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Developmental and epileptic encephalopathy 97(DEE97)

MedGen UID:
1794209
Concept ID:
C5561999
Disease or Syndrome
Synonym: DEE97
 
Gene (location): CELF2 (10p14)
 
Monarch Initiative: MONDO:0030453
OMIM®: 619561

Definition

Developmental and epileptic encephalopathy-97 (DEE97) is characterized by developmental delay, epileptic encephalopathy, and impaired intellectual development. Other clinical features may include autistic features and hypotonia. For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Stereotypical hand wringing
MedGen UID:
646835
Concept ID:
C0562479
Finding
Habitual clasping and wringing of the hands in the middle of the body, similar to a hand-washing movement.
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).
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.
Epileptic spasm
MedGen UID:
315948
Concept ID:
C1527366
Disease or Syndrome
A sudden flexion, extension, or mixed extension-flexion of predominantly proximal and truncal muscles that is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure. Limited forms may occur
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
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.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Delayed ability to roll over
MedGen UID:
1718874
Concept ID:
C5397980
Finding
Delayed achievement of the ability to roll front to back and back to front.
Delayed ability to crawl
MedGen UID:
1772845
Concept ID:
C5421628
Finding
A failure to achieve the ability to crawl at an appropriate developmental stage. Normal infant motor development is marked by a series of postural milestones including learning to crawl on hands and knees between the ages of 6 and 10 months.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

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
Johannesen KM, Liu Y, Koko M, Gjerulfsen CE, Sonnenberg L, Schubert J, Fenger CD, Eltokhi A, Rannap M, Koch NA, Lauxmann S, Krüger J, Kegele J, Canafoglia L, Franceschetti S, Mayer T, Rebstock J, Zacher P, Ruf S, Alber M, Sterbova K, Lassuthová P, Vlckova M, Lemke JR, Platzer K, Krey I, Heine C, Wieczorek D, Kroell-Seger J, Lund C, Klein KM, Au PYB, Rho JM, Ho AW, Masnada S, Veggiotti P, Giordano L, Accorsi P, Hoei-Hansen CE, Striano P, Zara F, Verhelst H, Verhoeven JS, Braakman HMH, van der Zwaag B, Harder AVE, Brilstra E, Pendziwiat M, Lebon S, Vaccarezza M, Le NM, Christensen J, Grønborg S, Scherer SW, Howe J, Fazeli W, Howell KB, Leventer R, Stutterd C, Walsh S, Gerard M, Gerard B, Matricardi S, Bonardi CM, Sartori S, Berger A, Hoffman-Zacharska D, Mastrangelo M, Darra F, Vøllo A, Motazacker MM, Lakeman P, Nizon M, Betzler C, Altuzarra C, Caume R, Roubertie A, Gélisse P, Marini C, Guerrini R, Bilan F, Tibussek D, Koch-Hogrebe M, Perry MS, Ichikawa S, Dadali E, Sharkov A, Mishina I, Abramov M, Kanivets I, Korostelev S, Kutsev S, Wain KE, Eisenhauer N, Wagner M, Savatt JM, Müller-Schlüter K, Bassan H, Borovikov A, Nassogne MC, Destrée A, Schoonjans AS, Meuwissen M, Buzatu M, Jansen A, Scalais E, Srivastava S, Tan WH, Olson HE, Loddenkemper T, Poduri A, Helbig KL, Helbig I, Fitzgerald MP, Goldberg EM, Roser T, Borggraefe I, Brünger T, May P, Lal D, Lederer D, Rubboli G, Heyne HO, Lesca G, Hedrich UBS, Benda J, Gardella E, Lerche H, Møller RS
Brain 2022 Sep 14;145(9):2991-3009. doi: 10.1093/brain/awab321. PMID: 34431999Free 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

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
Johannesen KM, Liu Y, Koko M, Gjerulfsen CE, Sonnenberg L, Schubert J, Fenger CD, Eltokhi A, Rannap M, Koch NA, Lauxmann S, Krüger J, Kegele J, Canafoglia L, Franceschetti S, Mayer T, Rebstock J, Zacher P, Ruf S, Alber M, Sterbova K, Lassuthová P, Vlckova M, Lemke JR, Platzer K, Krey I, Heine C, Wieczorek D, Kroell-Seger J, Lund C, Klein KM, Au PYB, Rho JM, Ho AW, Masnada S, Veggiotti P, Giordano L, Accorsi P, Hoei-Hansen CE, Striano P, Zara F, Verhelst H, Verhoeven JS, Braakman HMH, van der Zwaag B, Harder AVE, Brilstra E, Pendziwiat M, Lebon S, Vaccarezza M, Le NM, Christensen J, Grønborg S, Scherer SW, Howe J, Fazeli W, Howell KB, Leventer R, Stutterd C, Walsh S, Gerard M, Gerard B, Matricardi S, Bonardi CM, Sartori S, Berger A, Hoffman-Zacharska D, Mastrangelo M, Darra F, Vøllo A, Motazacker MM, Lakeman P, Nizon M, Betzler C, Altuzarra C, Caume R, Roubertie A, Gélisse P, Marini C, Guerrini R, Bilan F, Tibussek D, Koch-Hogrebe M, Perry MS, Ichikawa S, Dadali E, Sharkov A, Mishina I, Abramov M, Kanivets I, Korostelev S, Kutsev S, Wain KE, Eisenhauer N, Wagner M, Savatt JM, Müller-Schlüter K, Bassan H, Borovikov A, Nassogne MC, Destrée A, Schoonjans AS, Meuwissen M, Buzatu M, Jansen A, Scalais E, Srivastava S, Tan WH, Olson HE, Loddenkemper T, Poduri A, Helbig KL, Helbig I, Fitzgerald MP, Goldberg EM, Roser T, Borggraefe I, Brünger T, May P, Lal D, Lederer D, Rubboli G, Heyne HO, Lesca G, Hedrich UBS, Benda J, Gardella E, Lerche H, Møller RS
Brain 2022 Sep 14;145(9):2991-3009. doi: 10.1093/brain/awab321. PMID: 34431999Free PMC Article
Cohen NT, Cross JH, Arzimanoglou A, Berkovic SF, Kerrigan JF, Miller IP, Webster E, Soeby L, Cukiert A, Hesdorffer DK, Kroner BL, Saper CB, Schulze-Bonhage A, Gaillard WD; Hypothalamic Hamartoma Writing Group
Neurology 2021 Nov 2;97(18):864-873. Epub 2021 Oct 4 doi: 10.1212/WNL.0000000000012773. PMID: 34607926Free 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
Alam S, Lux AL
Arch Dis Child 2012 Nov;97(11):985-92. Epub 2012 Sep 8 doi: 10.1136/archdischild-2011-301119. PMID: 22962318

Diagnosis

Cohen NT, Cross JH, Arzimanoglou A, Berkovic SF, Kerrigan JF, Miller IP, Webster E, Soeby L, Cukiert A, Hesdorffer DK, Kroner BL, Saper CB, Schulze-Bonhage A, Gaillard WD; Hypothalamic Hamartoma Writing Group
Neurology 2021 Nov 2;97(18):864-873. Epub 2021 Oct 4 doi: 10.1212/WNL.0000000000012773. PMID: 34607926Free PMC Article
Buers I, Persico I, Schöning L, Nitschke Y, Di Rocco M, Loi A, Sahi PK, Utine GE, Bayraktar-Tanyeri B, Zampino G, Crisponi G, Rutsch F, Crisponi L
Clin Genet 2020 Jan;97(1):209-221. Epub 2019 Sep 16 doi: 10.1111/cge.13639. PMID: 31497877
Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, Leonard H, Cross JH, Devinsky O, Benke TA
Pediatr Neurol 2019 Aug;97:18-25. Epub 2019 Feb 23 doi: 10.1016/j.pediatrneurol.2019.02.015. PMID: 30928302Free PMC Article
Carecchio M, Mencacci NE
Curr Neurol Neurosci Rep 2017 Oct 30;17(12):97. doi: 10.1007/s11910-017-0806-2. PMID: 29086067Free PMC Article
Alam S, Lux AL
Arch Dis Child 2012 Nov;97(11):985-92. Epub 2012 Sep 8 doi: 10.1136/archdischild-2011-301119. PMID: 22962318

Therapy

Johannesen KM, Liu Y, Koko M, Gjerulfsen CE, Sonnenberg L, Schubert J, Fenger CD, Eltokhi A, Rannap M, Koch NA, Lauxmann S, Krüger J, Kegele J, Canafoglia L, Franceschetti S, Mayer T, Rebstock J, Zacher P, Ruf S, Alber M, Sterbova K, Lassuthová P, Vlckova M, Lemke JR, Platzer K, Krey I, Heine C, Wieczorek D, Kroell-Seger J, Lund C, Klein KM, Au PYB, Rho JM, Ho AW, Masnada S, Veggiotti P, Giordano L, Accorsi P, Hoei-Hansen CE, Striano P, Zara F, Verhelst H, Verhoeven JS, Braakman HMH, van der Zwaag B, Harder AVE, Brilstra E, Pendziwiat M, Lebon S, Vaccarezza M, Le NM, Christensen J, Grønborg S, Scherer SW, Howe J, Fazeli W, Howell KB, Leventer R, Stutterd C, Walsh S, Gerard M, Gerard B, Matricardi S, Bonardi CM, Sartori S, Berger A, Hoffman-Zacharska D, Mastrangelo M, Darra F, Vøllo A, Motazacker MM, Lakeman P, Nizon M, Betzler C, Altuzarra C, Caume R, Roubertie A, Gélisse P, Marini C, Guerrini R, Bilan F, Tibussek D, Koch-Hogrebe M, Perry MS, Ichikawa S, Dadali E, Sharkov A, Mishina I, Abramov M, Kanivets I, Korostelev S, Kutsev S, Wain KE, Eisenhauer N, Wagner M, Savatt JM, Müller-Schlüter K, Bassan H, Borovikov A, Nassogne MC, Destrée A, Schoonjans AS, Meuwissen M, Buzatu M, Jansen A, Scalais E, Srivastava S, Tan WH, Olson HE, Loddenkemper T, Poduri A, Helbig KL, Helbig I, Fitzgerald MP, Goldberg EM, Roser T, Borggraefe I, Brünger T, May P, Lal D, Lederer D, Rubboli G, Heyne HO, Lesca G, Hedrich UBS, Benda J, Gardella E, Lerche H, Møller RS
Brain 2022 Sep 14;145(9):2991-3009. doi: 10.1093/brain/awab321. PMID: 34431999Free PMC Article
Guerrini R, Balestrini S, Wirrell EC, Walker MC
Neurology 2021 Oct 26;97(17):817-831. Epub 2021 Sep 7 doi: 10.1212/WNL.0000000000012744. PMID: 34493617Free PMC Article
Mesraoua B, Deleu D, Kullmann DM, Shetty AK, Boon P, Perucca E, Mikati MA, Asadi-Pooya AA
Epilepsy Behav 2019 Aug;97:282-290. Epub 2019 Jul 6 doi: 10.1016/j.yebeh.2019.04.042. PMID: 31284159
Olson HE, Demarest ST, Pestana-Knight EM, Swanson LC, Iqbal S, Lal D, Leonard H, Cross JH, Devinsky O, Benke TA
Pediatr Neurol 2019 Aug;97:18-25. Epub 2019 Feb 23 doi: 10.1016/j.pediatrneurol.2019.02.015. PMID: 30928302Free 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

Prognosis

Johannesen KM, Liu Y, Koko M, Gjerulfsen CE, Sonnenberg L, Schubert J, Fenger CD, Eltokhi A, Rannap M, Koch NA, Lauxmann S, Krüger J, Kegele J, Canafoglia L, Franceschetti S, Mayer T, Rebstock J, Zacher P, Ruf S, Alber M, Sterbova K, Lassuthová P, Vlckova M, Lemke JR, Platzer K, Krey I, Heine C, Wieczorek D, Kroell-Seger J, Lund C, Klein KM, Au PYB, Rho JM, Ho AW, Masnada S, Veggiotti P, Giordano L, Accorsi P, Hoei-Hansen CE, Striano P, Zara F, Verhelst H, Verhoeven JS, Braakman HMH, van der Zwaag B, Harder AVE, Brilstra E, Pendziwiat M, Lebon S, Vaccarezza M, Le NM, Christensen J, Grønborg S, Scherer SW, Howe J, Fazeli W, Howell KB, Leventer R, Stutterd C, Walsh S, Gerard M, Gerard B, Matricardi S, Bonardi CM, Sartori S, Berger A, Hoffman-Zacharska D, Mastrangelo M, Darra F, Vøllo A, Motazacker MM, Lakeman P, Nizon M, Betzler C, Altuzarra C, Caume R, Roubertie A, Gélisse P, Marini C, Guerrini R, Bilan F, Tibussek D, Koch-Hogrebe M, Perry MS, Ichikawa S, Dadali E, Sharkov A, Mishina I, Abramov M, Kanivets I, Korostelev S, Kutsev S, Wain KE, Eisenhauer N, Wagner M, Savatt JM, Müller-Schlüter K, Bassan H, Borovikov A, Nassogne MC, Destrée A, Schoonjans AS, Meuwissen M, Buzatu M, Jansen A, Scalais E, Srivastava S, Tan WH, Olson HE, Loddenkemper T, Poduri A, Helbig KL, Helbig I, Fitzgerald MP, Goldberg EM, Roser T, Borggraefe I, Brünger T, May P, Lal D, Lederer D, Rubboli G, Heyne HO, Lesca G, Hedrich UBS, Benda J, Gardella E, Lerche H, Møller RS
Brain 2022 Sep 14;145(9):2991-3009. doi: 10.1093/brain/awab321. PMID: 34431999Free PMC Article
Guerrini R, Balestrini S, Wirrell EC, Walker MC
Neurology 2021 Oct 26;97(17):817-831. Epub 2021 Sep 7 doi: 10.1212/WNL.0000000000012744. PMID: 34493617Free PMC Article
Liu Q, Ma J, Yu G, Zhang Q, Zhu Y, Wang R, Yu H, Liu C, Sun Y, Wang W, Wang S, Ji T, Li M, Liu X, Jiang Y, Cai L, Wu Y
Seizure 2021 Nov;92:29-35. Epub 2021 Aug 14 doi: 10.1016/j.seizure.2021.08.006. PMID: 34416421
Kim HJ, Yang D, Kim SH, Kim B, Kim HD, Lee JS, Choi JR, Lee ST, Kang HC
Epileptic Disord 2020 Oct 1;22(5):563-570. doi: 10.1684/epd.2020.1199. PMID: 33000761
Alam S, Lux AL
Arch Dis Child 2012 Nov;97(11):985-92. Epub 2012 Sep 8 doi: 10.1136/archdischild-2011-301119. PMID: 22962318

Clinical prediction guides

Cloppenborg T, van Schooneveld M, Hagemann A, Hopf JL, Kalbhenn T, Otte WM, Polster T, Bien CG, Braun KPJ
Neurology 2022 Jan 18;98(3):e225-e235. Epub 2021 Nov 18 doi: 10.1212/WNL.0000000000013065. PMID: 34795046
Guerrini R, Balestrini S, Wirrell EC, Walker MC
Neurology 2021 Oct 26;97(17):817-831. Epub 2021 Sep 7 doi: 10.1212/WNL.0000000000012744. PMID: 34493617Free PMC Article
Liu Q, Ma J, Yu G, Zhang Q, Zhu Y, Wang R, Yu H, Liu C, Sun Y, Wang W, Wang S, Ji T, Li M, Liu X, Jiang Y, Cai L, Wu Y
Seizure 2021 Nov;92:29-35. Epub 2021 Aug 14 doi: 10.1016/j.seizure.2021.08.006. PMID: 34416421
Kim HJ, Yang D, Kim SH, Kim B, Kim HD, Lee JS, Choi JR, Lee ST, Kang HC
Epileptic Disord 2020 Oct 1;22(5):563-570. doi: 10.1684/epd.2020.1199. PMID: 33000761
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

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
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
Nevalainen O, Ansakorpi H, Simola M, Raitanen J, Isojärvi J, Artama M, Auvinen A
Neurology 2014 Nov 18;83(21):1968-77. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001005. PMID: 25339211

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