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Developmental and epileptic encephalopathy, 59(EIEE59; DEE59)

MedGen UID:
1633749
Concept ID:
C4693550
Disease or Syndrome
Synonym: Early infantile epileptic encephalopathy 59
 
Gene (location): GABBR2 (9q22.33)
 
Monarch Initiative: MONDO:0033368
OMIM®: 617904

Definition

Developmental and epileptic encephalopathy-59 (DEE59) is characterized by severe global developmental delay apparent in infancy with onset of various types of seizures in the first months of life (range 3 to 11 months). The seizures are usually refractory and are often associated with hypsarrhythmia on EEG, although brain imaging is usually normal. More severely affected individuals may be unable to speak or walk, have poor interaction, and require a feeding tube (summary by the EuroEPINOMICS-RES Consortium et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
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.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
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).
Focal clonic seizure
MedGen UID:
155749
Concept ID:
C0752323
Disease or Syndrome
A focal clonic seizure is a type of focal motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
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).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.

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
Batson S, Shankar R, Conry J, Boggs J, Radtke R, Mitchell S, Barion F, Murphy J, Danielson V
J Neurol 2022 Jun;269(6):2874-2891. Epub 2022 Jan 16 doi: 10.1007/s00415-022-10967-6. PMID: 35034187Free PMC Article
Khoo HM, Gotman J, Hall JA, Dubeau F
Curr Neurol Neurosci Rep 2020 Oct 30;20(12):59. doi: 10.1007/s11910-020-01082-y. PMID: 33123826

Recent clinical studies

Etiology

Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free 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
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group
Lancet 2018 Mar 17;391(10125):1085-1096. Epub 2018 Jan 26 doi: 10.1016/S0140-6736(18)30136-3. PMID: 29395273
Blumcke I, Spreafico R, Haaker G, Coras R, Kobow K, Bien CG, Pfäfflin M, Elger C, Widman G, Schramm J, Becker A, Braun KP, Leijten F, Baayen JC, Aronica E, Chassoux F, Hamer H, Stefan H, Rössler K, Thom M, Walker MC, Sisodiya SM, Duncan JS, McEvoy AW, Pieper T, Holthausen H, Kudernatsch M, Meencke HJ, Kahane P, Schulze-Bonhage A, Zentner J, Heiland DH, Urbach H, Steinhoff BJ, Bast T, Tassi L, Lo Russo G, Özkara C, Oz B, Krsek P, Vogelgesang S, Runge U, Lerche H, Weber Y, Honavar M, Pimentel J, Arzimanoglou A, Ulate-Campos A, Noachtar S, Hartl E, Schijns O, Guerrini R, Barba C, Jacques TS, Cross JH, Feucht M, Mühlebner A, Grunwald T, Trinka E, Winkler PA, Gil-Nagel A, Toledano Delgado R, Mayer T, Lutz M, Zountsas B, Garganis K, Rosenow F, Hermsen A, von Oertzen TJ, Diepgen TL, Avanzini G; EEBB Consortium
N Engl J Med 2017 Oct 26;377(17):1648-1656. doi: 10.1056/NEJMoa1703784. PMID: 29069555
Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M
JAMA 2013 Apr 24;309(16):1696-703. doi: 10.1001/jama.2013.2270. PMID: 23613074Free PMC Article

Diagnosis

Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free PMC Article
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
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
Blumcke I, Spreafico R, Haaker G, Coras R, Kobow K, Bien CG, Pfäfflin M, Elger C, Widman G, Schramm J, Becker A, Braun KP, Leijten F, Baayen JC, Aronica E, Chassoux F, Hamer H, Stefan H, Rössler K, Thom M, Walker MC, Sisodiya SM, Duncan JS, McEvoy AW, Pieper T, Holthausen H, Kudernatsch M, Meencke HJ, Kahane P, Schulze-Bonhage A, Zentner J, Heiland DH, Urbach H, Steinhoff BJ, Bast T, Tassi L, Lo Russo G, Özkara C, Oz B, Krsek P, Vogelgesang S, Runge U, Lerche H, Weber Y, Honavar M, Pimentel J, Arzimanoglou A, Ulate-Campos A, Noachtar S, Hartl E, Schijns O, Guerrini R, Barba C, Jacques TS, Cross JH, Feucht M, Mühlebner A, Grunwald T, Trinka E, Winkler PA, Gil-Nagel A, Toledano Delgado R, Mayer T, Lutz M, Zountsas B, Garganis K, Rosenow F, Hermsen A, von Oertzen TJ, Diepgen TL, Avanzini G; EEBB Consortium
N Engl J Med 2017 Oct 26;377(17):1648-1656. doi: 10.1056/NEJMoa1703784. PMID: 29069555
Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M
JAMA 2013 Apr 24;309(16):1696-703. doi: 10.1001/jama.2013.2270. PMID: 23613074Free PMC Article

Therapy

Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free 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
Trivisano M, Specchio N
Epilepsy Behav 2019 Dec;101(Pt B):106539. Epub 2019 Oct 31 doi: 10.1016/j.yebeh.2019.106539. PMID: 31678000
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group
Lancet 2018 Mar 17;391(10125):1085-1096. Epub 2018 Jan 26 doi: 10.1016/S0140-6736(18)30136-3. PMID: 29395273
Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M
JAMA 2013 Apr 24;309(16):1696-703. doi: 10.1001/jama.2013.2270. PMID: 23613074Free PMC Article

Prognosis

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
Oshino S, Tani N, Khoo HM, Kagitani-Shimono K, Nabatame S, Tominaga K, Yanagisawa T, Hirata M, Kishima H
Neurol Med Chir (Tokyo) 2023 May 15;63(5):173-178. Epub 2023 Apr 6 doi: 10.2176/jns-nmc.2022-0300. PMID: 37019652Free PMC Article
Boets S, Johannesen KM, Destree A, Manti F, Ramantani G, Lesca G, Vercueil L, Koenig MK, Striano P, Møller RS, Cooper E, Weckhuysen S
J Med Genet 2022 Jun;59(6):528-535. Epub 2021 Apr 2 doi: 10.1136/jmedgenet-2020-107449. PMID: 33811133
Trivisano M, Pietrafusa N, Terracciano A, Marini C, Mei D, Darra F, Accorsi P, Battaglia D, Caffi L, Canevini MP, Cappelletti S, Cesaroni E, de Palma L, Costa P, Cusmai R, Giordano L, Ferrari A, Freri E, Fusco L, Granata T, Martino T, Mastrangelo M, Bova SM, Parmeggiani L, Ragona F, Sicca F, Striano P, Specchio LM, Tondo I, Zambrelli E, Zamponi N, Zanus C, Boniver C, Vecchi M, Avolio C, Dalla Bernardina B, Bertini E, Guerrini R, Vigevano F, Specchio N
Epilepsia 2018 Dec;59(12):2260-2271. Epub 2018 Nov 19 doi: 10.1111/epi.14600. PMID: 30451291
Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M
JAMA 2013 Apr 24;309(16):1696-703. doi: 10.1001/jama.2013.2270. PMID: 23613074Free PMC Article

Clinical prediction guides

Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article
Liu X, Zhu Y, Liu Q, Zhang S, Wu P, Sun Y, Zhang J, Wang R, Ji T, Wang S, Liu X, Jiang Y, Cai L, Wu Y
Epilepsia Open 2023 Sep;8(3):898-911. Epub 2023 May 16 doi: 10.1002/epi4.12755. PMID: 37144544Free PMC Article
Oshino S, Tani N, Khoo HM, Kagitani-Shimono K, Nabatame S, Tominaga K, Yanagisawa T, Hirata M, Kishima H
Neurol Med Chir (Tokyo) 2023 May 15;63(5):173-178. Epub 2023 Apr 6 doi: 10.2176/jns-nmc.2022-0300. PMID: 37019652Free 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
Wyers L, Verheyen K, Ceulemans B, Schoonjans AS, Desloovere K, Van de Walle P, Hallemans A
Eur J Paediatr Neurol 2021 Nov;35:100-110. Epub 2021 Oct 15 doi: 10.1016/j.ejpn.2021.10.006. PMID: 34666230

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
Mazzone PP, Hogg KM, Weir CJ, Stephen J, Bhattacharya S, Richer S, Chin RFM
Seizure 2024 Apr;117:213-221. Epub 2024 Feb 29 doi: 10.1016/j.seizure.2024.02.014. PMID: 38484631
Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free PMC Article
Batson S, Shankar R, Conry J, Boggs J, Radtke R, Mitchell S, Barion F, Murphy J, Danielson V
J Neurol 2022 Jun;269(6):2874-2891. Epub 2022 Jan 16 doi: 10.1007/s00415-022-10967-6. PMID: 35034187Free PMC Article
Auvin S, Wirrell E, Donald KA, Berl M, Hartmann H, Valente KD, Van Bogaert P, Cross JH, Osawa M, Kanemura H, Aihara M, Guerreiro MM, Samia P, Vinayan KP, Smith ML, Carmant L, Kerr M, Hermann B, Dunn D, Wilmshurst JM
Epilepsia 2018 Oct;59(10):1867-1880. Epub 2018 Sep 3 doi: 10.1111/epi.14549. PMID: 30178479

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