affected individuals may have more than one focal seizure at a time, and seizure activity can spread (migrate) from one brain region to another during an episode.

Although the seizures that are associated with EIMFS may be relatively infrequent at first, the seizure frequency increases rapidly. Affected individuals often experience several seizures per day; in some cases, the seizures may seem almost continuous. Children with EIMFS may also have individual seizures that last for several minutes (status epilepticus). After a year or more of persistent seizures, the episodes may become less frequent.

In children with EIMFS, seizures can affect the growth of the brain, leading to a small head size (microcephaly). The problems with brain development can also cause significant developmental delays and intellectual disabilities. Many affected individuals do not learn to walk or talk. Additional signs and symptoms of EIMFS may include weak muscle tone (hypotonia), abnormal tensing of the muscles (spasticity), and abnormal involuntary muscle movements.

EIMFS is one of a group of severe epilepsies called developmental and epileptic encephalopathies (DEEs). These disorders are characterized by significant developmental delays and seizures that begin early in life and may be difficult to treat.

Though some people with EIMFS have had milder signs and symptoms, many affected individuals do not survive past early childhood because of the serious health problems that are associated with this condition.

Frequency

EIMFS is estimated to occur in approximately 1 in 900,000 children.

Causes

The cause of EIMFS is not always known. Variants (also called mutations) in one of several different genes cause EIMFS in approximately 70 percent of cases. Researchers are studying how the features of EIMFS and the responses to various treatments differ in affected individuals depending on the particular gene involved. 

Variants in the KCNT1 gene are the most common genetic cause of EIMFS. The KCNT1 gene provides instructions for making a protein that helps form potassium channels. Potassium channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. The potassium channels made with the KCNT1 protein are active in nerve cells (neurons) in the brain. This flow of ions is involved in generating currents that activate (excite) neurons and send signals in the brain.

The KCNT1 gene variants that cause EIMFS typically lead to the substitution of one protein building block (amino acid) for another in the KCNT1 protein. This altered protein disrupts the function of the potassium channel. In most cases, the KCNT1 variants are described as “gain-of-function variants” because they increase the flow of potassium ions through the channel. The increased flow of potassium ions likely leads to the excitation of neurons and the repeated seizures seen in people with EIMFS.  

Variants in genes that provide instructions for making proteins that form sodium channels have also been found to cause EIMFS. These sodium channels transport sodium ions into cells, which helps cells generate and transmit electrical signals. The SCN2A gene provides instructions for making a protein that helps form part of the sodium channel, and variants in this gene are the second most common genetic cause of EIMFS. 

Sodium channels that are made with the SCN2A protein are active in neurons. Variants in the SCN2A gene can alter the structure and function of this protein. Researchers are working to learn more about the complex ways in which SCN2A gene variants affect the activity of sodium channels in the brain and how this change in activity results in the repeated seizures seen in children with EIMFS. 

In some cases, EIMFS has been associated with a group of disorders called congenital disorders of glycosylation (CDGs). CDGs are genetic conditions that affect a process called glycosylation, in which proteins are modified by adding sugar molecules. Glycosylation is necessary for the normal function of many different proteins.

Learn more about the genes associated with Epilepsy of infancy with migrating focal seizures

Additional Information from NCBI Gene:

Inheritance

EIMFS can be caused by variants in one of several different genes. The pattern of inheritance depends on the particular gene involved.

In many cases, EIMFS results from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

In some cases, EIMFS can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In a few families with a variant in the KCNT1 gene, some people who inherit the altered gene have not developed the features of the condition (reduced penetrance) or the affected individuals have had different signs and symptoms (variable expressivity).

EIMFS can also be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

When EIMFS is caused by a gene on the X chromosome, it is inherited in an X-linked pattern. A condition is considered X-linked if the altered gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is typically sufficient to cause the condition. In females (who have two copies of the X chromosome), one altered copy of the gene may or may not cause the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Other Names for This Condition

  • DEE 14
  • Developmental and epileptic encephalopathy 14
  • Early infantile epileptic encephalopathy 14
  • EIEE14
  • EIMFS
  • Epilepsy with migrating focal seizure in infancy
  • Malignant migrating partial epilepsy of infancy
  • Malignant migrating partial seizures of infancy
  • MFSI
  • Migrating focal seizures of infancy
  • Migrating partial epilepsy of infancy
  • Migrating partial seizures of infancy
  • MMPEI
  • MMPSI
  • MPEI
  • MPSI

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Barcia G, Chemaly N, Kuchenbuch M, Eisermann M, Gobin-Limballe S, Ciorna V, Macaya A, Lambert L, Dubois F, Doummar D, Billette de Villemeur T, Villeneuve N, Barthez MA, Nava C, Boddaert N, Kaminska A, Bahi-Buisson N, Milh M, Auvin S, Bonnefont JP, Nabbout R. Epilepsy with migrating focal seizures: KCNT1 mutation hotspots and phenotype variability. Neurol Genet. 2019 Oct 25;5(6):e363. doi: 10.1212/NXG.0000000000000363. eCollection 2019 Dec. Citation on PubMed
  • Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J, Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012 Nov;44(11):1255-9. doi: 10.1038/ng.2441. Epub 2012 Oct 21. Citation on PubMed or Free article on PubMed Central
  • Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium; Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE. The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures. Ann Neurol. 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. Citation on PubMed
  • Coppola G. Malignant migrating partial seizures in infancy: an epilepsy syndrome of unknown etiology. Epilepsia. 2009 May;50 Suppl 5:49-51. doi: 10.1111/j.1528-1167.2009.02121.x. Citation on PubMed
  • Fang ZX, Xie LL, Yan LS, Lin H, Pan YN, Liu BK, Jiang Y, Cheng M, Li XJ, Jiang L. Clinical and genetic characteristics of epilepsy of infancy with migrating focal seizures in Chinese children. Epilepsy Res. 2021 Aug;174:106669. doi: 10.1016/j.eplepsyres.2021.106669. Epub 2021 May 12. Citation on PubMed
  • Gertler T, Bearden D, Bhattacharjee A, Carvill G. KCNT1-Related Epilepsy. 2018 Sep 20. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK525917/ Citation on PubMed
  • Howell KB, McMahon JM, Carvill GL, Tambunan D, Mackay MT, Rodriguez-Casero V, Webster R, Clark D, Freeman JL, Calvert S, Olson HE, Mandelstam S, Poduri A, Mefford HC, Harvey AS, Scheffer IE. SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures. Neurology. 2015 Sep 15;85(11):958-66. doi: 10.1212/WNL.0000000000001926. Epub 2015 Aug 19. Citation on PubMed
  • Ishii A, Shioda M, Okumura A, Kidokoro H, Sakauchi M, Shimada S, Shimizu T, Osawa M, Hirose S, Yamamoto T. A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy. Gene. 2013 Dec 1;531(2):467-71. doi: 10.1016/j.gene.2013.08.096. Epub 2013 Sep 10. Citation on PubMed
  • McTague A, Appleton R, Avula S, Cross JH, King MD, Jacques TS, Bhate S, Cronin A, Curran A, Desurkar A, Farrell MA, Hughes E, Jefferson R, Lascelles K, Livingston J, Meyer E, McLellan A, Poduri A, Scheffer IE, Spinty S, Kurian MA, Kneen R. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum. Brain. 2013 May;136(Pt 5):1578-91. doi: 10.1093/brain/awt073. Epub 2013 Apr 18. Citation on PubMed or Free article on PubMed Central
  • McTague A, Kurian MA. SLC12A5-Related Epilepsy of Infancy with Migrating Focal Seizures. 2019 Feb 14. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK537476/ Citation on PubMed
  • Yang H, Yang X, Cai F, Gan S, Yang S, Wu L. Analysis of clinical phenotypic and genotypic spectra in 36 children patients with Epilepsy of Infancy with Migrating Focal Seizures. Sci Rep. 2022 Jun 17;12(1):10187. doi: 10.1038/s41598-022-13974-9. Citation on PubMed
  • Zeng Q, Yang Y, Duan J, Niu X, Chen Y, Wang D, Zhang J, Chen J, Yang X, Li J, Yang Z, Jiang Y, Liao J, Zhang Y. SCN2A-Related Epilepsy: The Phenotypic Spectrum, Treatment and Prognosis. Front Mol Neurosci. 2022 Mar 30;15:809951. doi: 10.3389/fnmol.2022.809951. eCollection 2022. Citation on PubMed

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