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Developmental and epileptic encephalopathy 112(DEE112)

MedGen UID:
1845523
Concept ID:
C5882700
Disease or Syndrome
Synonyms: DEE112; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 112
 
Gene (location): KCNH5 (14q23.2)
 
Monarch Initiative: MONDO:0957812
OMIM®: 620537

Definition

Developmental and epileptic encephalopathy-112 (DEE112) is an autosomal dominant disorder characterized by a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes range from normal intellect to profound impairment (summary by Happ et al., 2023). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Focal motor seizure
MedGen UID:
5237
Concept ID:
C0016399
Disease or Syndrome
A type of focal-onset seizure characterized by a motor sign as its initial semiological manifestation.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
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.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
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.
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.
Chiari type I malformation
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line)
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Focal tonic seizure
MedGen UID:
199867
Concept ID:
C0752324
Disease or Syndrome
A type of focal motor seizure characterized by sustained increase in muscle contraction, lasting a few seconds to minutes.
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.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Focal hemiclonic seizure
MedGen UID:
335477
Concept ID:
C1846620
Disease or Syndrome
A type of focal clonic seizure characterized by sustained rhythmic jerking rapidly involves one side of the body at seizure onset.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
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).
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
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.
Focal aware motor seizure
MedGen UID:
1719715
Concept ID:
C5397594
Disease or Syndrome
A type of focal motor seizure in which awareness is retained throughout the seizure.
Focal impaired awareness motor seizure
MedGen UID:
1710565
Concept ID:
C5397722
Disease or Syndrome
A type of focal motor seizure in which awareness is partially or fully impaired at some point during the seizure.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.

Professional guidelines

PubMed

Dai W, Sun Y, Fan Y, Gao Y, Zhan Y, Wang L, Xiao B, Qiu W, Gu X, Sun K, Yu Y, Xu N
Eur J Hum Genet 2023 Jan;31(1):112-121. Epub 2022 Nov 14 doi: 10.1038/s41431-022-01217-4. PMID: 36376392Free PMC Article
Herzberg EM, Machie M, Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, Cilio MR, Bonifacio SL, Massey SL, McCulloch CE, Soul JS; Neonatal Seizure Registry study group
J Pediatr 2022 Mar;242:121-128.e1. Epub 2021 Nov 13 doi: 10.1016/j.jpeds.2021.11.012. PMID: 34780777
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403

Recent clinical studies

Etiology

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
Poke G, Stanley J, Scheffer IE, Sadleir LG
Neurology 2023 Mar 28;100(13):e1363-e1375. Epub 2022 Dec 29 doi: 10.1212/WNL.0000000000206758. PMID: 36581463Free PMC Article
Bailey LD, Schwartz L, Dixon-Salazar T, Meskis MA, Galer BS, Gammaitoni AR, Schad C
Epilepsy Behav 2020 Nov;112:107377. Epub 2020 Aug 22 doi: 10.1016/j.yebeh.2020.107377. PMID: 32846306
Veroniki AA, Rios P, Cogo E, Straus SE, Finkelstein Y, Kealey R, Reynen E, Soobiah C, Thavorn K, Hutton B, Hemmelgarn BR, Yazdi F, D'Souza J, MacDonald H, Tricco AC
BMJ Open 2017 Jul 20;7(7):e017248. doi: 10.1136/bmjopen-2017-017248. PMID: 28729328Free PMC Article
Aaberg KM, Gunnes N, Bakken IJ, Lund Søraas C, Berntsen A, Magnus P, Lossius MI, Stoltenberg C, Chin R, Surén P
Pediatrics 2017 May;139(5) Epub 2017 Apr 5 doi: 10.1542/peds.2016-3908. PMID: 28557750

Diagnosis

Terada K, Kubota Y, Dimova S, Elmoufti S, Floricel F, Chellun D, O'Brien TJ
Seizure 2023 Nov;112:62-67. Epub 2023 Sep 13 doi: 10.1016/j.seizure.2023.09.011. PMID: 37769545
Poke G, Stanley J, Scheffer IE, Sadleir LG
Neurology 2023 Mar 28;100(13):e1363-e1375. Epub 2022 Dec 29 doi: 10.1212/WNL.0000000000206758. PMID: 36581463Free PMC Article
Herzberg EM, Machie M, Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, Cilio MR, Bonifacio SL, Massey SL, McCulloch CE, Soul JS; Neonatal Seizure Registry study group
J Pediatr 2022 Mar;242:121-128.e1. Epub 2021 Nov 13 doi: 10.1016/j.jpeds.2021.11.012. PMID: 34780777
Dal Canto G, Pellacani S, Valvo G, Masi G, Ferrari AR, Sicca F
Epilepsy Behav 2018 Feb;79:68-74. Epub 2017 Dec 15 doi: 10.1016/j.yebeh.2017.10.004. PMID: 29253677
Aaberg KM, Gunnes N, Bakken IJ, Lund Søraas C, Berntsen A, Magnus P, Lossius MI, Stoltenberg C, Chin R, Surén P
Pediatrics 2017 May;139(5) Epub 2017 Apr 5 doi: 10.1542/peds.2016-3908. PMID: 28557750

Therapy

Gil-Nagel A, Cross JH, Devinsky O, Ceulemans B, Lagae L, Knupp K, Schoonjans AS, Ryvlin P, Thiele EA, Polega S, Lothe A, Nabbout R
Epilepsia 2024 Aug;65(8):2186-2199. Epub 2024 Jun 21 doi: 10.1111/epi.18020. PMID: 39030735
Terada K, Kubota Y, Dimova S, Elmoufti S, Floricel F, Chellun D, O'Brien TJ
Seizure 2023 Nov;112:62-67. Epub 2023 Sep 13 doi: 10.1016/j.seizure.2023.09.011. PMID: 37769545
Coughlin CR, Tseng LA, Bok LA, Hartmann H, Footitt E, Striano P, Tabarki BM, Lunsing RJ, Stockler-Ipsiroglu S, Gordon S, Van Hove JLK, Abdenur JE, Boyer M, Longo N, Andrews A, Janssen MCH, van Wegberg A, Prasad C, Prasad AN, Lamb MM, Wijburg FA, Gospe SM Jr, van Karnebeek C; International PDE Consortium
Neurology 2022 Dec 5;99(23):e2627-e2636. doi: 10.1212/WNL.0000000000201222. PMID: 36008148Free PMC Article
Aaberg KM, Bakken IJ, Lossius MI, Lund Søraas C, Tallur KK, Stoltenberg C, Chin R, Surén P
Pediatrics 2018 Jun;141(6) Epub 2018 May 22 doi: 10.1542/peds.2017-4016. PMID: 29789444
Veroniki AA, Rios P, Cogo E, Straus SE, Finkelstein Y, Kealey R, Reynen E, Soobiah C, Thavorn K, Hutton B, Hemmelgarn BR, Yazdi F, D'Souza J, MacDonald H, Tricco AC
BMJ Open 2017 Jul 20;7(7):e017248. doi: 10.1136/bmjopen-2017-017248. PMID: 28729328Free PMC Article

Prognosis

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
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
Aaberg KM, Bakken IJ, Lossius MI, Lund Søraas C, Tallur KK, Stoltenberg C, Chin R, Surén P
Pediatrics 2018 Jun;141(6) Epub 2018 May 22 doi: 10.1542/peds.2017-4016. PMID: 29789444
Peng J, Wang Y, He F, Chen C, Wu LW, Yang LF, Ma YP, Zhang W, Shi ZQ, Chen C, Xia K, Guo H, Yin F, Pang N
CNS Neurosci Ther 2018 Dec;24(12):1196-1206. Epub 2018 Apr 17 doi: 10.1111/cns.12860. PMID: 29667327Free PMC Article
Aaberg KM, Gunnes N, Bakken IJ, Lund Søraas C, Berntsen A, Magnus P, Lossius MI, Stoltenberg C, Chin R, Surén P
Pediatrics 2017 May;139(5) Epub 2017 Apr 5 doi: 10.1542/peds.2016-3908. PMID: 28557750

Clinical prediction guides

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
Coughlin CR, Tseng LA, Bok LA, Hartmann H, Footitt E, Striano P, Tabarki BM, Lunsing RJ, Stockler-Ipsiroglu S, Gordon S, Van Hove JLK, Abdenur JE, Boyer M, Longo N, Andrews A, Janssen MCH, van Wegberg A, Prasad C, Prasad AN, Lamb MM, Wijburg FA, Gospe SM Jr, van Karnebeek C; International PDE Consortium
Neurology 2022 Dec 5;99(23):e2627-e2636. doi: 10.1212/WNL.0000000000201222. PMID: 36008148Free PMC Article
Lewis H, Samanta D, Örsell JL, Bosanko KA, Rowell A, Jones M, Dale RC, Taravath S, Hahn CD, Krishnakumar D, Chagnon S, Keller S, Hagebeuk E, Pathak S, Bebin EM, Arndt DH, Alexander JJ, Mainali G, Coppola G, Maclean J, Sparagana S, McNamara N, Smith DM, Raggio V, Cruz M, Fernández-Jaén A, Kava MP, Emrick L, Fish JL, Vanderver A, Helman G, Pierson TM, Zarate YA
Pediatr Neurol 2020 Nov;112:94-100. Epub 2020 Apr 13 doi: 10.1016/j.pediatrneurol.2020.04.006. PMID: 32446642Free PMC Article
Peng J, Wang Y, He F, Chen C, Wu LW, Yang LF, Ma YP, Zhang W, Shi ZQ, Chen C, Xia K, Guo H, Yin F, Pang N
CNS Neurosci Ther 2018 Dec;24(12):1196-1206. Epub 2018 Apr 17 doi: 10.1111/cns.12860. PMID: 29667327Free PMC Article
Aaberg KM, Gunnes N, Bakken IJ, Lund Søraas C, Berntsen A, Magnus P, Lossius MI, Stoltenberg C, Chin R, Surén P
Pediatrics 2017 May;139(5) Epub 2017 Apr 5 doi: 10.1542/peds.2016-3908. PMID: 28557750

Recent systematic reviews

Gil-Nagel A, Cross JH, Devinsky O, Ceulemans B, Lagae L, Knupp K, Schoonjans AS, Ryvlin P, Thiele EA, Polega S, Lothe A, Nabbout R
Epilepsia 2024 Aug;65(8):2186-2199. Epub 2024 Jun 21 doi: 10.1111/epi.18020. PMID: 39030735
Veroniki AA, Rios P, Cogo E, Straus SE, Finkelstein Y, Kealey R, Reynen E, Soobiah C, Thavorn K, Hutton B, Hemmelgarn BR, Yazdi F, D'Souza J, MacDonald H, Tricco AC
BMJ Open 2017 Jul 20;7(7):e017248. doi: 10.1136/bmjopen-2017-017248. PMID: 28729328Free PMC Article
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
Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD
Mol Genet Metab 2014 Aug;112(4):259-74. Epub 2014 May 29 doi: 10.1016/j.ymgme.2014.05.011. PMID: 24953403

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