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Developmental and epileptic encephalopathy, 83(EIEE83; DEE83)

MedGen UID:
1684784
Concept ID:
C5231487
Disease or Syndrome
Synonyms: BARAKAT-PERENTHALER SYNDROME; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 83
 
Gene (location): UGP2 (2p15)
 
Monarch Initiative: MONDO:0032895
OMIM®: 618744

Definition

Developmental and epileptic encephalopathy-83 (DEE83) is a severe autosomal recessive neurodevelopmental disorder characterized by onset of frequent seizures in the first days to months of life that are usually refractory to medical treatment and are associated with significant EEG abnormalities. Affected individuals have profoundly impaired development, with no motor or language skill acquisition, poor or absent visual tracking, and poor oromotor function necessitating tube feeding. Many patients die in the first years of life (summary by Perenthaler et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
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.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Tetraparesis
MedGen UID:
78731
Concept ID:
C0270790
Finding
Weakness of all four limbs.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Persistent head lag
MedGen UID:
256151
Concept ID:
C1141883
Finding
The Premie-Neuro and the Dubowitz Neurological Examination score head lag in the same manner. Scoring for both is as follows
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
High anterior hairline
MedGen UID:
477667
Concept ID:
C3276036
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Foveal hypoplasia
MedGen UID:
393047
Concept ID:
C2673946
Finding
Underdevelopment of the fovea centralis.

Professional guidelines

PubMed

Edey J, Soleimani-Nouri P, Dawson-Kavanagh A, Imran Azeem MS, Episkopou V
Int J Dev Neurosci 2023 Nov;83(7):581-599. Epub 2023 Aug 13 doi: 10.1002/jdn.10290. PMID: 37574439
Du X, Wang J, Li S, Ma Y, Wang T, Wu B, Zhou Y, Yu L, Wang Y
Genes (Basel) 2022 Aug 14;13(8) doi: 10.3390/genes13081447. PMID: 36011358Free PMC Article
Lee S, Karp N, Zapata-Aldana E, Sadikovic B, Yang P, Balci TB, Prasad AN
Can J Neurol Sci 2021 Mar;48(2):233-244. Epub 2020 Aug 3 doi: 10.1017/cjn.2020.167. PMID: 32741404

Recent clinical studies

Etiology

Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free 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
Nappi P, Miceli F, Soldovieri MV, Ambrosino P, Barrese V, Taglialatela M
Pflugers Arch 2020 Jul;472(7):881-898. Epub 2020 Jun 6 doi: 10.1007/s00424-020-02404-2. PMID: 32506321
O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP; participating investigators
Lancet Neurol 2017 Jan;16(1):33-42. Epub 2016 Nov 10 doi: 10.1016/S1474-4422(16)30294-0. PMID: 27838190
Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, Löscher W
Acta Neuropathol 2016 Feb;131(2):211-234. Epub 2015 Sep 30 doi: 10.1007/s00401-015-1481-5. PMID: 26423537Free PMC Article

Diagnosis

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
Huo L, Wu Q, Yang F, Liu X, Yang Z, Wang H
Int J Dev Neurosci 2023 Jun;83(4):357-367. Epub 2023 May 18 doi: 10.1002/jdn.10263. PMID: 37203270
Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free 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
O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP; participating investigators
Lancet Neurol 2017 Jan;16(1):33-42. Epub 2016 Nov 10 doi: 10.1016/S1474-4422(16)30294-0. PMID: 27838190

Therapy

Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free PMC Article
Frampton JE
Drugs 2023 Jul;83(10):923-934. Epub 2023 Jun 15 doi: 10.1007/s40265-023-01881-w. PMID: 37316680Free PMC Article
Nam JY, Teng LY, Cho K, Kang HC, Lee JS, Kim HD, Kim SH
Epilepsy Res 2022 Oct;186:106993. Epub 2022 Aug 1 doi: 10.1016/j.eplepsyres.2022.106993. PMID: 35998430
He H, Guzman RE, Cao D, Sierra-Marquez J, Yin F, Fahlke C, Peng J, Stauber T
Epilepsia 2021 Jun;62(6):1401-1415. Epub 2021 May 5 doi: 10.1111/epi.16906. PMID: 33951195
O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP; participating investigators
Lancet Neurol 2017 Jan;16(1):33-42. Epub 2016 Nov 10 doi: 10.1016/S1474-4422(16)30294-0. PMID: 27838190

Prognosis

Jiang L, Bi S, Lin L, He F, Deng F
Mol Genet Genomic Med 2023 Dec;11(12):e2269. Epub 2023 Aug 18 doi: 10.1002/mgg3.2269. PMID: 37593999Free PMC Article
Liu Q, Ma J, Yu G, Zhang Q, Zhu Y, Wang R, Yu H, Liu C, Sun Y, Wang W, Wang S, Ji T, Li M, Liu X, Jiang Y, Cai L, Wu Y
Seizure 2021 Nov;92:29-35. Epub 2021 Aug 14 doi: 10.1016/j.seizure.2021.08.006. PMID: 34416421
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
Nappi P, Miceli F, Soldovieri MV, Ambrosino P, Barrese V, Taglialatela M
Pflugers Arch 2020 Jul;472(7):881-898. Epub 2020 Jun 6 doi: 10.1007/s00424-020-02404-2. PMID: 32506321
O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP; participating investigators
Lancet Neurol 2017 Jan;16(1):33-42. Epub 2016 Nov 10 doi: 10.1016/S1474-4422(16)30294-0. PMID: 27838190

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
Frampton JE
Drugs 2023 Jul;83(10):923-934. Epub 2023 Jun 15 doi: 10.1007/s40265-023-01881-w. PMID: 37316680Free PMC Article
Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE
Neurology 2023 Apr 18;100(16):e1712-e1722. Epub 2023 Feb 7 doi: 10.1212/WNL.0000000000207080. PMID: 36750385Free PMC Article
Liu Q, Ma J, Yu G, Zhang Q, Zhu Y, Wang R, Yu H, Liu C, Sun Y, Wang W, Wang S, Ji T, Li M, Liu X, Jiang Y, Cai L, Wu Y
Seizure 2021 Nov;92:29-35. Epub 2021 Aug 14 doi: 10.1016/j.seizure.2021.08.006. PMID: 34416421
Nappi P, Miceli F, Soldovieri MV, Ambrosino P, Barrese V, Taglialatela M
Pflugers Arch 2020 Jul;472(7):881-898. Epub 2020 Jun 6 doi: 10.1007/s00424-020-02404-2. PMID: 32506321

Recent systematic reviews

Lattanzi S, Trinka E, Russo E, Del Giovane C, Matricardi S, Meletti S, Striano P, Damavandi PT, Silvestrini M, Brigo F
Drugs 2023 Oct;83(15):1409-1424. Epub 2023 Sep 11 doi: 10.1007/s40265-023-01936-y. PMID: 37695433Free PMC Article
Rondão MBA, Hsu BRRHS, Centeno RS, de Aguiar PHP
Seizure 2023 Aug;110:58-68. Epub 2023 Jun 3 doi: 10.1016/j.seizure.2023.04.020. PMID: 37327751
Yates CF, Malone S, Riney K, Shah U, Wood MJ
Pediatr Neurosurg 2023;58(1):18-28. Epub 2023 Jan 13 doi: 10.1159/000529098. PMID: 36693334Free PMC Article
Bailey K, McAdam-Wong D, Im-Bolter N
Brain Lang 2021 Jun;217:104940. Epub 2021 Apr 2 doi: 10.1016/j.bandl.2021.104940. PMID: 33819772
Nevalainen O, Ansakorpi H, Simola M, Raitanen J, Isojärvi J, Artama M, Auvinen A
Neurology 2014 Nov 18;83(21):1968-77. Epub 2014 Oct 22 doi: 10.1212/WNL.0000000000001005. PMID: 25339211

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