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Developmental and epileptic encephalopathy, 86(EIEE86; DEE86)

MedGen UID:
1711964
Concept ID:
C5394462
Disease or Syndrome
Synonym: EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 86
 
Gene (location): DALRD3 (3p21.31)
 
Monarch Initiative: MONDO:0030054
OMIM®: 618910

Definition

Developmental and epileptic encephalopathy-86 (DEE86) is an X-linked neurologic syndrome characterized by severe and persistent seizures associated with EEG abnormalities beginning in the first few months of life, global developmental delay, severe motor deficits, dystonic movements, and dysmorphic facial features (Lentini et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Gastrostomy tube feeding in infancy
MedGen UID:
892362
Concept ID:
C4023342
Finding
Feeding problem necessitating gastrostomy tube feeding.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.

Professional guidelines

PubMed

Bayat A, Fenger CD, Techlo TR, Højte AF, Nørgaard I, Hansen TF, Rubboli G, Møller RS, Group DCCRS
Neurotherapeutics 2022 Jul;19(4):1353-1367. Epub 2022 Jun 20 doi: 10.1007/s13311-022-01264-1. PMID: 35723786Free PMC Article
Rus CM, Weissensteiner T, Pereira C, Susnea I, Danquah BD, Morales Torres G, Rocha ME, Cozma C, Saravanakumar D, Mannepalli S, Kandaswamy KK, Di Bucchianico S, Zimmermann R, Rolfs A, Bauer P, Beetz C
Orphanet J Rare Dis 2022 May 3;17(1):179. doi: 10.1186/s13023-022-02288-8. PMID: 35505348Free PMC Article
Platzer K, Yuan H, Schütz H, Winschel A, Chen W, Hu C, Kusumoto H, Heyne HO, Helbig KL, Tang S, Willing MC, Tinkle BT, Adams DJ, Depienne C, Keren B, Mignot C, Frengen E, Strømme P, Biskup S, Döcker D, Strom TM, Mefford HC, Myers CT, Muir AM, LaCroix A, Sadleir L, Scheffer IE, Brilstra E, van Haelst MM, van der Smagt JJ, Bok LA, Møller RS, Jensen UB, Millichap JJ, Berg AT, Goldberg EM, De Bie I, Fox S, Major P, Jones JR, Zackai EH, Abou Jamra R, Rolfs A, Leventer RJ, Lawson JA, Roscioli T, Jansen FE, Ranza E, Korff CM, Lehesjoki AE, Courage C, Linnankivi T, Smith DR, Stanley C, Mintz M, McKnight D, Decker A, Tan WH, Tarnopolsky MA, Brady LI, Wolff M, Dondit L, Pedro HF, Parisotto SE, Jones KL, Patel AD, Franz DN, Vanzo R, Marco E, Ranells JD, Di Donato N, Dobyns WB, Laube B, Traynelis SF, Lemke JR
J Med Genet 2017 Jul;54(7):460-470. Epub 2017 Apr 4 doi: 10.1136/jmedgenet-2016-104509. PMID: 28377535Free PMC Article

Recent clinical studies

Etiology

Soldovieri MV, Ambrosino P, Mosca I, Servettini I, Pietrunti F, Belperio G; KCNA3 study group, Syrbe S, Taglialatela M, Lemke JR
Ann Neurol 2024 Feb;95(2):365-376. Epub 2023 Dec 28 doi: 10.1002/ana.26826. PMID: 37964487
Knight EMP, Amin S, Bahi-Buisson N, Benke TA, Cross JH, Demarest ST, Olson HE, Specchio N, Fleming TR, Aimetti AA, Gasior M, Devinsky O; Marigold Trial Group
Lancet Neurol 2022 May;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1. PMID: 35429480
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
Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium, Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE
Ann Neurol 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. PMID: 31618474Free 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

Diagnosis

Beck VC, Isom LL, Berg AT
J Pediatr 2021 Oct;237:41-49.e1. Epub 2021 Jun 26 doi: 10.1016/j.jpeds.2021.06.034. PMID: 34181986Free PMC Article
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
Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium, Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE
Ann Neurol 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. PMID: 31618474Free PMC Article
Saletti PG, Ali I, Casillas-Espinosa PM, Semple BD, Lisgaras CP, Moshé SL, Galanopoulou AS
Neurobiol Dis 2019 Mar;123:86-99. Epub 2018 Jun 22 doi: 10.1016/j.nbd.2018.06.017. PMID: 29936231Free PMC Article
Platzer K, Yuan H, Schütz H, Winschel A, Chen W, Hu C, Kusumoto H, Heyne HO, Helbig KL, Tang S, Willing MC, Tinkle BT, Adams DJ, Depienne C, Keren B, Mignot C, Frengen E, Strømme P, Biskup S, Döcker D, Strom TM, Mefford HC, Myers CT, Muir AM, LaCroix A, Sadleir L, Scheffer IE, Brilstra E, van Haelst MM, van der Smagt JJ, Bok LA, Møller RS, Jensen UB, Millichap JJ, Berg AT, Goldberg EM, De Bie I, Fox S, Major P, Jones JR, Zackai EH, Abou Jamra R, Rolfs A, Leventer RJ, Lawson JA, Roscioli T, Jansen FE, Ranza E, Korff CM, Lehesjoki AE, Courage C, Linnankivi T, Smith DR, Stanley C, Mintz M, McKnight D, Decker A, Tan WH, Tarnopolsky MA, Brady LI, Wolff M, Dondit L, Pedro HF, Parisotto SE, Jones KL, Patel AD, Franz DN, Vanzo R, Marco E, Ranells JD, Di Donato N, Dobyns WB, Laube B, Traynelis SF, Lemke JR
J Med Genet 2017 Jul;54(7):460-470. Epub 2017 Apr 4 doi: 10.1136/jmedgenet-2016-104509. PMID: 28377535Free PMC Article

Therapy

Knight EMP, Amin S, Bahi-Buisson N, Benke TA, Cross JH, Demarest ST, Olson HE, Specchio N, Fleming TR, Aimetti AA, Gasior M, Devinsky O; Marigold Trial Group
Lancet Neurol 2022 May;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1. PMID: 35429480
Saletti PG, Ali I, Casillas-Espinosa PM, Semple BD, Lisgaras CP, Moshé SL, Galanopoulou AS
Neurobiol Dis 2019 Mar;123:86-99. Epub 2018 Jun 22 doi: 10.1016/j.nbd.2018.06.017. PMID: 29936231Free PMC Article
Huber-Mollema Y, van Iterson L, Sander JW, Oort FJ, Lindhout D, Rodenburg R
Epilepsy Behav 2018 Sep;86:187-192. Epub 2018 Jul 17 doi: 10.1016/j.yebeh.2018.06.043. PMID: 30030084
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
Platzer K, Yuan H, Schütz H, Winschel A, Chen W, Hu C, Kusumoto H, Heyne HO, Helbig KL, Tang S, Willing MC, Tinkle BT, Adams DJ, Depienne C, Keren B, Mignot C, Frengen E, Strømme P, Biskup S, Döcker D, Strom TM, Mefford HC, Myers CT, Muir AM, LaCroix A, Sadleir L, Scheffer IE, Brilstra E, van Haelst MM, van der Smagt JJ, Bok LA, Møller RS, Jensen UB, Millichap JJ, Berg AT, Goldberg EM, De Bie I, Fox S, Major P, Jones JR, Zackai EH, Abou Jamra R, Rolfs A, Leventer RJ, Lawson JA, Roscioli T, Jansen FE, Ranza E, Korff CM, Lehesjoki AE, Courage C, Linnankivi T, Smith DR, Stanley C, Mintz M, McKnight D, Decker A, Tan WH, Tarnopolsky MA, Brady LI, Wolff M, Dondit L, Pedro HF, Parisotto SE, Jones KL, Patel AD, Franz DN, Vanzo R, Marco E, Ranells JD, Di Donato N, Dobyns WB, Laube B, Traynelis SF, Lemke JR
J Med Genet 2017 Jul;54(7):460-470. Epub 2017 Apr 4 doi: 10.1136/jmedgenet-2016-104509. PMID: 28377535Free PMC Article

Prognosis

Li J, Ji Z, Yu J, Ren J, Yang F, Bian L, Zhi X, Li G, Zhang H
Stroke Vasc Neurol 2023 Aug;8(4):292-300. Epub 2023 Jan 6 doi: 10.1136/svn-2022-001979. PMID: 36609545Free PMC Article
Yang S, Yang LM, Liao HM, Fang HJ, Ning ZS, Liao CS, Wu LW
Neurol Sci 2022 Aug;43(8):5039-5048. Epub 2022 Mar 29 doi: 10.1007/s10072-022-06038-3. PMID: 35352205
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
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
Kadish NE, Riedel C, Stephani U, Wiegand G
Epilepsy Behav 2020 Oct;111:107182. Epub 2020 Jun 11 doi: 10.1016/j.yebeh.2020.107182. PMID: 32535369

Clinical prediction guides

Soldovieri MV, Ambrosino P, Mosca I, Servettini I, Pietrunti F, Belperio G; KCNA3 study group, Syrbe S, Taglialatela M, Lemke JR
Ann Neurol 2024 Feb;95(2):365-376. Epub 2023 Dec 28 doi: 10.1002/ana.26826. PMID: 37964487
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
Elgendy MM, Puthuraya S, LoPiccolo C, Liu W, Aly H, Karnati S
Pediatr Neonatol 2022 Jan;63(1):41-47. Epub 2021 Aug 28 doi: 10.1016/j.pedneo.2021.06.017. PMID: 34509386
Masnada S, Pichiecchio A, Formica M, Arrigoni F, Borrelli P, Accorsi P, Bonanni P, Borgatti R, Bernardina BD, Danieli A, Darra F, Deconinck N, De Giorgis V, Dulac O, Gataullina S, Giordano L, Guerrini R, La Briola F, Mastrangelo M, Montomoli M, Mortilla M, Osanni E, Parisi P, Perucca E, Pinelli L, Romaniello R, Severino M, Vigevano F, Vignoli A, Bahi-Buisson N, Cavallin M, Accogli A, Burgeois M, Capra V, Chaves-Vischer V, Chiapparini L, Colafati G, D'Arrigo S, Desguerre I, Doco-Fenzy M, d'Orsi G, Epitashvili N, Fazzi E, Ferretti A, Fiorini E, Fradin M, Fusco C, Granata T, Johannesen KM, Lebon S, Loget P, Moller RS, Montanaro D, Orcesi S, Quelin C, Rebessi E, Romeo A, Solazzi R, Spagnoli C, Uebler C, Zara F, Arzimanoglou A, Veggiotti P; Aicardi Syndrome International Study Group
Neurology 2021 Mar 2;96(9):e1319-e1333. Epub 2020 Dec 4 doi: 10.1212/WNL.0000000000011237. PMID: 33277420Free PMC Article
Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium, Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE
Ann Neurol 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. PMID: 31618474Free PMC Article

Recent systematic reviews

Yates CF, Malone S, Riney K, Shah U, Wood MJ
Pediatr Neurosurg 2023;58(1):18-28. Epub 2023 Jan 13 doi: 10.1159/000529098. PMID: 36693334Free PMC Article
Chakravarty K, Ray S, Kharbanda PS, Lal V, Baishya J
Acta Neurol Scand 2021 Sep;144(3):236-250. Epub 2021 May 13 doi: 10.1111/ane.13455. PMID: 33987835
Dunbar MJ, Woodward K, Leijser LM, Kirton A
Dev Med Child Neurol 2021 Feb;63(2):144-155. Epub 2020 Oct 22 doi: 10.1111/dmcn.14713. PMID: 33094492
Jansson JS, Hallböök T, Reilly C
Epilepsy Behav 2020 Jul;108:107079. Epub 2020 Apr 22 doi: 10.1016/j.yebeh.2020.107079. PMID: 32334365

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