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Developmental and epileptic encephalopathy, 61(EIEE61; DEE61)

MedGen UID:
1639392
Concept ID:
C4693688
Disease or Syndrome
Synonym: Early infantile epileptic encephalopathy 61
 
Gene (location): ADAM22 (7q21.12)
 
Monarch Initiative: MONDO:0033370
OMIM®: 617933

Definition

Developmental and epileptic encephalopathy-61 (DEE61) is an autosomal recessive neurologic disorder characterized by the onset of refractory seizures in the first months or years of life. There is profound global developmental delay with intellectual disability, inability to walk, poor voluntary movements, spasticity, microcephaly, cerebral atrophy, and dysmorphic facial features (summary by Muona et al., 2016). 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 characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
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.
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.
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Professional guidelines

PubMed

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
Lee S, Karp N, Zapata-Aldana E, Sadikovic B, Yang P, Balci TB, Prasad AN
Can J Neurol Sci 2021 Mar;48(2):233-244. Epub 2020 Aug 3 doi: 10.1017/cjn.2020.167. PMID: 32741404
DiBacco ML, Pop A, Salomons GS, Hanson E, Roullet JB, Gibson KM, Pearl PL
Neurology 2020 Nov 10;95(19):e2675-e2682. Epub 2020 Sep 4 doi: 10.1212/WNL.0000000000010730. PMID: 32887777Free PMC Article

Recent clinical studies

Etiology

Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free 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
Bar C, Kuchenbuch M, Barcia G, Schneider A, Jennesson M, Le Guyader G, Lesca G, Mignot C, Montomoli M, Parrini E, Isnard H, Rolland A, Keren B, Afenjar A, Dorison N, Sadleir LG, Breuillard D, Levy R, Rio M, Dupont S, Negrin S, Danieli A, Scalais E, De Saint Martin A, El Chehadeh S, Chelly J, Poisson A, Lebre AS, Nica A, Odent S, Sekhara T, Brankovic V, Goldenberg A, Vrielynck P, Lederer D, Maurey H, Terrone G, Besmond C, Hubert L, Berquin P, Billette de Villemeur T, Isidor B, Freeman JL, Mefford HC, Myers CT, Howell KB, Rodríguez-Sacristán Cascajo A, Meyer P, Genevieve D, Guët A, Doummar D, Durigneux J, van Dooren MF, de Wit MCY, Gerard M, Marey I, Munnich A, Guerrini R, Scheffer IE, Kabashi E, Nabbout R
Epilepsia 2020 Nov;61(11):2461-2473. Epub 2020 Sep 21 doi: 10.1111/epi.16679. PMID: 32954514
Rochtus A, Olson HE, Smith L, Keith LG, El Achkar C, Taylor A, Mahida S, Park M, Kelly M, Shain C, Rockowitz S, Rosen Sheidley B, Poduri A
Epilepsia 2020 Feb;61(2):249-258. Epub 2020 Jan 19 doi: 10.1111/epi.16427. PMID: 31957018Free PMC Article
Takata A, Nakashima M, Saitsu H, Mizuguchi T, Mitsuhashi S, Takahashi Y, Okamoto N, Osaka H, Nakamura K, Tohyama J, Haginoya K, Takeshita S, Kuki I, Okanishi T, Goto T, Sasaki M, Sakai Y, Miyake N, Miyatake S, Tsuchida N, Iwama K, Minase G, Sekiguchi F, Fujita A, Imagawa E, Koshimizu E, Uchiyama Y, Hamanaka K, Ohba C, Itai T, Aoi H, Saida K, Sakaguchi T, Den K, Takahashi R, Ikeda H, Yamaguchi T, Tsukamoto K, Yoshitomi S, Oboshi T, Imai K, Kimizu T, Kobayashi Y, Kubota M, Kashii H, Baba S, Iai M, Kira R, Hara M, Ohta M, Miyata Y, Miyata R, Takanashi JI, Matsui J, Yokochi K, Shimono M, Amamoto M, Takayama R, Hirabayashi S, Aiba K, Matsumoto H, Nabatame S, Shiihara T, Kato M, Matsumoto N
Nat Commun 2019 Jun 7;10(1):2506. doi: 10.1038/s41467-019-10482-9. PMID: 31175295Free PMC Article

Diagnosis

Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free PMC Article
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
Matricardi S, De Liso P, Freri E, Costa P, Castellotti B, Magri S, Gellera C, Granata T, Musante L, Lesca G, Oertel J, Craiu D, Hammer TB, Møller RS, Barisic N, Abou Jamra R, Polster T, Vigevano F, Marini C
Epilepsia 2020 Nov;61(11):2474-2485. Epub 2020 Oct 16 doi: 10.1111/epi.16699. PMID: 33063863
Rochtus A, Olson HE, Smith L, Keith LG, El Achkar C, Taylor A, Mahida S, Park M, Kelly M, Shain C, Rockowitz S, Rosen Sheidley B, Poduri A
Epilepsia 2020 Feb;61(2):249-258. Epub 2020 Jan 19 doi: 10.1111/epi.16427. PMID: 31957018Free PMC Article
Takata A, Nakashima M, Saitsu H, Mizuguchi T, Mitsuhashi S, Takahashi Y, Okamoto N, Osaka H, Nakamura K, Tohyama J, Haginoya K, Takeshita S, Kuki I, Okanishi T, Goto T, Sasaki M, Sakai Y, Miyake N, Miyatake S, Tsuchida N, Iwama K, Minase G, Sekiguchi F, Fujita A, Imagawa E, Koshimizu E, Uchiyama Y, Hamanaka K, Ohba C, Itai T, Aoi H, Saida K, Sakaguchi T, Den K, Takahashi R, Ikeda H, Yamaguchi T, Tsukamoto K, Yoshitomi S, Oboshi T, Imai K, Kimizu T, Kobayashi Y, Kubota M, Kashii H, Baba S, Iai M, Kira R, Hara M, Ohta M, Miyata Y, Miyata R, Takanashi JI, Matsui J, Yokochi K, Shimono M, Amamoto M, Takayama R, Hirabayashi S, Aiba K, Matsumoto H, Nabatame S, Shiihara T, Kato M, Matsumoto N
Nat Commun 2019 Jun 7;10(1):2506. doi: 10.1038/s41467-019-10482-9. PMID: 31175295Free PMC Article

Therapy

Sullivan J, Gunning B, Zafar M, Guerrini R, Gecz J, Kolc KL, Zhao Y, Gasior M, Aimetti AA, Samanta D
Epilepsy Res 2023 Mar;191:107112. Epub 2023 Feb 22 doi: 10.1016/j.eplepsyres.2023.107112. PMID: 36870093
Nissenkorn A, Kluger G, Schubert-Bast S, Bayat A, Bobylova M, Bonanni P, Ceulemans B, Coppola A, Di Bonaventura C, Feucht M, Fuchs A, Gröppel G, Heimer G, Herdt B, Kulikova S, Mukhin K, Nicassio S, Orsini A, Panagiotou M, Pringsheim M, Puest B, Pylaeva O, Ramantani G, Tsekoura M, Ricciardelli P, Lerman Sagie T, Stark B, Striano P, van Baalen A, De Wachter M, Cerulli Irelli E, Cuccurullo C, von Stülpnagel C, Russo A
Epilepsia 2023 Apr;64(4):866-874. Epub 2023 Feb 20 doi: 10.1111/epi.17530. PMID: 36734057
Kamaşak T, Serdaroğlu E, Yılmaz Ö, Kılıç BA, Polat BG, Erdoğan I, Yücel Şen AD, Özen N, Durgut BD, Yıldız N, Özkan Kart P, Dilber B, Arslan EA, Şahin S, Topçu Y, Gencpinar P, Serin HM, Hız SA, Çarman KB, Dündar NO, Okuyaz Ç, Aydın K, Serdaroğlu A, Tekgül H, Cansu A
Epilepsy Res 2022 Aug;184:106963. Epub 2022 Jun 6 doi: 10.1016/j.eplepsyres.2022.106963. PMID: 35749975
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
Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD, Schorge S, Baez-Nieto D, Wang HR, Allen A, Pan JQ, Lerche H, Heyne H, Symonds JD, Zuberi SM, Sanders S, Sheidley BR, Craiu D, Olson HE, Weckhuysen S, DeJonge P, Helbig I, Van Esch H, Busa T, Milh M, Isidor B, Depienne C, Poduri A, Campbell AJ, Dimidschstein J, Møller RS, Lal D
Epilepsia 2020 Mar;61(3):387-399. Epub 2020 Feb 23 doi: 10.1111/epi.16438. PMID: 32090326

Prognosis

Giacomini T, Nuovo S, Zanni G, Mancardi MM, Cusmai R, Pepi C, Bertini E, Valente EM, Battini R, Ferrari A, Romaniello R, Zucca C, Borgatti R, Uccella S, Severino M, Striano P, Pistorio A, Prato G, De Grandis E, Nobili L, Pisciotta L
Eur J Paediatr Neurol 2021 Mar;31:61-69. Epub 2021 Feb 19 doi: 10.1016/j.ejpn.2021.02.006. PMID: 33640666
Matricardi S, De Liso P, Freri E, Costa P, Castellotti B, Magri S, Gellera C, Granata T, Musante L, Lesca G, Oertel J, Craiu D, Hammer TB, Møller RS, Barisic N, Abou Jamra R, Polster T, Vigevano F, Marini C
Epilepsia 2020 Nov;61(11):2474-2485. Epub 2020 Oct 16 doi: 10.1111/epi.16699. PMID: 33063863
Bar C, Kuchenbuch M, Barcia G, Schneider A, Jennesson M, Le Guyader G, Lesca G, Mignot C, Montomoli M, Parrini E, Isnard H, Rolland A, Keren B, Afenjar A, Dorison N, Sadleir LG, Breuillard D, Levy R, Rio M, Dupont S, Negrin S, Danieli A, Scalais E, De Saint Martin A, El Chehadeh S, Chelly J, Poisson A, Lebre AS, Nica A, Odent S, Sekhara T, Brankovic V, Goldenberg A, Vrielynck P, Lederer D, Maurey H, Terrone G, Besmond C, Hubert L, Berquin P, Billette de Villemeur T, Isidor B, Freeman JL, Mefford HC, Myers CT, Howell KB, Rodríguez-Sacristán Cascajo A, Meyer P, Genevieve D, Guët A, Doummar D, Durigneux J, van Dooren MF, de Wit MCY, Gerard M, Marey I, Munnich A, Guerrini R, Scheffer IE, Kabashi E, Nabbout R
Epilepsia 2020 Nov;61(11):2461-2473. Epub 2020 Sep 21 doi: 10.1111/epi.16679. PMID: 32954514
Bayat A, Knaus A, Pendziwiat M, Afenjar A, Barakat TS, Bosch F, Callewaert B, Calvas P, Ceulemans B, Chassaing N, Depienne C, Endziniene M, Ferreira CR, Moura de Souza CF, Freihuber C, Ganesan S, Gataullina S, Guerrini R, Guerrot AM, Hansen L, Jezela-Stanek A, Karsenty C, Kievit A, Kooy FR, Korff CM, Kragh Hansen J, Larsen M, Layet V, Lesca G, McBride KL, Meuwissen M, Mignot C, Montomoli M, Moore H, Naudion S, Nava C, Nougues MC, Parrini E, Pastore M, Schelhaas JH, Skinner S, Szczałuba K, Thomas A, Thomassen M, Tranebjaerg L, van Slegtenhorst M, Wolfe LA, Lal D, Gardella E, Bomme Ousager L, Brünger T, Helbig I, Krawitz P, Møller RS
Epilepsia 2020 Jun;61(6):1142-1155. Epub 2020 May 26 doi: 10.1111/epi.16545. PMID: 32452540
Harini C, Nagarajan E, Bergin AM, Pearl P, Loddenkemper T, Takeoka M, Morrison PF, Coulter D, Harappanahally G, Marti C, Singh K, Yuskaitis C, Poduri A, Libenson MH
Epilepsia 2020 Apr;61(4):702-713. Epub 2020 Mar 5 doi: 10.1111/epi.16468. PMID: 32133641

Clinical prediction guides

Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free 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
Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD, Schorge S, Baez-Nieto D, Wang HR, Allen A, Pan JQ, Lerche H, Heyne H, Symonds JD, Zuberi SM, Sanders S, Sheidley BR, Craiu D, Olson HE, Weckhuysen S, DeJonge P, Helbig I, Van Esch H, Busa T, Milh M, Isidor B, Depienne C, Poduri A, Campbell AJ, Dimidschstein J, Møller RS, Lal D
Epilepsia 2020 Mar;61(3):387-399. Epub 2020 Feb 23 doi: 10.1111/epi.16438. PMID: 32090326
Takata A, Nakashima M, Saitsu H, Mizuguchi T, Mitsuhashi S, Takahashi Y, Okamoto N, Osaka H, Nakamura K, Tohyama J, Haginoya K, Takeshita S, Kuki I, Okanishi T, Goto T, Sasaki M, Sakai Y, Miyake N, Miyatake S, Tsuchida N, Iwama K, Minase G, Sekiguchi F, Fujita A, Imagawa E, Koshimizu E, Uchiyama Y, Hamanaka K, Ohba C, Itai T, Aoi H, Saida K, Sakaguchi T, Den K, Takahashi R, Ikeda H, Yamaguchi T, Tsukamoto K, Yoshitomi S, Oboshi T, Imai K, Kimizu T, Kobayashi Y, Kubota M, Kashii H, Baba S, Iai M, Kira R, Hara M, Ohta M, Miyata Y, Miyata R, Takanashi JI, Matsui J, Yokochi K, Shimono M, Amamoto M, Takayama R, Hirabayashi S, Aiba K, Matsumoto H, Nabatame S, Shiihara T, Kato M, Matsumoto N
Nat Commun 2019 Jun 7;10(1):2506. doi: 10.1038/s41467-019-10482-9. PMID: 31175295Free PMC Article
Inokuchi JI, Go S, Yoshikawa M, Strauss K
Biochim Biophys Acta Gen Subj 2017 Oct;1861(10):2485-2493. Epub 2017 May 30 doi: 10.1016/j.bbagen.2017.05.025. PMID: 28571946

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
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
Sharawat IK, Panda PK, Kasinathan A, Panda P, Dawman L, Joshi K
Seizure 2021 Feb;85:119-126. Epub 2021 Jan 11 doi: 10.1016/j.seizure.2020.12.016. PMID: 33461030
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
Hon JM, Bhattacharya JJ, Counsell CE, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Al-Shahi Salman R; SIVMS Collaborators
Stroke 2009 Jun;40(6):1980-5. Epub 2009 Apr 23 doi: 10.1161/STROKEAHA.108.533034. PMID: 19390075

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