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Developmental and epileptic encephalopathy, 65(EIEE65; DEE65)

MedGen UID:
1634676
Concept ID:
C4693925
Disease or Syndrome
Synonym: EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 65
 
Gene (location): CYFIP2 (5q33.3)
 
Monarch Initiative: MONDO:0033374
OMIM®: 618008

Definition

Developmental and epileptic encephalopathy-65 (DEE65) is characterized by onset of intractable seizures of various types usually within the first months or years of life, severe to profound psychomotor developmental delay, and mild facial dysmorphism (summary by Nakashima et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Plagiocephaly
MedGen UID:
1825944
Concept ID:
C2081594
Finding
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.

Professional guidelines

PubMed

D'Gama AM, Mulhern S, Sheidley BR, Boodhoo F, Buts S, Chandler NJ, Cobb J, Curtis M, Higginbotham EJ, Holland J, Khan T, Koh J, Liang NSY, McRae L, Nesbitt SE, Oby BT, Paternoster B, Patton A, Rose G, Scotchman E, Valentine R, Wiltrout KN; Gene-STEPS Study Group; IPCHiP Executive Committee, Hayeems RZ, Jain P, Lunke S, Marshall CR, Rockowitz S, Sebire NJ, Stark Z, White SM, Chitty LS, Cross JH, Scheffer IE, Chau V, Costain G, Poduri A, Howell KB, McTague A
Lancet Neurol 2023 Sep;22(9):812-825. doi: 10.1016/S1474-4422(23)00246-6. PMID: 37596007
Liu W, Cheng M, Zhu Y, Chen Y, Yang Y, Chen H, Niu X, Tian X, Yang X, Zhang Y
Dev Med Child Neurol 2023 Apr;65(4):534-543. Epub 2022 Sep 29 doi: 10.1111/dmcn.15414. PMID: 36175372
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

Recent clinical studies

Etiology

Poke G, Stanley J, Scheffer IE, Sadleir LG
Neurology 2023 Mar 28;100(13):e1363-e1375. Epub 2022 Dec 29 doi: 10.1212/WNL.0000000000206758. PMID: 36581463Free PMC Article
Lehner J, Frueh JS, Datta AN
Sleep Med Rev 2022 Oct;65:101689. Epub 2022 Aug 17 doi: 10.1016/j.smrv.2022.101689. PMID: 36037570
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A
JAMA Neurol 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829. PMID: 35499850Free PMC Article
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free 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

Diagnosis

Poke G, Stanley J, Scheffer IE, Sadleir LG
Neurology 2023 Mar 28;100(13):e1363-e1375. Epub 2022 Dec 29 doi: 10.1212/WNL.0000000000206758. PMID: 36581463Free PMC Article
Lehner J, Frueh JS, Datta AN
Sleep Med Rev 2022 Oct;65:101689. Epub 2022 Aug 17 doi: 10.1016/j.smrv.2022.101689. PMID: 36037570
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A
JAMA Neurol 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829. PMID: 35499850Free PMC Article
Coursimault J, Guerrot AM, Morrow MM, Schramm C, Zamora FM, Shanmugham A, Liu S, Zou F, Bilan F, Le Guyader G, Bruel AL, Denommé-Pichon AS, Faivre L, Tran Mau-Them F, Tessarech M, Colin E, El Chehadeh S, Gérard B, Schaefer E, Cogne B, Isidor B, Nizon M, Doummar D, Valence S, Héron D, Keren B, Mignot C, Coutton C, Devillard F, Alaix AS, Amiel J, Colleaux L, Munnich A, Poirier K, Rio M, Rondeau S, Barcia G, Callewaert B, Dheedene A, Kumps C, Vergult S, Menten B, Chung WK, Hernan R, Larson A, Nori K, Stewart S, Wheless J, Kresge C, Pletcher BA, Caumes R, Smol T, Sigaudy S, Coubes C, Helm M, Smith R, Morrison J, Wheeler PG, Kritzer A, Jouret G, Afenjar A, Deleuze JF, Olaso R, Boland A, Poitou C, Frebourg T, Houdayer C, Saugier-Veber P, Nicolas G, Lecoquierre F
Hum Genet 2022 Jan;141(1):65-80. Epub 2021 Nov 8 doi: 10.1007/s00439-021-02383-z. PMID: 34748075
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article

Therapy

Peariso K, Arya R, Glauser T, Abend NS, Barcia Aguilar C, Amengual-Gual M, Anderson A, Appavu BL, Brenton JN, Carpenter J, Chapman KE, Clark J, Gaillard WD, Gaínza-Lein M, Goldstein J, Goodkin H, Grinspan Z, Guerriero RM, Horn PS, Huh L, Kahoud R, Kelley SA, Kossoff EH, Kapur K, Lai YC, Marquis BO, McDonough T, Mikati MA, Morgan L, Novotny E, Ostendorf AP, Payne ET, Piantino J, Riviello J, Sands T, Stafstrom CE, Tasker RC, Tchapyjnikov D, Vasquez A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; for Pediatric Status Epilepticus Research Group (pSERG)
Neurology 2023 Aug 1;101(5):e546-e557. Epub 2023 Jun 9 doi: 10.1212/WNL.0000000000207472. PMID: 37295955Free PMC Article
Lehner J, Frueh JS, Datta AN
Sleep Med Rev 2022 Oct;65:101689. Epub 2022 Aug 17 doi: 10.1016/j.smrv.2022.101689. PMID: 36037570
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A
JAMA Neurol 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829. PMID: 35499850Free PMC Article
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free 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

Prognosis

Peariso K, Arya R, Glauser T, Abend NS, Barcia Aguilar C, Amengual-Gual M, Anderson A, Appavu BL, Brenton JN, Carpenter J, Chapman KE, Clark J, Gaillard WD, Gaínza-Lein M, Goldstein J, Goodkin H, Grinspan Z, Guerriero RM, Horn PS, Huh L, Kahoud R, Kelley SA, Kossoff EH, Kapur K, Lai YC, Marquis BO, McDonough T, Mikati MA, Morgan L, Novotny E, Ostendorf AP, Payne ET, Piantino J, Riviello J, Sands T, Stafstrom CE, Tasker RC, Tchapyjnikov D, Vasquez A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; for Pediatric Status Epilepticus Research Group (pSERG)
Neurology 2023 Aug 1;101(5):e546-e557. Epub 2023 Jun 9 doi: 10.1212/WNL.0000000000207472. PMID: 37295955Free PMC Article
Scheffer IE, Bennett CA, Gill D, de Silva MG, Boggs K, Marum J, Baker N; Australian Genomics DEE Flagship, Palmer EE, Howell KB
Dev Med Child Neurol 2023 Jan;65(1):50-57. Epub 2022 Jun 14 doi: 10.1111/dmcn.15308. PMID: 35701389Free PMC Article
Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Dalla Bernardina B, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffler M, Lerche H, Lesca G, Lewis-Smith D, Marini C, Marjanovic D, Mazzola L, McKeown Ruggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S
Neurology 2022 Jul 19;99(3):e221-e233. Epub 2022 Jun 3 doi: 10.1212/WNL.0000000000200715. PMID: 35851549Free PMC Article
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article
Halász P, Kelemen A, Rosdy B, Rásonyi G, Clemens B, Szűcs A
Seizure 2019 Feb;65:31-41. Epub 2018 Dec 21 doi: 10.1016/j.seizure.2018.12.003. PMID: 30605881

Clinical prediction guides

Strzelczyk A, Lagae L, Wilmshurst JM, Brunklaus A, Striano P, Rosenow F, Schubert-Bast S
Epilepsia Open 2023 Dec;8(4):1256-1270. Epub 2023 Oct 11 doi: 10.1002/epi4.12832. PMID: 37750463Free PMC Article
Peariso K, Arya R, Glauser T, Abend NS, Barcia Aguilar C, Amengual-Gual M, Anderson A, Appavu BL, Brenton JN, Carpenter J, Chapman KE, Clark J, Gaillard WD, Gaínza-Lein M, Goldstein J, Goodkin H, Grinspan Z, Guerriero RM, Horn PS, Huh L, Kahoud R, Kelley SA, Kossoff EH, Kapur K, Lai YC, Marquis BO, McDonough T, Mikati MA, Morgan L, Novotny E, Ostendorf AP, Payne ET, Piantino J, Riviello J, Sands T, Stafstrom CE, Tasker RC, Tchapyjnikov D, Vasquez A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; for Pediatric Status Epilepticus Research Group (pSERG)
Neurology 2023 Aug 1;101(5):e546-e557. Epub 2023 Jun 9 doi: 10.1212/WNL.0000000000207472. PMID: 37295955Free PMC Article
Lehner J, Frueh JS, Datta AN
Sleep Med Rev 2022 Oct;65:101689. Epub 2022 Aug 17 doi: 10.1016/j.smrv.2022.101689. PMID: 36037570
Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Dalla Bernardina B, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffler M, Lerche H, Lesca G, Lewis-Smith D, Marini C, Marjanovic D, Mazzola L, McKeown Ruggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S
Neurology 2022 Jul 19;99(3):e221-e233. Epub 2022 Jun 3 doi: 10.1212/WNL.0000000000200715. PMID: 35851549Free PMC Article
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A
JAMA Neurol 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829. PMID: 35499850Free 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
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
Lehner J, Frueh JS, Datta AN
Sleep Med Rev 2022 Oct;65:101689. Epub 2022 Aug 17 doi: 10.1016/j.smrv.2022.101689. PMID: 36037570
Salvati A, Bonaventura E, Sesso G, Pasquariello R, Sicca F
Seizure 2021 Oct;91:425-436. Epub 2021 Jul 21 doi: 10.1016/j.seizure.2021.07.020. PMID: 34325301
Kuersten M, Tacke M, Gerstl L, Hoelz H, Stülpnagel CV, Borggraefe I
Eur J Med Genet 2020 Jan;63(1):103628. Epub 2019 Feb 14 doi: 10.1016/j.ejmg.2019.02.001. PMID: 30771507

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