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Developmental and epileptic encephalopathy, 68(EIEE68; DEE68)

MedGen UID:
1648479
Concept ID:
C4748688
Disease or Syndrome
Synonym: EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 68
 
Gene (location): TRAK1 (3p22.1)
 
Monarch Initiative: MONDO:0032598
OMIM®: 618201

Definition

Developmental and epileptic encephalopathy-68 (DEE68) is an autosomal recessive neurologic disorder characterized by onset of twitching and/or myoclonic jerks in infancy. The disorder progresses to refractory generalized tonic-clonic seizures, often resulting in status epilepticus, loss of developmental milestones, and early death. Other features include delayed development, axial hypotonia, spasticity of the limbs, and clonus. Brain imaging may show cortical atrophy (summary by Barel et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
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.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Muscle fibrillation
MedGen UID:
65418
Concept ID:
C0231531
Finding
Fine, rapid twitching of individual muscle fibers with little or no movement of the muscle as a whole as ascertained by electromyography (EMG). If a motor neuron or its axon is destroyed, the muscle fibers it innervates undergo denervation atrophy. This leads to hypersensitivity of individual muscle fibers to acetyl choline so that they may contract spontaneously. Isolated activity of individual muscle fibers is generally so fine it cannot be seen through the intact skin, although it can be recorded as a short-duration spike in the EMG.
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.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.

Professional guidelines

PubMed

Engel C, Valence S, Delplancq G, Maroofian R, Accogli A, Agolini E, Alkuraya FS, Baglioni V, Bagnasco I, Becmeur-Lefebvre M, Bertini E, Borggraefe I, Brischoux-Boucher E, Bruel AL, Brusco A, Bubshait DK, Cabrol C, Cilio MR, Cornet MC, Coubes C, Danhaive O, Delague V, Denommé-Pichon AS, Di Giacomo MC, Doco-Fenzy M, Engels H, Cremer K, Gérard M, Gleeson JG, Heron D, Goffeney J, Guimier A, Harms FL, Houlden H, Iacomino M, Kaiyrzhanov R, Kamien B, Karimiani EG, Kraus D, Kuentz P, Kutsche K, Lederer D, Massingham L, Mignot C, Morris-Rosendahl D, Nagarajan L, Odent S, Ormières C, Partlow JN, Pasquier L, Penney L, Philippe C, Piccolo G, Poulton C, Putoux A, Rio M, Rougeot C, Salpietro V, Scheffer I, Schneider A, Srivastava S, Straussberg R, Striano P, Valente EM, Venot P, Villard L, Vitobello A, Wagner J, Wagner M, Zaki MS, Zara F, Lesca G, Yassaee VR, Miryounesi M, Hashemi-Gorji F, Beiraghi M, Ashrafzadeh F, Galehdari H, Walsh C, Novelli A, Tacke M, Sadykova D, Maidyrov Y, Koneev K, Shashkin C, Capra V, Zamani M, Van Maldergem L, Burglen L, Piard J
Eur J Hum Genet 2023 Sep;31(9):1023-1031. Epub 2023 Jun 21 doi: 10.1038/s41431-023-01410-z. PMID: 37344571Free PMC Article
Barcia Aguilar C, Amengual-Gual M, Sánchez Fernández I, Abend NS, Anderson A, Appavu B, Arya R, Brenton JN, Carpenter JL, Chapman KE, Clark J, Farias-Moeller R, Gaillard WD, Gaínza-Lein M, Glauser T, Goldstein JL, Goodkin HP, Guerriero RM, Huh L, Lai YC, McDonough TL, Mikati MA, Morgan LA, Novotny EJ, Ostendorf A, Payne ET, Peariso K, Piantino J, Riviello J, Sannagowdara K, Sheehan T, Sands TT, Tasker RC, Tchapyjnikov D, Topjian AA, Vasquez A, Wainwright MS, Wilfong AA, Williams K, Loddenkemper T; pSERG
Pediatr Neurol 2021 Jul;120:71-79. Epub 2021 Mar 26 doi: 10.1016/j.pediatrneurol.2021.03.009. PMID: 34022752
Strzelczyk A, Schubert-Bast S
CNS Drugs 2021 Jan;35(1):61-83. Epub 2021 Jan 21 doi: 10.1007/s40263-020-00784-8. PMID: 33479851Free PMC Article

Recent clinical studies

Etiology

Robertsson Grossmann K, Eriksson Westblad M, Blennow M, Lindström K
Arch Dis Child Fetal Neonatal Ed 2023 May;108(3):295-301. Epub 2022 Dec 9 doi: 10.1136/archdischild-2022-324418. PMID: 36600485Free PMC Article
Strzelczyk A, Schubert-Bast S
CNS Drugs 2021 Jan;35(1):61-83. Epub 2021 Jan 21 doi: 10.1007/s40263-020-00784-8. PMID: 33479851Free PMC Article
Vlaskamp DRM, Shaw BJ, Burgess R, Mei D, Montomoli M, Xie H, Myers CT, Bennett MF, XiangWei W, Williams D, Maas SM, Brooks AS, Mancini GMS, van de Laar IMBH, van Hagen JM, Ware TL, Webster RI, Malone S, Berkovic SF, Kalnins RM, Sicca F, Korenke GC, van Ravenswaaij-Arts CMA, Hildebrand MS, Mefford HC, Jiang Y, Guerrini R, Scheffer IE
Neurology 2019 Jan 8;92(2):e96-e107. Epub 2018 Dec 12 doi: 10.1212/WNL.0000000000006729. PMID: 30541864Free PMC Article
Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, Löscher W
Acta Neuropathol 2016 Feb;131(2):211-234. Epub 2015 Sep 30 doi: 10.1007/s00401-015-1481-5. PMID: 26423537Free PMC Article
Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshé SL, Shinnar S
Pediatr Neurol 2013 Jan;48(1):42-7. doi: 10.1016/j.pediatrneurol.2012.09.006. PMID: 23290019

Diagnosis

Suthar M, Mishra D, Juneja M, Kalra BS, Arya Y
Indian Pediatr 2024 Aug 15;61(8):768-770. Epub 2024 Jul 12 PMID: 39001784
Eriksson MH, Ripart M, Piper RJ, Moeller F, Das KB, Eltze C, Cooray G, Booth J, Whitaker KJ, Chari A, Martin Sanfilippo P, Perez Caballero A, Menzies L, McTague A, Tisdall MM, Cross JH, Baldeweg T, Adler S, Wagstyl K
Epilepsia 2023 Aug;64(8):2014-2026. Epub 2023 Jun 16 doi: 10.1111/epi.17637. PMID: 37129087Free PMC Article
Eom S, Dezort C, Fisher B, Zelko F, Berg AT
Epilepsy Behav 2015 May;46:84-7. Epub 2015 May 7 doi: 10.1016/j.yebeh.2015.04.023. PMID: 25958227
Sweetman LL, Ng YT, Kerrigan JF
Clin Pediatr (Phila) 2007 May;46(4):325-8. doi: 10.1177/0009922806295400. PMID: 17475990
Grigg-Damberger MM, Coker SB, Halsey CL, Anderson CL
Pediatr Neurol 1989 Mar-Apr;5(2):84-92. doi: 10.1016/0887-8994(89)90032-5. PMID: 2469427

Therapy

Strzelczyk A, Schubert-Bast S
CNS Drugs 2021 Jan;35(1):61-83. Epub 2021 Jan 21 doi: 10.1007/s40263-020-00784-8. PMID: 33479851Free PMC Article
Vlaskamp DRM, Shaw BJ, Burgess R, Mei D, Montomoli M, Xie H, Myers CT, Bennett MF, XiangWei W, Williams D, Maas SM, Brooks AS, Mancini GMS, van de Laar IMBH, van Hagen JM, Ware TL, Webster RI, Malone S, Berkovic SF, Kalnins RM, Sicca F, Korenke GC, van Ravenswaaij-Arts CMA, Hildebrand MS, Mefford HC, Jiang Y, Guerrini R, Scheffer IE
Neurology 2019 Jan 8;92(2):e96-e107. Epub 2018 Dec 12 doi: 10.1212/WNL.0000000000006729. PMID: 30541864Free PMC Article
Qadir AA, Obringer E, Hageman J, Marcuccilli C
J Child Neurol 2017 Sep;32(10):876-879. Epub 2017 Jun 12 doi: 10.1177/0883073817713906. PMID: 28604149
Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshé SL, Shinnar S
Pediatr Neurol 2013 Jan;48(1):42-7. doi: 10.1016/j.pediatrneurol.2012.09.006. PMID: 23290019
Korff CM, Parvex P, Cimasoni L, Wilhelm-Bals A, Hampe CS, Schwitzgebel VM, Michel M, Siegrist CA, Lalive PH, Seeck M
Arch Neurol 2011 Aug;68(8):1065-8. doi: 10.1001/archneurol.2011.177. PMID: 21825244

Prognosis

Eriksson MH, Ripart M, Piper RJ, Moeller F, Das KB, Eltze C, Cooray G, Booth J, Whitaker KJ, Chari A, Martin Sanfilippo P, Perez Caballero A, Menzies L, McTague A, Tisdall MM, Cross JH, Baldeweg T, Adler S, Wagstyl K
Epilepsia 2023 Aug;64(8):2014-2026. Epub 2023 Jun 16 doi: 10.1111/epi.17637. PMID: 37129087Free PMC Article
Khan M, Chari A, Seunarine K, Eltze C, Moeller F, D'Arco F, Thornton R, Das K, Boyd S, Helen Cross J, Zubair Tahir M, Tisdall MM
Clin Neurophysiol 2022 Jun;138:18-24. Epub 2022 Mar 22 doi: 10.1016/j.clinph.2022.03.012. PMID: 35364463
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
Eom S, Dezort C, Fisher B, Zelko F, Berg AT
Epilepsy Behav 2015 May;46:84-7. Epub 2015 May 7 doi: 10.1016/j.yebeh.2015.04.023. PMID: 25958227
Grigg-Damberger MM, Coker SB, Halsey CL, Anderson CL
Pediatr Neurol 1989 Mar-Apr;5(2):84-92. doi: 10.1016/0887-8994(89)90032-5. PMID: 2469427

Clinical prediction guides

Robertsson Grossmann K, Eriksson Westblad M, Blennow M, Lindström K
Arch Dis Child Fetal Neonatal Ed 2023 May;108(3):295-301. Epub 2022 Dec 9 doi: 10.1136/archdischild-2022-324418. PMID: 36600485Free PMC Article
Zhou Y, Su Y, Li S, Kennedy BC, Zhang DY, Bond AM, Sun Y, Jacob F, Lu L, Hu P, Viaene AN, Helbig I, Kessler SK, Lucas T, Salinas RD, Gu X, Chen HI, Wu H, Kleinman JE, Hyde TM, Nauen DW, Weinberger DR, Ming GL, Song H
Nature 2022 Jul;607(7919):527-533. Epub 2022 Jul 6 doi: 10.1038/s41586-022-04912-w. PMID: 35794479Free PMC Article
Khan M, Chari A, Seunarine K, Eltze C, Moeller F, D'Arco F, Thornton R, Das K, Boyd S, Helen Cross J, Zubair Tahir M, Tisdall MM
Clin Neurophysiol 2022 Jun;138:18-24. Epub 2022 Mar 22 doi: 10.1016/j.clinph.2022.03.012. PMID: 35364463
Strzelczyk A, Schubert-Bast S
CNS Drugs 2021 Jan;35(1):61-83. Epub 2021 Jan 21 doi: 10.1007/s40263-020-00784-8. PMID: 33479851Free PMC Article
Eom S, Dezort C, Fisher B, Zelko F, Berg AT
Epilepsy Behav 2015 May;46:84-7. Epub 2015 May 7 doi: 10.1016/j.yebeh.2015.04.023. PMID: 25958227

Recent systematic reviews

Fang C, Yang L, Xiao F, Yan K, Zhou W
Epilepsy Res 2024 May;202:107363. Epub 2024 Apr 17 doi: 10.1016/j.eplepsyres.2024.107363. PMID: 38636407
Peron A, Picot C, Jurek L, Nourredine M, Ripoche E, Ajiji P, Cucherat M, Cottin J
BMC Pregnancy Childbirth 2024 Feb 2;24(1):103. doi: 10.1186/s12884-023-06242-9. PMID: 38308208Free PMC Article
Frank NA, Greuter L, Guzman R, Soleman J
Childs Nerv Syst 2023 Mar;39(3):677-688. Epub 2022 Oct 11 doi: 10.1007/s00381-022-05699-x. PMID: 36219224
Iranmehr A, Dabbagh Ohadi MA, Chavoshi M, Jahanbakhshi A, Slavin KV
Neurosurg Focus 2022 Oct;53(4):E8. doi: 10.3171/2022.7.FOCUS22296. PMID: 36183177
Gerstl L, Willimsky E, Rémi C, Noachtar S, Borggräfe I, Tacke M
Clin Neuropharmacol 2021 Mar-Apr 01;44(2):39-46. doi: 10.1097/WNF.0000000000000435. PMID: 33605607

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