Last updated:
5/27/2025
Years published: 2022, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, Bailey Perczak, NORD Editorial Intern from the University of Notre Dame and Eric H. Kossoff, MD, Professor of Neurology and Pediatrics, Johns Hopkins University School of Medicine, for the preparation of this report.
Summary
Epilepsy with myoclonic-atonic seizures (EMAtS) is a rare childhood epilepsy syndrome characterized by myoclonic-atonic seizures which are typically recognized as jerking muscle contractions followed by sudden muscle limpness. This disorder is characterized by the presence of myoclonic-atonic seizures but affected people may also have other seizure types as well.
Because of these characteristics, EMAtS is classified as aa generalized seizure disorder, and it is also considered to be part of the GEFS+ (genetic epilepsy with febrile seizures plus) spectrum.
In most people the cause is unknown but there are some gene variants that have been identified as causing the disease. Males are affected at a rate nearly three times higher than females. The disorder typically occurs between the ages of 7 months and 6 years. Many of these children have normal development until the time that their seizures begin.
Diagnosis can include clinical evaluation and EEG (electroencephalogram) readings to detect abnormal brain waves. Various medications and dietary changes can be prescribed to control seizure activity. Ketogenic diet therapy is the most helpful therapy in most children.
Between 60-80% of people with EMAtS achieve seizure remission, whether through medical treatment or dietary regimens, but those whose seizures persist may be at risk for more intractable (hard to control) seizures and intellectual disabilities.
Introduction
Epilepsy with myoclonic-atonic seizures, or Doose syndrome, as it was first named, was coined in 1970 by Dr. Hermann Doose.
Epilepsy with myoclonic-atonic seizures (EMAtS), is a rare epilepsy syndrome that begins in early childhood. Most children have their first seizure between ages 1 and 5, and around 25% have their first seizure before their first birthday.
Before seizures begin, most children with EMAtS develop typically. However, about 20% may show mild developmental delays, often in speech.
The first seizure is usually a generalized tonic-clonic seizure (historically called a “grand mal” seizure). During the entire seizure, the child is unconscious and unaware of what’s happening. It usually takes a few minutes for them to wake up fully afterward.
This seizure has two phases:
Other seizure types in EMAtS may include:
Children whose seizures start after 4 years of age are more likely to begin with absence seizures.
After the initial seizure, most children develop multiple seizure types. Seizure frequency may increase and at peak severity, families may report 10 to 50 seizures per day.
In addition to seizures, children with EMAtS may also have:
The exact cause of EMAtS is unknown. About 34-44% of patients have at least one family member with a history of epilepsy but the type of seizure disorder is not the same among family members. However, all the different types of seizures in the family are within the GEFS+ (genetic epilepsy with febrile seizures plus) spectrum. The GEFS+ spectrum includes febrile or afebrile (non-fever induced) seizures and are recurrent. These conditions must be seen in several family members in different generations to be classified as GEFS+. The most frequent seizure types in people with GEFS+ include myoclonic, atonic and absence seizures.
Gene changes (variants) have been identified in some people with EMAtS. In some people, these variants were inherited from a parent and in other people they occurred for the first time in the affected person (de novo). Around 14% of people are found to have monogenic (single gene) variants. These variants are not present in all the affected people and some people develop the disorder without any familial history or genetic findings.
Variants in the following genes have been found in people with myoclonic atonic epilepsy:
– SLC6A1 (More frequently reported and is associated with increased levels of
severe intellectual disability, speech disorders and movement impairments. This gene codes for a major GABA transporter found in the central nervous system. GABA is an amino acid that blocks or slows nerve signals in the brain and plays a role in reducing anxiety, fear and stress.
– SLC2A1 (Found in a variety of brain disorders and correlates with speech, movement and intellectual impairments, along with decreased head size. Is known to result in GLUT1 transporter deficiency which impairs the body’s ability to transport glucose to the brain through the blood-brain barrier.
– SCN1A
– SCN1B
– SCN2A
– GABRG2
– CHD2 (Correlated with high levels of intellectual disability and photosensitive (light-sensitive) seizures.)
– SYNGAP1
– NEXMIF
– AP2M1
– KIAA2022
Children diagnosed with variants in these genes often have a more severe form of EMAtS or may present with more developmental delays prior to the onset of the seizures.
When EMAtS is due to variants in the SLC2A1 or SLC6A1 genes, some researchers think that the seizures are not caused directly by these gene changes. Instead, the seizures are thought to be part of a bigger neurological issue related to these gene variants.
For example, SLC2A1 variants cause a condition known as GLUT1 deficiency, where the brain doesn’t get enough glucose (sugar) which it needs for energy. This happens because GLUT1 transporters aren’t working properly and this may lead to brain dysfunction, including seizures.
EMAtS is rare. It accounts for only 1–2% of epilepsy cases, affecting fewer than 1 in 100,000 children each year. When EMAtS starts before age 1, boys are affected more often than girls (about 3 boys for every 1 girl). After age 1, boys and girls are equally affected. About 94% of children with EMAtS have their first seizure before age 5.
About one-third of children with EMAtS have relatives with epilepsy, often with febrile (fever-related) seizures. A smaller number have a family history of myoclonic or atonic seizures specifically.
EMAtS is diagnosed by a combination of clinical symptoms and EEG findings. People with EMAtS may have a variety of seizure types but the presence of myoclonic-atonic seizures is absolutely indicative of EMAtS. Additional findings typically include:
Genetic testing identifying variants in the SLC2A1 gene can confirm the diagnosis in some children.
Since some of the gene variants associated with EMAtS are treatable with medication and diet, genetic sequencing for variants such as SLC2A1 may be beneficial for the best management. A deficiency in GLUT1 transporters caused by these variants can also be diagnosed through lumbar puncture (spinal tap) to detect abnormal glucose levels in the spinal fluid.
Treatment
Treatment varies greatly from child to child. About 68% of children eventually stop having seizures but others may continue to struggle and need ongoing support.
First, doctors usually try anti-seizure medications like:
Only about 1 in 4 children respond well to these medications. However, a newer medication called felbamate has shown good results in some children with EMAtS.
If medications don’t work well, the ketogenic diet is often recommended. This high-fat, low-carbohydrate diet forces the body to use fat for energy instead of sugar. This change can reduce seizures by more than 50% in 80–90% of affected people. It works especially well for children with GLUT1 deficiency and may also improve learning and behavior.
Some medications can make seizures worse in EMAtS. These include:
These should be used cautiously or avoided unless the doctor recommends them for a specific reason.
Other treatments may include steroids (e.g., prednisolone), which can be used short-term if a child is having many seizures daily but long-term use can have serious side effects.
Many children benefit from occupational therapy (OT) for everyday skills, physical therapy (PT) for movement and strength and to improve overall function, and speech therapy for improving communication skills.
The outlook for children with EMAtS varies. About 60% develop normally, 20% have mild learning delays and 20% have moderate to severe delays
The chance of a better outcome improves with early diagnosis and treatment, especially if generalized tonic-clonic seizures (whole-body shaking seizures) are limited and non-convulsive status epilepticus (a type of long-lasting seizure without visible convulsions) is avoided.
Some current clinical trials relating to epilepsy conditions can be found on the following website:
https://www.epilepsy.com/clinical_trials
Patient registries and other research information can be found at the following website:
https://www.epilepsy.com/research-funding/rare-epilepsy-network/registry
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
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Kelley SA, and Kossoff EH. Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress. Developmental Medicine and Child Neurology. 2020. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2010.03744.x.
Tang S, et al. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic aeizures. Epilepsia. 2020; 27 Mar.https://slc6a1connect.org/wp-content/uploads/2020/06/Phenotypic-and-genetic-spectrum-of-epilepsy-with-myoclonic-atonic-seizures.pdf.
Wei Z, et al. Treatment of myoclonic-atonic epilepsy caused by SLC2A1 de novo mutation with ketogenic diet. Medicine. 2019;98:18 (e15428). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504322/pdf/medi-98-e15428.pdf.
Nickels K, Thibert R, Rau S, et al. How do we diagnose and treat epilepsy with myoclonic-astatic seizures (Doose syndrome)? Results of the Pediatric Epilepsy Research Consortium Survey. Epilepsy Res. 2018;144:14-19. https://pubmed.ncbi.nlm.nih.gov/29729532/
Larsen J, et al. The role of slc2a1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of glut1 deficiency syndrome. Epilepsia. 2015; 56(12):e203–e208.https://onlinelibrary.wiley.com/doi/pdf/10.1111/epi.13222
Trivisano M, et al. CHD2 mutations are a rare cause of generalized epilepsy with myoclonic–atonic seizures. Epilepsy & Behavior. 2015; 7 Aug. https://pubmed.ncbi.nlm.nih.gov/26262932
Thomas RH, Zhang LM, Carvill GL, et al. CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures. Neurology. 2015; vol. 84,9: 951-8. https://pubmed.ncbi.nlm.nih.gov/25672921/
Carvill GL, McMahon JM, Schneider A, et al. Mutations in the gaba transporter slc6a1 cause epilepsy with myoclonic-atonic seizures. AJHG. 2015 96, 5, 7 May:808-815. https://www.sciencedirect.com/science/article/pii/S0002929715000695
Roth FC and Draguhn A. GABA metabolism and transport: effects on synaptic efficacy. Neural Plasticity. 2012. https://www.hindawi.com/journals/np/2012/805830
Tang S and Pal DK. Dissecting the genetic basis of myoclonic‐astatic epilepsy. Epilepsia. 2012; 53(8):1303–1313. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03581.x.
Trivisano M, et al. Myoclonic astatic epilepsy: an age-dependent epileptic syndrome with favorable seizure outcome but variable cognitive evolution. Epilepsy Research. 2011; Nov;97(1-2):133-41. https://pubmed.ncbi.nlm.nih.gov/21873030/
Mullen SA, Marini C, Suls A, et al. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Arch Neurol. 2011;68(9):1152–1155. https://pubmed.ncbi.nlm.nih.gov/21555602/
Kilaru S and Bergqvist AGC. Current treatment of myoclonic astatic epilepsy: clinical experience at the Children’s Hospital of Philadelphia. Epilepsia. 2007; 48(9):1703–1707 https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2007.01186.x.
Stephani U. The natural history of myoclonic astatic epilepsy (DOOSE syndrome) and Lennox‐Gastaut syndrome. Epilepsia. 2006; 47(Suppl. 2):53–55. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2006.00690.x
Gayatri NA, and Livingston JH. Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine and Child Neurology. 2006; 48: 394–398. https://onlinelibrary.wiley.com/doi/epdf/10.1017/S0012162206000843.
Nabbout R., et al. Absence of mutations in major Gefs+ genes in myoclonic astatic epilepsy. Epilepsy Research. 2003;56:127-133. https://www.sciencedirect.com/science/article/pii/S0920121103001530.
Dulac O. Epileptic encephalopathy. Epilepsia 2001;42 Suppl 3 23-6. doi:10.1046/j.1528-1157.2001.042suppl.3023.x/.
Kaminska A, et al. Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis Epilepsy.1999. https://pubmed.ncbi.nlm.nih.gov/10463847/
INTERNET
Epilepsy with myoclonic-atonic seizures. Orphanet. April 2021. https://www.orpha.net/en/disease/detail/1942 Accessed May 15, 2025.
Myoclonic Atonic Epilepsy. Online Mendelian Inheritance in Man (OMIM). 11/22/2021. https://omim.org/entry/616421?search=Myoclonic%20Atonic%20Epilepsy.&highlight=atonic%2Cepilepsy%2Cmyoclonic Accessed May 15, 2025.
Epilepsy with Myoclonic-Atonic Seizures. International League Against Epilepsy. June 30, 2024. https://www.epilepsydiagnosis.org/syndrome/epilepsy-myoclonic-atonic-overview.html. Accessed May 15, 2025.
Appleton R. Myoclonic Astatic Epilepsy (Doose Syndrome). Epilepsy Action. October 2023. https://www.epilepsy.org.uk/info/syndromes/myoclonic-astatic-epilepsy-doose-syndrome. Accessed May 15, 2025.
Hernandez A, and Wirrell E. Myoclonic Atonic Epilepsy (Doose syndrome). Epilepsy Foundation. Nov. 2019. https://www.epilepsy.com/learn/types-epilepsy-syndromes/myoclonic-atonic-epilepsy-doose-syndrome Accessed May 15, 2025.
Epilepsy with Myoclonic-Atonic Seizures. Genetic and Rare Diseases Information Center. Last updated: 7/25/2018. https://rarediseases.info.nih.gov/diseases/2169/epilepsy-with-myoclonic-atonic-seizures Accessed May 15, 2025.
What Is Doose Syndrome? Doose Syndrome Epilepsy Alliance. https://doosesyndrome.org/. Accessed May 15, 2025.
Facebook group: https://www.facebook.com/groups/DooseSyndrome Accessed May 15, 2025.
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