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Developmental and epileptic encephalopathy 99(DEE99)

MedGen UID:
1794228
Concept ID:
C5562018
Disease or Syndrome
Synonyms: DEE99; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 99
 
Gene (location): ATP1A3 (19q13.2)
 
Monarch Initiative: MONDO:0030473
OMIM®: 619606

Definition

Developmental and epileptic encephalopathy-99 (DEE99) is characterized by onset of seizures in early childhood associated with global developmental delay and severely impaired intellectual development. Other features may include hypotonia, quadriparesis, nystagmus, and apnea. Brain imaging may be normal or show nonspecific and variable abnormalities, including cerebral atrophy and polymicrogyria. The severity is variable; some patients die of refractory status epilepticus (summary by Vetro et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
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.
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.
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.
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.
Eyelid myoclonus
MedGen UID:
148288
Concept ID:
C0751349
Disease or Syndrome
Marked, involuntary jerking of the eyelids.
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.
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
Thick corpus callosum
MedGen UID:
371993
Concept ID:
C1835194
Finding
Increased vertical dimension of the corpus callosum. This feature can be visualized by sagittal sections on magnetic resonance tomography imaging of the brain.
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.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Perisylvian polymicrogyria
MedGen UID:
481305
Concept ID:
C3279675
Finding
Polymicrogyria (an excessive number of small gyri or convolutions) that is maximal in perisylvian regions (the regions that surround the Sylvian fissures), which may be symmetric or asymmetric and may extend beyond perisylvian regions. The Sylvian fissures often extend posteriorly and superiorly.
Multifocal seizures
MedGen UID:
482664
Concept ID:
C3281034
Finding
Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations).
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.
Multifocal epileptiform discharges
MedGen UID:
866864
Concept ID:
C4021219
Finding
An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci).
Frontotemporal cerebral atrophy
MedGen UID:
867226
Concept ID:
C4021584
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the frontotemporal cerebrum.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Atrophy/Degeneration affecting the brainstem
MedGen UID:
870454
Concept ID:
C4024900
Disease or Syndrome
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.
Hypoplastic hippocampus
MedGen UID:
1388294
Concept ID:
C4476822
Congenital Abnormality
Underdevelopment of the hippocampus.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.
Central apnea
MedGen UID:
854403
Concept ID:
C3887548
Disease or Syndrome
Apnea resulting from depression of the respiratory centers in the medulla oblongata. There is a lack of respiratory effort rather than obstruction of airflow.
High-pitched cry
MedGen UID:
116082
Concept ID:
C0239154
Finding
A type of crying in an abnormally high-pitched voice.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Exodeviation
MedGen UID:
1637525
Concept ID:
C4551670
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate temporally.

Professional guidelines

PubMed

MacKay CI, Wong K, Demarest ST, Benke TA, Downs J, Leonard H
Clin Genet 2021 Jan;99(1):157-165. Epub 2020 Oct 20 doi: 10.1111/cge.13862. PMID: 33047306
Kim HJ, Yang D, Kim SH, Kim B, Kim HD, Lee JS, Choi JR, Lee ST, Kang HC
Epileptic Disord 2020 Oct 1;22(5):563-570. doi: 10.1684/epd.2020.1199. PMID: 33000761
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article

Recent clinical studies

Etiology

Sanders MW, Van der Wolf I, Jansen FE, Aronica E, Helmstaedter C, Racz A, Surges R, Grote A, Becker AJ, Rheims S, Catenoix H, Duncan JS, De Tisi J, Jacques TS, Cross JH, Kalviainen R, Rauramaa T, Chassoux F, Devaux BC, Di Gennaro G, Esposito V, Bodi I, Honavar M, Bien CG, Cloppenborg T, Coras R, Hamer HM, Marusic P, Kalina A, Pieper T, Kudernatsch M, Hartlieb TS, Von Oertzen TJ, Aichholzer M, Dorfmuller G, Chipaux M, Noachtar S, Kaufmann E, Schulze-Bonhage A, Scheiwe CF, Özkara C, Grunwald T, Koenig K, Guerrini R, Barba C, Buccoliero AM, Giordano F, Rosenow F, Menzler K, Garbelli R, Deleo F, Krsek P, Straka B, Arzimanoglou AA, Toulouse J, Van Paesschen W, Theys T, Pimentel J, Loução De Amorim IM, Specchio N, De Palma L, Feucht M, Scholl T, Roessler K, Toledano Delgado R, Gil-Nagel A, Raicevic S, Ristic AJ, Schijns O, Beckervordersandforth J, San Antonio-Arce V, Rumia J, Blumcke I, Braun KP; as the European Epilepsy Brain Bank Consortium (EEBB)
Neurology 2024 Feb 27;102(4):e208007. Epub 2024 Jan 30 doi: 10.1212/WNL.0000000000208007. PMID: 38290094Free PMC Article
Kim SH, Seo J, Kwon SS, Teng LY, Won D, Shin S, Lee JS, Lee ST, Choi JR, Kang HC
Epilepsia 2024 Mar;65(3):766-778. Epub 2023 Dec 22 doi: 10.1111/epi.17857. PMID: 38073125
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
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP; United Kingdom Infantile Spasms Study
Lancet Neurol 2005 Nov;4(11):712-7. doi: 10.1016/S1474-4422(05)70199-X. PMID: 16239177

Diagnosis

Kim SH, Seo J, Kwon SS, Teng LY, Won D, Shin S, Lee JS, Lee ST, Choi JR, Kang HC
Epilepsia 2024 Mar;65(3):766-778. Epub 2023 Dec 22 doi: 10.1111/epi.17857. PMID: 38073125
Macdonald-Laurs E, Warren AEL, Francis P, Mandelstam SA, Lee WS, Coleman M, Stephenson SEM, Barton S, D'Arcy C, Lockhart PJ, Leventer RJ, Harvey AS
Brain 2024 Apr 4;147(4):1264-1277. doi: 10.1093/brain/awad379. PMID: 37939785
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
Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Fry AE, Németh AH, Tofaris GK, Hay E, Hughes I, Mansour S, Mordekar SR, Splitt M, Turnpenny PD, Demetriou D, Koopmann TT, Ruivenkamp CAL, Agrawal PB, Carr L, Clowes V, Ghali N, Holder SE, Radley J, Male A, Sisodiya SM, Kurian MA, Cross JH, Balasubramanian M
Neurology 2022 Oct 4;99(14):e1511-e1526. Epub 2022 Jul 18 doi: 10.1212/WNL.0000000000200927. PMID: 36192182Free PMC Article
Sauro KM, Wiebe S, Dunkley C, Janszky J, Kumlien E, Moshé S, Nakasato N, Pedley TA, Perucca E, Senties H, Thomas SV, Wang Y, Wilmshurst J, Jetté N
Epilepsia 2016 Jan;57(1):13-23. Epub 2015 Dec 10 doi: 10.1111/epi.13273. PMID: 26659723

Therapy

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
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
Patel AD, Mazurkiewicz-Bełdzińska M, Chin RF, Gil-Nagel A, Gunning B, Halford JJ, Mitchell W, Scott Perry M, Thiele EA, Weinstock A, Dunayevich E, Checketts D, Devinsky O
Epilepsia 2021 Sep;62(9):2228-2239. Epub 2021 Jul 20 doi: 10.1111/epi.17000. PMID: 34287833
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP; United Kingdom Infantile Spasms Study
Lancet Neurol 2005 Nov;4(11):712-7. doi: 10.1016/S1474-4422(05)70199-X. PMID: 16239177

Prognosis

GBD 2021 Stroke Risk Factor Collaborators
Lancet Neurol 2024 Oct;23(10):973-1003. doi: 10.1016/S1474-4422(24)00369-7. PMID: 39304265
Macdonald-Laurs E, Warren AEL, Francis P, Mandelstam SA, Lee WS, Coleman M, Stephenson SEM, Barton S, D'Arcy C, Lockhart PJ, Leventer RJ, Harvey AS
Brain 2024 Apr 4;147(4):1264-1277. doi: 10.1093/brain/awad379. PMID: 37939785
Jethwa S, Pressler RM, Kaya D, Datta AN
Eur J Paediatr Neurol 2022 Nov;41:99-108. Epub 2022 Nov 11 doi: 10.1016/j.ejpn.2022.11.004. PMID: 36410286
Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Dalla Bernardina B, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffler M, Lerche H, Lesca G, Lewis-Smith D, Marini C, Marjanovic D, Mazzola L, McKeown Ruggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S
Neurology 2022 Jul 19;99(3):e221-e233. Epub 2022 Jun 3 doi: 10.1212/WNL.0000000000200715. PMID: 35851549Free PMC Article
Kim HJ, Yang D, Kim SH, Kim B, Kim HD, Lee JS, Choi JR, Lee ST, Kang HC
Epileptic Disord 2020 Oct 1;22(5):563-570. doi: 10.1684/epd.2020.1199. PMID: 33000761

Clinical prediction guides

Vezyroglou A, Akilapa R, Barwick K, Koene S, Brownstein CA, Holder-Espinasse M, Fry AE, Németh AH, Tofaris GK, Hay E, Hughes I, Mansour S, Mordekar SR, Splitt M, Turnpenny PD, Demetriou D, Koopmann TT, Ruivenkamp CAL, Agrawal PB, Carr L, Clowes V, Ghali N, Holder SE, Radley J, Male A, Sisodiya SM, Kurian MA, Cross JH, Balasubramanian M
Neurology 2022 Oct 4;99(14):e1511-e1526. Epub 2022 Jul 18 doi: 10.1212/WNL.0000000000200927. PMID: 36192182Free PMC Article
Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, Chiesa V, Christensen J, Dalla Bernardina B, Ellis CA, Furia F, Gardiner F, Giron C, Guerrini R, Klein KM, Korff C, Krijtova H, Leffler M, Lerche H, Lesca G, Lewis-Smith D, Marini C, Marjanovic D, Mazzola L, McKeown Ruggiero S, Mochel F, Ramond F, Reif PS, Richard-Mornas A, Rosenow F, Schropp C, Thomas RH, Vignoli A, Weber Y, Palmer E, Helbig I, Scheffer IE, Striano P, Møller RS, Gardella E, Weckhuysen S
Neurology 2022 Jul 19;99(3):e221-e233. Epub 2022 Jun 3 doi: 10.1212/WNL.0000000000200715. PMID: 35851549Free PMC Article
Patel AD, Mazurkiewicz-Bełdzińska M, Chin RF, Gil-Nagel A, Gunning B, Halford JJ, Mitchell W, Scott Perry M, Thiele EA, Weinstock A, Dunayevich E, Checketts D, Devinsky O
Epilepsia 2021 Sep;62(9):2228-2239. Epub 2021 Jul 20 doi: 10.1111/epi.17000. PMID: 34287833
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP; United Kingdom Infantile Spasms Study
Lancet Neurol 2005 Nov;4(11):712-7. doi: 10.1016/S1474-4422(05)70199-X. PMID: 16239177

Recent systematic reviews

Pisano S, Melis M, Figorilli M, Polizzi L, Rocchi L, Giglio S, Defazio G, Muroni A
Seizure 2022 Jul;99:12-15. Epub 2022 Apr 18 doi: 10.1016/j.seizure.2022.04.010. PMID: 35525099
Chang X, Wu Y, Zhou J, Meng H, Zhang W, Guo J
Medicine (Baltimore) 2020 Jan;99(5):e18634. doi: 10.1097/MD.0000000000018634. PMID: 32000367Free PMC Article
McTague A, Martland T, Appleton R
Cochrane Database Syst Rev 2018 Jan 10;1(1):CD001905. doi: 10.1002/14651858.CD001905.pub3. PMID: 29320603Free PMC Article
Sauro KM, Wiebe S, Dunkley C, Janszky J, Kumlien E, Moshé S, Nakasato N, Pedley TA, Perucca E, Senties H, Thomas SV, Wang Y, Wilmshurst J, Jetté N
Epilepsia 2016 Jan;57(1):13-23. Epub 2015 Dec 10 doi: 10.1111/epi.13273. PMID: 26659723
Banach R, Boskovic R, Einarson T, Koren G
Drug Saf 2010 Jan 1;33(1):73-9. doi: 10.2165/11317640-000000000-00000. PMID: 20000869

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