Format

Send to:

Choose Destination

Early infantile epileptic encephalopathy 14(DEE14)

MedGen UID:
767109
Concept ID:
C3554195
Disease or Syndrome
Synonyms: DEE14; DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 14
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): KCNT1 (9q34.3)
 
Monarch Initiative: MONDO:0013989
OMIM®: 614959

Disease characteristics

Excerpted from the GeneReview: KCNT1-Related Epilepsy
KCNT1-related epilepsy is most often associated with two phenotypes: epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). EIMFS is characterized by seizures, typically focal and asynchronous, beginning in the first six months of life with associated developmental plateau or regression. Autonomic manifestations (e.g., perioral cyanosis, flushing, apnea) are common. Seizures are intractable to multiple anticonvulsants and progress to become nearly continuous by age six to nine months. ADNFLE is characterized by clusters of nocturnal motor seizures that vary from simple arousals to hyperkinetic events with tonic or dystonic features. Individuals with KCNT1-related ADNFLE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems than individuals with ADNFLE due to other causes. Less common seizure phenotypes in individuals with KCNT1-related epilepsy include West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, leukodystrophy and/or leukoencephalopathy, focal epilepsy, and multifocal epilepsy. Additional neurologic features include hypotonia, microcephaly developing by age 12 months, strabismus, profound developmental delay, and additional movement disorders. Other systemic manifestations including pulmonary hemorrhage caused by prominent systemic-to-pulmonary collateral arteries or cardiac arrhythmia have been reported. [from GeneReviews]
Authors:
Tracy Gertler  |  David Bearden  |  Arin Bhattacharjee, et. al.   view full author information

Additional descriptions

From OMIM
Developmental and epileptic encephalopathy-14 (DEE14) is a severe neurologic disorder characterized by onset in the first 6 months of life of refractory focal seizures and arrest of psychomotor development. Ictal EEG shows discharges that arise randomly from various areas of both hemispheres and migrate from one brain region to another. The disorder presents as 'malignant migrating partial seizures of infancy' (MMPSI), a clinical designation (summary by Barcia et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.  http://www.omim.org/entry/614959
From MedlinePlus Genetics
Malignant migrating partial seizures of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures begin before the age of 6 months but commonly start within a few weeks of birth. The seizures do not respond well to treatment. Although affected individuals may develop normally at first, progression stalls and skills decline when seizures begin; as a result, affected individuals have profound developmental delay.\n\nThe seizures in MMPSI are described as partial (or focal) because the seizure activity occurs in regions of the brain rather than affecting the entire brain. Seizure activity can appear in multiple locations in the brain or move (migrate) from one region to another during an episode. Depending on the region affected, seizures can involve sudden redness and warmth (flushing) of the face; drooling; short pauses in breathing (apnea); movement of the head or eyes to one side; twitches in the eyelids or tongue; chewing motions; or jerking of an arm, leg, or both on one side of the body. If seizure activity spreads to affect the entire brain, it causes a loss of consciousness, muscle stiffening, and rhythmic jerking (tonic-clonic seizure). Episodes that begin as partial seizures and spread throughout the brain are known as secondarily generalized seizures.\n\nInitially, the seizures associated with MMPSI are relatively infrequent, occurring every few weeks. Within a few months of the seizures starting, though, the frequency increases. Affected individuals can have clusters of five to 30 seizures several times a day. Each seizure typically lasts seconds to a couple of minutes, but they can be prolonged (classified as status epilepticus). In some cases, the seizure activity may be almost continuous for several days. After a year or more of persistent seizures, the episodes become less frequent.\n\nSeizures can affect growth of the brain and lead to a small head size (microcephaly). The problems with brain development can also cause profound developmental delay and intellectual impairment. Affected babies often lose the mental and motor skills they developed after birth, such as the ability to make eye contact and control their head movement. Many have weak muscle tone (hypotonia) and become "floppy." If seizures can be controlled for a short period, development may improve. Some affected children learn to reach for objects or walk. However, most children with this condition do not develop language skills.\n\nBecause of the serious health problems caused by MMPSI, many affected individuals do not survive past infancy or early childhood.  https://medlineplus.gov/genetics/condition/malignant-migrating-partial-seizures-of-infancy

Clinical features

From HPO
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Tetraplegia
MedGen UID:
19617
Concept ID:
C0034372
Disease or Syndrome
Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
A life-threatening situation in which the brain is in a continuous state of seizure.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
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.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Poor eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
Difficulty in looking at another person in the eye.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Recent clinical studies

Etiology

Howell KB, Freeman JL, Mackay MT, Fahey MC, Archer J, Berkovic SF, Chan E, Dabscheck G, Eggers S, Hayman M, Holberton J, Hunt RW, Jacobs SE, Kornberg AJ, Leventer RJ, Mandelstam S, McMahon JM, Mefford HC, Panetta J, Riseley J, Rodriguez-Casero V, Ryan MM, Schneider AL, Smith LJ, Stark Z, Wong F, Yiu EM, Scheffer IE, Harvey AS
Epilepsia 2021 Feb;62(2):358-370. Epub 2021 Jan 21 doi: 10.1111/epi.16810. PMID: 33475165
Galer PD, Ganesan S, Lewis-Smith D, McKeown SE, Pendziwiat M, Helbig KL, Ellis CA, Rademacher A, Smith L, Poduri A, Seiffert S, von Spiczak S, Muhle H, van Baalen A; NCEE Study Group.; EPGP Investigators.; EuroEPINOMICS-RES Consortium.; Genomics Research and Innovation Network., Thomas RH, Krause R, Weber Y, Helbig I
Am J Hum Genet 2020 Oct 1;107(4):683-697. Epub 2020 Aug 26 doi: 10.1016/j.ajhg.2020.08.003. PMID: 32853554Free PMC Article
Hirabayashi K, Uehara DT, Abe H, Ishii A, Moriyama K, Hirose S, Inazawa J
J Hum Genet 2019 Nov;64(11):1097-1106. Epub 2019 Aug 30 doi: 10.1038/s10038-019-0661-x. PMID: 31471553
Radaelli G, de Souza Santos F, Borelli WV, Pisani L, Nunes ML, Scorza FA, da Costa JC
Epilepsy Behav 2018 Aug;85:32-36. Epub 2018 Jun 13 doi: 10.1016/j.yebeh.2018.05.015. PMID: 29906699
Vrielynck P, Marique P, Ghariani S, Lienard F, de Borchgrave V, van Rijckevorsel K, Bonnier C
Eur J Paediatr Neurol 2017 Mar;21(2):305-311. Epub 2016 Sep 8 doi: 10.1016/j.ejpn.2016.08.015. PMID: 27641809

Diagnosis

Yang H, Gong P, Jiao X, Zhou Q, Zhang Y, Jiang Y, Yang Z
Sci Rep 2021 Aug 5;11(1):15903. doi: 10.1038/s41598-021-95040-4. PMID: 34354098Free PMC Article
Howell KB, Freeman JL, Mackay MT, Fahey MC, Archer J, Berkovic SF, Chan E, Dabscheck G, Eggers S, Hayman M, Holberton J, Hunt RW, Jacobs SE, Kornberg AJ, Leventer RJ, Mandelstam S, McMahon JM, Mefford HC, Panetta J, Riseley J, Rodriguez-Casero V, Ryan MM, Schneider AL, Smith LJ, Stark Z, Wong F, Yiu EM, Scheffer IE, Harvey AS
Epilepsia 2021 Feb;62(2):358-370. Epub 2021 Jan 21 doi: 10.1111/epi.16810. PMID: 33475165
Matsumoto H, Zaha K, Nakamura Y, Hayashi S, Inazawa J, Nonoyama S
Pediatr Neurol 2014 Jul;51(1):170-5. Epub 2014 Apr 4 doi: 10.1016/j.pediatrneurol.2014.03.013. PMID: 24938147
Campbell IM, Yatsenko SA, Hixson P, Reimschisel T, Thomas M, Wilson W, Dayal U, Wheless JW, Crunk A, Curry C, Parkinson N, Fishman L, Riviello JJ, Nowaczyk MJ, Zeesman S, Rosenfeld JA, Bejjani BA, Shaffer LG, Cheung SW, Lupski JR, Stankiewicz P, Scaglia F
Genet Med 2012 Oct;14(10):868-76. Epub 2012 Jun 21 doi: 10.1038/gim.2012.65. PMID: 22722545Free PMC Article
Saitsu H, Kato M, Okada I, Orii KE, Higuchi T, Hoshino H, Kubota M, Arai H, Tagawa T, Kimura S, Sudo A, Miyama S, Takami Y, Watanabe T, Nishimura A, Nishiyama K, Miyake N, Wada T, Osaka H, Kondo N, Hayasaka K, Matsumoto N
Epilepsia 2010 Dec;51(12):2397-405. Epub 2010 Sep 30 doi: 10.1111/j.1528-1167.2010.02728.x. PMID: 20887364

Therapy

Howell KB, Freeman JL, Mackay MT, Fahey MC, Archer J, Berkovic SF, Chan E, Dabscheck G, Eggers S, Hayman M, Holberton J, Hunt RW, Jacobs SE, Kornberg AJ, Leventer RJ, Mandelstam S, McMahon JM, Mefford HC, Panetta J, Riseley J, Rodriguez-Casero V, Ryan MM, Schneider AL, Smith LJ, Stark Z, Wong F, Yiu EM, Scheffer IE, Harvey AS
Epilepsia 2021 Feb;62(2):358-370. Epub 2021 Jan 21 doi: 10.1111/epi.16810. PMID: 33475165
Radaelli G, de Souza Santos F, Borelli WV, Pisani L, Nunes ML, Scorza FA, da Costa JC
Epilepsy Behav 2018 Aug;85:32-36. Epub 2018 Jun 13 doi: 10.1016/j.yebeh.2018.05.015. PMID: 29906699
Vrielynck P, Marique P, Ghariani S, Lienard F, de Borchgrave V, van Rijckevorsel K, Bonnier C
Eur J Paediatr Neurol 2017 Mar;21(2):305-311. Epub 2016 Sep 8 doi: 10.1016/j.ejpn.2016.08.015. PMID: 27641809
Korff CM, Vulliemoz S, Picard F, Fluss J
Eur J Paediatr Neurol 2012 Nov;16(6):753-7. Epub 2012 Jul 4 doi: 10.1016/j.ejpn.2012.05.009. PMID: 22766350

Prognosis

Howell KB, Freeman JL, Mackay MT, Fahey MC, Archer J, Berkovic SF, Chan E, Dabscheck G, Eggers S, Hayman M, Holberton J, Hunt RW, Jacobs SE, Kornberg AJ, Leventer RJ, Mandelstam S, McMahon JM, Mefford HC, Panetta J, Riseley J, Rodriguez-Casero V, Ryan MM, Schneider AL, Smith LJ, Stark Z, Wong F, Yiu EM, Scheffer IE, Harvey AS
Epilepsia 2021 Feb;62(2):358-370. Epub 2021 Jan 21 doi: 10.1111/epi.16810. PMID: 33475165
Radaelli G, de Souza Santos F, Borelli WV, Pisani L, Nunes ML, Scorza FA, da Costa JC
Epilepsy Behav 2018 Aug;85:32-36. Epub 2018 Jun 13 doi: 10.1016/j.yebeh.2018.05.015. PMID: 29906699
Giorgio E, Vaula G, Bosco G, Giacone S, Mancini C, Calcia A, Cavalieri S, Di Gregorio E, Rigault De Longrais R, Leombruni S, Pinessi L, Cerrato P, Brusco A, Brussino A
J Neurol Sci 2015 May 15;352(1-2):99-104. Epub 2015 Apr 7 doi: 10.1016/j.jns.2015.03.042. PMID: 25873210
Korff CM, Vulliemoz S, Picard F, Fluss J
Eur J Paediatr Neurol 2012 Nov;16(6):753-7. Epub 2012 Jul 4 doi: 10.1016/j.ejpn.2012.05.009. PMID: 22766350
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E
Brain Dev 1987;9(4):371-6. doi: 10.1016/s0387-7604(87)80110-9. PMID: 3434712

Clinical prediction guides

Galer PD, Ganesan S, Lewis-Smith D, McKeown SE, Pendziwiat M, Helbig KL, Ellis CA, Rademacher A, Smith L, Poduri A, Seiffert S, von Spiczak S, Muhle H, van Baalen A; NCEE Study Group.; EPGP Investigators.; EuroEPINOMICS-RES Consortium.; Genomics Research and Innovation Network., Thomas RH, Krause R, Weber Y, Helbig I
Am J Hum Genet 2020 Oct 1;107(4):683-697. Epub 2020 Aug 26 doi: 10.1016/j.ajhg.2020.08.003. PMID: 32853554Free PMC Article
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
Giorgio E, Vaula G, Bosco G, Giacone S, Mancini C, Calcia A, Cavalieri S, Di Gregorio E, Rigault De Longrais R, Leombruni S, Pinessi L, Cerrato P, Brusco A, Brussino A
J Neurol Sci 2015 May 15;352(1-2):99-104. Epub 2015 Apr 7 doi: 10.1016/j.jns.2015.03.042. PMID: 25873210
Horita H
Psychiatry Clin Neurosci 2001 Jun;55(3):171-2. doi: 10.1046/j.1440-1819.2001.00812.x. PMID: 11422828
Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E
Brain Dev 1987;9(4):371-6. doi: 10.1016/s0387-7604(87)80110-9. PMID: 3434712

Recent systematic reviews

Radaelli G, de Souza Santos F, Borelli WV, Pisani L, Nunes ML, Scorza FA, da Costa JC
Epilepsy Behav 2018 Aug;85:32-36. Epub 2018 Jun 13 doi: 10.1016/j.yebeh.2018.05.015. PMID: 29906699

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center