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Epileptic encephalopathy, infantile or early childhood, 3(DEE93)

MedGen UID:
1642888
Concept ID:
C4693934
Disease or Syndrome
Synonym: DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 93
 
Gene (location): ATP6V1A (3q13.31)
 
Monarch Initiative: MONDO:0020632
OMIM®: 618012

Definition

Developmental and epileptic encephalopathy (DEE93) is an autosomal dominant neurologic disorder characterized by delayed psychomotor development, early-onset refractory seizures, and impaired intellectual development. The severity of the phenotype is highly variable: some patients may be nonverbal and nonambulatory with spastic quadriparesis and poor eye contact, whereas others have moderate intellectual disability (summary by Fassio et al., 2018). For 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 characterised 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.
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.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
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.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
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.
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
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.
Iris coloboma
MedGen UID:
116097
Concept ID:
C0240063
Anatomical Abnormality
A coloboma of the iris.

Professional guidelines

PubMed

Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
Katyayan A, Diaz-Medina G
Neurol Clin 2021 Aug;39(3):779-795. doi: 10.1016/j.ncl.2021.04.002. PMID: 34215386
Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, Yanovski JA
J Clin Endocrinol Metab 2017 Mar 1;102(3):709-757. doi: 10.1210/jc.2016-2573. PMID: 28359099Free PMC Article

Recent clinical studies

Etiology

Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
Wirrell EC, Hood V, Knupp KG, Meskis MA, Nabbout R, Scheffer IE, Wilmshurst J, Sullivan J
Epilepsia 2022 Jul;63(7):1761-1777. Epub 2022 May 12 doi: 10.1111/epi.17274. PMID: 35490361Free PMC Article
Reynolds C, King MD, Gorman KM
Eur J Paediatr Neurol 2020 Jan;24:117-122. Epub 2019 Dec 12 doi: 10.1016/j.ejpn.2019.12.016. PMID: 31924505
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
Epi4K Consortium; Epilepsy Phenome/Genome Project, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR
Nature 2013 Sep 12;501(7466):217-21. Epub 2013 Aug 11 doi: 10.1038/nature12439. PMID: 23934111Free PMC Article

Diagnosis

Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
Wirrell EC, Hood V, Knupp KG, Meskis MA, Nabbout R, Scheffer IE, Wilmshurst J, Sullivan J
Epilepsia 2022 Jul;63(7):1761-1777. Epub 2022 May 12 doi: 10.1111/epi.17274. PMID: 35490361Free PMC Article
Leonard H, Downs J, Benke TA, Swanson L, Olson H, Demarest S
Lancet Neurol 2022 Jun;21(6):563-576. Epub 2022 Apr 25 doi: 10.1016/S1474-4422(22)00035-7. PMID: 35483386Free PMC Article
Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Katyayan A, Diaz-Medina G
Neurol Clin 2021 Aug;39(3):779-795. doi: 10.1016/j.ncl.2021.04.002. PMID: 34215386

Therapy

Elkommos S, Mula M
Expert Opin Pharmacother 2022 Dec;23(18):2023-2034. Epub 2022 Sep 27 doi: 10.1080/14656566.2022.2128670. PMID: 36154780
Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
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
Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, Katz R, Di Marzo V, Jutras-Aswad D, Notcutt WG, Martinez-Orgado J, Robson PJ, Rohrback BG, Thiele E, Whalley B, Friedman D
Epilepsia 2014 Jun;55(6):791-802. Epub 2014 May 22 doi: 10.1111/epi.12631. PMID: 24854329Free PMC Article
Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D
Epileptic Disord 2007 Dec;9(4):353-412. doi: 10.1684/epd.2007.0144. PMID: 18077226

Prognosis

Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, Pressler R, Auvin S, Samia P, Hirsch E, Galicchio S, Triki C, Snead OC, Wiebe S, Cross JH, Tinuper P, Scheffer IE, Perucca E, Moshé SL, Nabbout R
Epilepsia 2022 Jun;63(6):1349-1397. Epub 2022 May 3 doi: 10.1111/epi.17239. PMID: 35503712
Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Katyayan A, Diaz-Medina G
Neurol Clin 2021 Aug;39(3):779-795. doi: 10.1016/j.ncl.2021.04.002. PMID: 34215386
Pavone P, Polizzi A, Marino SD, Corsello G, Falsaperla R, Marino S, Ruggieri M
Neurol Sci 2020 Dec;41(12):3547-3562. Epub 2020 Aug 22 doi: 10.1007/s10072-020-04600-5. PMID: 32827285Free PMC Article
Reynolds C, King MD, Gorman KM
Eur J Paediatr Neurol 2020 Jan;24:117-122. Epub 2019 Dec 12 doi: 10.1016/j.ejpn.2019.12.016. PMID: 31924505

Clinical prediction guides

Riikonen R
Pediatr Neurol 2020 Jul;108:54-64. Epub 2020 Feb 4 doi: 10.1016/j.pediatrneurol.2020.01.015. PMID: 32305143
Reynolds C, King MD, Gorman KM
Eur J Paediatr Neurol 2020 Jan;24:117-122. Epub 2019 Dec 12 doi: 10.1016/j.ejpn.2019.12.016. PMID: 31924505
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
Epi4K Consortium; Epilepsy Phenome/Genome Project, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR
Nature 2013 Sep 12;501(7466):217-21. Epub 2013 Aug 11 doi: 10.1038/nature12439. PMID: 23934111Free PMC Article
Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D
Epileptic Disord 2007 Dec;9(4):353-412. doi: 10.1684/epd.2007.0144. PMID: 18077226

Recent systematic reviews

Soares RC, da Rosa SV, Moysés ST, Rocha JS, Bettega PVC, Werneck RI, Moysés SJ
Int J Paediatr Dent 2021 May;31(3):394-421. Epub 2021 Feb 17 doi: 10.1111/ipd.12766. PMID: 33263186
Solmi M, Radua J, Stubbs B, Ricca V, Moretti D, Busatta D, Carvalho AF, Dragioti E, Favaro A, Monteleone AM, Shin JI, Fusar-Poli P, Castellini G
Braz J Psychiatry 2021 May-Jun;43(3):314-323. doi: 10.1590/1516-4446-2020-1099. PMID: 32997075Free PMC Article
LeMoult J, Humphreys KL, Tracy A, Hoffmeister JA, Ip E, Gotlib IH
J Am Acad Child Adolesc Psychiatry 2020 Jul;59(7):842-855. Epub 2019 Oct 30 doi: 10.1016/j.jaac.2019.10.011. PMID: 31676392
Xiao J, Alkhers N, Kopycka-Kedzierawski DT, Billings RJ, Wu TT, Castillo DA, Rasubala L, Malmstrom H, Ren Y, Eliav E
Caries Res 2019;53(4):411-421. Epub 2019 Jan 10 doi: 10.1159/000495187. PMID: 30630167Free PMC Article
Contreras V, Toro MJ, Elías-Boneta AR, Encarnación-Burgos A
Gen Dent 2017 May-Jun;65(3):22-29. PMID: 28475081Free PMC Article

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