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Developmental and epileptic encephalopathy 94(DEE94)

MedGen UID:
815608
Concept ID:
C3809278
Disease or Syndrome
Synonyms: CHD2-Related Neurodevelopmental Disorders; DEE94; Epileptic encephalopathy, childhood-onset
 
Gene (location): CHD2 (15q26.1)
 
Monarch Initiative: MONDO:0014150
OMIM®: 615369

Disease characteristics

Excerpted from the GeneReview: CHD2-Related Neurodevelopmental Disorders
CHD2-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common. [from GeneReviews]
Authors:
Gemma L Carvill  |  Heather C Mefford   view full author information

Additional descriptions

From OMIM
Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by onset of multiple seizure types in the first few years of life and associated with poor prognosis. Affected individuals have cognitive regression and impaired intellectual development (summary by Carvill et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.  http://www.omim.org/entry/615369
From MedlinePlus Genetics
CHD2 myoclonic encephalopathy is a condition characterized by recurrent seizures (epilepsy), abnormal brain function (encephalopathy), and intellectual disability. Epilepsy begins in childhood, typically between ages 6 months and 4 years. Each individual may experience a variety of seizure types. The most common are myoclonic seizures, which involve involuntary muscle twitches. Other seizure types include sudden episodes of weak muscle tone (atonic seizures); partial or complete loss of consciousness (absence seizures); seizures brought on by high body temperature (febrile seizure); or tonic-clonic seizures, which involve loss of consciousness, muscle rigidity, and convulsions. Some people with CHD2 myoclonic encephalopathy have photosensitive epilepsy, in which seizures are triggered by flashing lights. Some people with CHD2 myoclonic encephalopathy experience a type of seizure called atonic-myoclonic-absence seizure, which begins with a drop of the head, followed by loss of consciousness, then rigid movements of the arms. Epilepsy can worsen, causing prolonged episodes of seizure activity that last several minutes, known as status epilepticus. The seizures associated with CHD2 myoclonic encephalopathy are called refractory because they usually do not respond to therapy with anti-epileptic medications.

Other signs and symptoms of CHD2 myoclonic encephalopathy include intellectual disability that ranges from mild to severe and delayed development of speech. Rarely, individuals can have a loss of acquired skills (developmental regression) following the onset of epilepsy. Some people with CHD2 myoclonic encephalopathy have autism spectrum disorders, which are conditions characterized by impaired communication and social interaction. In some instances, areas with a loss of brain tissue (atrophy) have been found with medical imaging.  https://medlineplus.gov/genetics/condition/chd2-myoclonic-encephalopathy

Clinical features

From HPO
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Status epilepticus without prominent motor symptoms
MedGen UID:
199677
Concept ID:
C0751523
Disease or Syndrome
There is inconclusive evidence to precisely define the duration of the seizure; however, based on current evidence an operational threshold of 10 minutes is appropriate as beyond this a seizure is likely to be more prolonged. The individual may or may not be aware or in coma.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Visually-induced seizure
MedGen UID:
1720648
Concept ID:
C2080645
Disease or Syndrome
Seizures evoked by visual stimuli. This includes clinical seizures induced by strobe lighting, television and other screens, flickering environmental lighting and self-induction by causing a strobe effect.
EEG with generalized spikes
MedGen UID:
777018
Concept ID:
C2206531
Finding
EEG with generalized sharp transient waves of a duration less than 80 msec.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Multifocal epileptiform discharges
MedGen UID:
866864
Concept ID:
C4021219
Finding
An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci).
Generalized myoclonic seizure
MedGen UID:
892704
Concept ID:
C4021759
Disease or Syndrome
A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
EEG with generalized polyspikes
MedGen UID:
868685
Concept ID:
C4023088
Finding
EEG with repetitive generalized sharp transient waves of a duration less than 80 msec.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.

Professional guidelines

PubMed

Thiel M, Bamborschke D, Janzarik WG, Assmann B, Zittel S, Patzer S, Auhuber A, Opp J, Matzker E, Bevot A, Seeger J, van Baalen A, Stüve B, Brockmann K, Cirak S, Koy A
J Neurol Neurosurg Psychiatry 2023 Oct;94(10):806-815. Epub 2023 May 24 doi: 10.1136/jnnp-2022-330261. PMID: 37225406
Sánchez Fernández I, Abend NS, Amengual-Gual M, Anderson A, Arya R, Barcia Aguilar C, Brenton JN, Carpenter JL, Chapman KE, Clark J, Farias-Moeller R, Gaillard WD, Gaínza-Lein M, Glauser T, Goldstein J, Goodkin HP, Guerriero RM, Lai YC, McDonough T, Mikati MA, Morgan LA, Novotny E Jr, Payne E, Peariso K, Piantino J, Ostendorf A, Sands TT, Sannagowdara K, Tasker RC, Tchapyjnikov D, Topjian AA, Vasquez A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; pSERG
Neurology 2020 Sep 1;95(9):e1222-e1235. Epub 2020 Jul 1 doi: 10.1212/WNL.0000000000010174. PMID: 32611646Free PMC Article
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article

Recent clinical studies

Etiology

Masri AT, Oweis L, Ali M, Hamamy H
Clin Neurol Neurosurg 2023 Jul;230:107799. Epub 2023 May 22 doi: 10.1016/j.clineuro.2023.107799. PMID: 37236004
Cioclu MC, Mosca I, Ambrosino P, Puzo D, Bayat A, Wortmann SB, Koch J, Strehlow V, Shirai K, Matsumoto N, Sanders SJ, Michaud V, Legendre M, Riva A, Striano P, Muhle H, Pendziwiat M, Lesca G, Mangano GD, Nardello R; KCNT2-study group, Lemke JR, Møller RS, Soldovieri MV, Rubboli G, Taglialatela M
Ann Neurol 2023 Aug;94(2):332-349. Epub 2023 May 22 doi: 10.1002/ana.26662. PMID: 37062836
Haneder C, Stark B, Peherstorfer A, Gröppel G
Seizure 2022 Mar;96:95-97. Epub 2022 Feb 12 doi: 10.1016/j.seizure.2022.02.008. PMID: 35183031
Pisani F, Spagnoli C
Handb Clin Neurol 2019;162:401-414. doi: 10.1016/B978-0-444-64029-1.00019-9. PMID: 31324322
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article

Diagnosis

Daniels C, Greene C, Smith L, Pestana-Knight E, Demarest S, Zhang B, Benke TA, Poduri A, Olson HE; CDKL5 Study Group
Dev Med Child Neurol 2024 Apr;66(4):456-468. Epub 2023 Sep 28 doi: 10.1111/dmcn.15747. PMID: 37771170Free PMC Article
Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Masri AT, Oweis L, Ali M, Hamamy H
Clin Neurol Neurosurg 2023 Jul;230:107799. Epub 2023 May 22 doi: 10.1016/j.clineuro.2023.107799. PMID: 37236004
El-Dib M, Abend NS, Austin T, Boylan G, Chock V, Cilio MR, Greisen G, Hellström-Westas L, Lemmers P, Pellicer A, Pressler RM, Sansevere A, Tsuchida T, Vanhatalo S, Wusthoff CJ; Newborn Brain Society Guidelines and Publications Committee
Pediatr Res 2023 Jul;94(1):64-73. Epub 2022 Dec 7 doi: 10.1038/s41390-022-02393-1. PMID: 36476747
Haneder C, Stark B, Peherstorfer A, Gröppel G
Seizure 2022 Mar;96:95-97. Epub 2022 Feb 12 doi: 10.1016/j.seizure.2022.02.008. PMID: 35183031

Therapy

Stefanos-Yakoub I, Wingeier K, Held U, Latal B, Wirrell E, Smith ML, Ramantani G
Epilepsia 2024 Feb;65(2):251-265. Epub 2023 Dec 9 doi: 10.1111/epi.17834. PMID: 38031640
Juliá-Palacios N, Molina-Anguita C, Sigatulina Bondarenko M, Cortès-Saladelafont E, Aparicio J, Cuadras D, Horvath G, Fons C, Artuch R, García-Cazorla À; Institut de Recerca Sant Joan de Déu Working Group
Dev Med Child Neurol 2022 Jul;64(7):915-923. Epub 2022 Jan 31 doi: 10.1111/dmcn.15140. PMID: 35833444
Verducci C, Friedman D, Donner E, Devinsky O
Neurology 2020 Apr 21;94(16):e1757-e1763. Epub 2020 Mar 26 doi: 10.1212/WNL.0000000000009295. PMID: 32217773Free PMC Article
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Tiwari D, Peariso K, Gross C
Dev Dyn 2018 Jan;247(1):94-110. Epub 2017 Oct 4 doi: 10.1002/dvdy.24582. PMID: 28850760Free PMC Article

Prognosis

Thiel M, Bamborschke D, Janzarik WG, Assmann B, Zittel S, Patzer S, Auhuber A, Opp J, Matzker E, Bevot A, Seeger J, van Baalen A, Stüve B, Brockmann K, Cirak S, Koy A
J Neurol Neurosurg Psychiatry 2023 Oct;94(10):806-815. Epub 2023 May 24 doi: 10.1136/jnnp-2022-330261. PMID: 37225406
El-Dib M, Abend NS, Austin T, Boylan G, Chock V, Cilio MR, Greisen G, Hellström-Westas L, Lemmers P, Pellicer A, Pressler RM, Sansevere A, Tsuchida T, Vanhatalo S, Wusthoff CJ; Newborn Brain Society Guidelines and Publications Committee
Pediatr Res 2023 Jul;94(1):64-73. Epub 2022 Dec 7 doi: 10.1038/s41390-022-02393-1. PMID: 36476747
Wang X, Cui D, Ding C, Chen C, Wang X, Fang F, Jin H, Ren X
Genes (Basel) 2022 May 19;13(5) doi: 10.3390/genes13050908. PMID: 35627293Free PMC Article
Pisani F, Spagnoli C
Handb Clin Neurol 2019;162:401-414. doi: 10.1016/B978-0-444-64029-1.00019-9. PMID: 31324322
Hafström M, Källén K, Serenius F, Maršál K, Rehn E, Drake H, Ådén U, Farooqi A, Thorngren-Jerneck K, Strömberg B
Pediatrics 2018 Jan;141(1) Epub 2017 Dec 8 doi: 10.1542/peds.2017-1433. PMID: 29222398

Clinical prediction guides

Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Thiel M, Bamborschke D, Janzarik WG, Assmann B, Zittel S, Patzer S, Auhuber A, Opp J, Matzker E, Bevot A, Seeger J, van Baalen A, Stüve B, Brockmann K, Cirak S, Koy A
J Neurol Neurosurg Psychiatry 2023 Oct;94(10):806-815. Epub 2023 May 24 doi: 10.1136/jnnp-2022-330261. PMID: 37225406
Haneder C, Stark B, Peherstorfer A, Gröppel G
Seizure 2022 Mar;96:95-97. Epub 2022 Feb 12 doi: 10.1016/j.seizure.2022.02.008. PMID: 35183031
Pisani F, Spagnoli C
Handb Clin Neurol 2019;162:401-414. doi: 10.1016/B978-0-444-64029-1.00019-9. PMID: 31324322
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article

Recent systematic reviews

Stefanos-Yakoub I, Wingeier K, Held U, Latal B, Wirrell E, Smith ML, Ramantani G
Epilepsia 2024 Feb;65(2):251-265. Epub 2023 Dec 9 doi: 10.1111/epi.17834. PMID: 38031640
Baak LM, van der Aa NE, Verhagen AAE, Dudink J, Groenendaal F, Nijboer CHA, Benders MJNL, Wagenaar N
Pediatr Res 2023 Jul;94(1):20-33. Epub 2022 Dec 27 doi: 10.1038/s41390-022-02433-w. PMID: 36575364
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Bromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ, Tudur Smith C, Marson AG
Cochrane Database Syst Rev 2014 Oct 30;2014(10):CD010236. doi: 10.1002/14651858.CD010236.pub2. PMID: 25354543Free PMC Article

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