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Developmental and epileptic encephalopathy 104(DEE104)

MedGen UID:
1823956
Concept ID:
C5774183
Disease or Syndrome
Synonym: DEE104
 
Gene (location): ATP6V0A1 (17q21.2)
 
Monarch Initiative: MONDO:0031021
OMIM®: 619970

Definition

Developmental and epileptic encephalopathy-104 (DEE104) is an autosomal dominant disorder characterized by developmental delay in the first few months of life and drug-resistant focal and generalized tonic-clonic seizures (summary by Bott et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
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.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Agitation
MedGen UID:
88447
Concept ID:
C0085631
Sign or Symptom
A state of extreme restlessness and excessive motor activity is associated with mental distress or a feeling of inner tension.
Clonic seizure
MedGen UID:
66708
Concept ID:
C0234535
Disease or Syndrome
A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive.
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.
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.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
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.
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.
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.
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
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 roll over
MedGen UID:
1718874
Concept ID:
C5397980
Finding
Delayed achievement of the ability to roll front to back and back to front.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Professional guidelines

PubMed

Falsaperla R, Criscione R, Cimino C, Pisani F, Ruggieri M
Neuropediatrics 2023 Oct;54(5):297-307. Epub 2023 Mar 22 doi: 10.1055/a-2060-4576. PMID: 36948217
Kolc KL, Sadleir LG, Depienne C, Marini C, Scheffer IE, Møller RS, Trivisano M, Specchio N, Pham D, Kumar R, Roberts R, Gecz J
Transl Psychiatry 2020 May 4;10(1):127. doi: 10.1038/s41398-020-0803-0. PMID: 32366910Free PMC Article
Horinek D, Cihar M, Tichy M
Bratisl Lek Listy 2003;104(11):347-51. PMID: 15055719

Recent clinical studies

Etiology

Cavirani B, Spagnoli C, Caraffi SG, Cavalli A, Cesaroni CA, Cutillo G, De Giorgis V, Frattini D, Marchetti GB, Masnada S, Peron A, Rizzi S, Varesio C, Spaccini L, Vignoli A, Canevini MP, Veggiotti P, Garavelli L, Fusco C
Int J Mol Sci 2024 Jan 19;25(2) doi: 10.3390/ijms25021248. PMID: 38279250Free PMC Article
Falsaperla R, Criscione R, Cimino C, Pisani F, Ruggieri M
Neuropediatrics 2023 Oct;54(5):297-307. Epub 2023 Mar 22 doi: 10.1055/a-2060-4576. PMID: 36948217
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article
Salpietro V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S, Torti E, Hacke M, Rankin J, Tariq H, Colin E, Procaccio V, Striano P, Mankad K, Lieb A, Chen S, Pisani L, Bettencourt C, Männikkö R, Manole A, Brusco A, Grosso E, Ferrero GB, Armstrong-Moron J, Gueden S, Bar-Yosef O, Tzadok M, Monaghan KG, Santiago-Sim T, Person RE, Cho MT, Willaert R, Yoo Y, Chae JH, Quan Y, Wu H, Wang T, Bernier RA, Xia K, Blesson A, Jain M, Motazacker MM, Jaeger B, Schneider AL, Boysen K, Muir AM, Myers CT, Gavrilova RH, Gunderson L, Schultz-Rogers L, Klee EW, Dyment D, Osmond M, Parellada M, Llorente C, Gonzalez-Peñas J, Carracedo A, Van Haeringen A, Ruivenkamp C, Nava C, Heron D, Nardello R, Iacomino M, Minetti C, Skabar A, Fabretto A; SYNAPS Study Group, Raspall-Chaure M, Chez M, Tsai A, Fassi E, Shinawi M, Constantino JN, De Zorzi R, Fortuna S, Kok F, Keren B, Bonneau D, Choi M, Benzeev B, Zara F, Mefford HC, Scheffer IE, Clayton-Smith J, Macaya A, Rothman JE, Eichler EE, Kullmann DM, Houlden H
Nat Commun 2019 Jul 12;10(1):3094. doi: 10.1038/s41467-019-10910-w. PMID: 31300657Free PMC Article
O'Donnell-Luria AH, Pais LS, Faundes V, Wood JC, Sveden A, Luria V, Abou Jamra R, Accogli A, Amburgey K, Anderlid BM, Azzarello-Burri S, Basinger AA, Bianchini C, Bird LM, Buchert R, Carre W, Ceulemans S, Charles P, Cox H, Culliton L, Currò A; Deciphering Developmental Disorders (DDD) Study, Demurger F, Dowling JJ, Duban-Bedu B, Dubourg C, Eiset SE, Escobar LF, Ferrarini A, Haack TB, Hashim M, Heide S, Helbig KL, Helbig I, Heredia R, Héron D, Isidor B, Jonasson AR, Joset P, Keren B, Kok F, Kroes HY, Lavillaureix A, Lu X, Maas SM, Maegawa GHB, Marcelis CLM, Mark PR, Masruha MR, McLaughlin HM, McWalter K, Melchinger EU, Mercimek-Andrews S, Nava C, Pendziwiat M, Person R, Ramelli GP, Ramos LLP, Rauch A, Reavey C, Renieri A, Rieß A, Sanchez-Valle A, Sattar S, Saunders C, Schwarz N, Smol T, Srour M, Steindl K, Syrbe S, Taylor JC, Telegrafi A, Thiffault I, Trauner DA, van der Linden H Jr, van Koningsbruggen S, Villard L, Vogel I, Vogt J, Weber YG, Wentzensen IM, Widjaja E, Zak J, Baxter S, Banka S, Rodan LH
Am J Hum Genet 2019 Jun 6;104(6):1210-1222. Epub 2019 May 9 doi: 10.1016/j.ajhg.2019.03.021. PMID: 31079897Free PMC Article

Diagnosis

Cavirani B, Spagnoli C, Caraffi SG, Cavalli A, Cesaroni CA, Cutillo G, De Giorgis V, Frattini D, Marchetti GB, Masnada S, Peron A, Rizzi S, Varesio C, Spaccini L, Vignoli A, Canevini MP, Veggiotti P, Garavelli L, Fusco C
Int J Mol Sci 2024 Jan 19;25(2) doi: 10.3390/ijms25021248. PMID: 38279250Free PMC Article
Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Hu C, Liu D, Luo T, Wang Y, Liu Z
Epileptic Disord 2022 Apr 1;24(2):343-352. doi: 10.1684/epd.2021.1394. PMID: 34859793
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article
Helbig I, Lopez-Hernandez T, Shor O, Galer P, Ganesan S, Pendziwiat M, Rademacher A, Ellis CA, Hümpfer N, Schwarz N, Seiffert S, Peeden J, Shen J, Štěrbová K, Hammer TB, Møller RS, Shinde DN, Tang S, Smith L, Poduri A, Krause R, Benninger F, Helbig KL, Haucke V, Weber YG; EuroEPINOMICS-RES Consortium; GRIN Consortium
Am J Hum Genet 2019 Jun 6;104(6):1060-1072. Epub 2019 May 16 doi: 10.1016/j.ajhg.2019.04.001. PMID: 31104773Free PMC Article

Therapy

Thomas SV, Jeemon P, Jose M, Amrithum LM, Bhaskar D, Nair MKC, George B
Epileptic Disord 2022 Jun 1;24(3):531-540. doi: 10.1684/epd.2022.1414. PMID: 35770752
Winterhalder R, McCabe J, Young C, Lamb K, Sawhney I, Jory C, O'Dwyer M, Shankar R
Acta Neurol Scand 2022 Jun;145(6):753-761. Epub 2022 Mar 17 doi: 10.1111/ane.13612. PMID: 35297524Free PMC Article
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article
Vasquez A, Gaínza-Lein M, Abend NS, Amengual-Gual M, Anderson A, Arya R, Brenton JN, Carpenter JL, Chapman K, Clark J, Farias-Moeller R, Gaillard WD, Glauser T, Goldstein JL, Goodkin HP, Guerriero RM, Kapur K, Lai YC, McDonough TL, Mikati MA, Morgan LA, Novotny EJ, Ostendorf AP, Payne ET, Peariso K, Piantino J, Riviello JJ, Sannagowdara K, Tasker RC, Tchapyjnikov D, Topjian A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; Pediatric Status Epilepticus Research Group (pSERG)
Neurology 2020 Nov 10;95(19):e2683-e2696. Epub 2020 Sep 10 doi: 10.1212/WNL.0000000000010828. PMID: 32913024Free PMC Article
Vendrame M, Guilhoto LM, Loddenkemper T, Gregas M, Bourgeois BF, Kothare SV
Pediatr Neurol 2012 May;46(5):276-80. doi: 10.1016/j.pediatrneurol.2012.02.022. PMID: 22520347

Prognosis

Riant F, Burglen L, Corpechot M, Robert J, Durr A, Solé G, Petit F, Freihuber C, De Marco O, Sarret C, Castelnovo G, Devillard F, Afenjar A, Héron B, Lasserve ET
Clin Genet 2023 Sep;104(3):365-370. Epub 2023 May 13 doi: 10.1111/cge.14358. PMID: 37177896
Rossi A, Blok LS, Neuser S, Klöckner C, Platzer K, Faivre LO, Weigand H, Dentici ML, Tartaglia M, Niceta M, Alfieri P, Srivastava S, Coulter D, Smith L, Vinorum K, Cappuccio G, Brunetti-Pierri N, Torun D, Arslan M, Lauridsen MF, Murch O, Irving R, Lynch SA, Mehta SG, Carmichael J, Zonneveld-Huijssoon E, de Vries B, Kleefstra T, Johannesen KM, Westphall IT, Hughes SS, Smithson S, Evans J, Dudding-Byth T, Simon M, van Binsbergen E, Herkert JC, Beunders G, Oppermann H, Bakal M, Møller RS, Rubboli G, Bayat A
Clin Genet 2023 Aug;104(2):186-197. Epub 2023 May 10 doi: 10.1111/cge.14353. PMID: 37165752Free PMC Article
Mo A, Paz-Ebstein E, Yanovsky-Dagan S, Lai A, Mor-Shaked H, Gilboa T, Yang E, Shao DD, Walsh CA, Harel T
Clin Genet 2023 Jul;104(1):73-80. Epub 2023 Apr 2 doi: 10.1111/cge.14335. PMID: 37005340Free PMC Article
Schon KR, Horvath R, Wei W, Calabrese C, Tucci A, Ibañez K, Ratnaike T, Pitceathly RDS, Bugiardini E, Quinlivan R, Hanna MG, Clement E, Ashton E, Sayer JA, Brennan P, Josifova D, Izatt L, Fratter C, Nesbitt V, Barrett T, McMullen DJ, Smith A, Deshpande C, Smithson SF, Festenstein R, Canham N, Caulfield M, Houlden H, Rahman S, Chinnery PF; Genomics England Research Consortium
BMJ 2021 Nov 3;375:e066288. doi: 10.1136/bmj-2021-066288. PMID: 34732400Free PMC Article
Gorman KM, Meyer E, Grozeva D, Spinelli E, McTague A, Sanchis-Juan A, Carss KJ, Bryant E, Reich A, Schneider AL, Pressler RM, Simpson MA, Debelle GD, Wassmer E, Morton J, Sieciechowicz D, Jan-Kamsteeg E, Paciorkowski AR, King MD, Cross JH, Poduri A, Mefford HC, Scheffer IE, Haack TB, McCullagh G; Deciphering Developmental Disorders Study; UK10K Consortium; NIHR BioResource, Millichap JJ, Carvill GL, Clayton-Smith J, Maher ER, Raymond FL, Kurian MA
Am J Hum Genet 2019 May 2;104(5):948-956. Epub 2019 Apr 11 doi: 10.1016/j.ajhg.2019.03.005. PMID: 30982612Free PMC Article

Clinical prediction guides

Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Rossi A, Blok LS, Neuser S, Klöckner C, Platzer K, Faivre LO, Weigand H, Dentici ML, Tartaglia M, Niceta M, Alfieri P, Srivastava S, Coulter D, Smith L, Vinorum K, Cappuccio G, Brunetti-Pierri N, Torun D, Arslan M, Lauridsen MF, Murch O, Irving R, Lynch SA, Mehta SG, Carmichael J, Zonneveld-Huijssoon E, de Vries B, Kleefstra T, Johannesen KM, Westphall IT, Hughes SS, Smithson S, Evans J, Dudding-Byth T, Simon M, van Binsbergen E, Herkert JC, Beunders G, Oppermann H, Bakal M, Møller RS, Rubboli G, Bayat A
Clin Genet 2023 Aug;104(2):186-197. Epub 2023 May 10 doi: 10.1111/cge.14353. PMID: 37165752Free PMC Article
Mo A, Paz-Ebstein E, Yanovsky-Dagan S, Lai A, Mor-Shaked H, Gilboa T, Yang E, Shao DD, Walsh CA, Harel T
Clin Genet 2023 Jul;104(1):73-80. Epub 2023 Apr 2 doi: 10.1111/cge.14335. PMID: 37005340Free PMC Article
Kolc KL, Sadleir LG, Depienne C, Marini C, Scheffer IE, Møller RS, Trivisano M, Specchio N, Pham D, Kumar R, Roberts R, Gecz J
Transl Psychiatry 2020 May 4;10(1):127. doi: 10.1038/s41398-020-0803-0. PMID: 32366910Free PMC Article
Gorman KM, Meyer E, Grozeva D, Spinelli E, McTague A, Sanchis-Juan A, Carss KJ, Bryant E, Reich A, Schneider AL, Pressler RM, Simpson MA, Debelle GD, Wassmer E, Morton J, Sieciechowicz D, Jan-Kamsteeg E, Paciorkowski AR, King MD, Cross JH, Poduri A, Mefford HC, Scheffer IE, Haack TB, McCullagh G; Deciphering Developmental Disorders Study; UK10K Consortium; NIHR BioResource, Millichap JJ, Carvill GL, Clayton-Smith J, Maher ER, Raymond FL, Kurian MA
Am J Hum Genet 2019 May 2;104(5):948-956. Epub 2019 Apr 11 doi: 10.1016/j.ajhg.2019.03.005. PMID: 30982612Free PMC Article

Recent systematic reviews

Falsaperla R, Criscione R, Cimino C, Pisani F, Ruggieri M
Neuropediatrics 2023 Oct;54(5):297-307. Epub 2023 Mar 22 doi: 10.1055/a-2060-4576. PMID: 36948217
Della Vecchia S, Lopergolo D, Trovato R, Pasquariello R, Ferrari AR, Bartolini E
Seizure 2023 Jan;104:32-37. Epub 2022 Nov 29 doi: 10.1016/j.seizure.2022.11.014. PMID: 36476360

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