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Developmental and epileptic encephalopathy, 28(DEE28)

MedGen UID:
863956
Concept ID:
C4015519
Disease or Syndrome
Synonyms: DEE28; Epileptic encephalopathy, early infantile, 28
 
Gene (location): WWOX (16q23.1-23.2)
 
Monarch Initiative: MONDO:0014533
OMIM®: 616211

Definition

Developmental and epileptic encephalopathy-28 (DEE28) is an autosomal recessive severe neurologic disorder characterized by the onset of refractory seizures in the first months of life. Affected individuals have severe axial hypotonia and profoundly impaired psychomotor development. More severely affected patients have acquired microcephaly, poor or absent visual contact, and retinal degeneration; early death may occur (summary by Mignot et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
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 characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
Abnormal electroretinogram
MedGen UID:
96908
Concept ID:
C0476397
Finding
Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.

Professional guidelines

PubMed

Specchio N, Pietrafusa N, Perucca E, Cross JH
Epilepsy Behav 2022 Jun;131(Pt B):107961. Epub 2021 Apr 16 doi: 10.1016/j.yebeh.2021.107961. PMID: 33867301
Srivastava R, Kirton A
Neoreviews 2021 Mar;22(3):e163-e176. doi: 10.1542/neo.22-3-e163. PMID: 33649089
Nickels K, Kossoff EH, Eschbach K, Joshi C
Epilepsia 2021 Jan;62(1):120-127. Epub 2020 Nov 14 doi: 10.1111/epi.16752. PMID: 33190223

Recent clinical studies

Etiology

Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ
Epilepsia 2021 Mar;62(3):698-708. doi: 10.1111/epi.16821. PMID: 33666943Free 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
Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group
N Engl J Med 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631. PMID: 29768152
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group
Lancet 2018 Mar 17;391(10125):1085-1096. Epub 2018 Jan 26 doi: 10.1016/S0140-6736(18)30136-3. PMID: 29395273
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

Diagnosis

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
Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Srivastava R, Kirton A
Neoreviews 2021 Mar;22(3):e163-e176. doi: 10.1542/neo.22-3-e163. PMID: 33649089
Rochtus A, Olson HE, Smith L, Keith LG, El Achkar C, Taylor A, Mahida S, Park M, Kelly M, Shain C, Rockowitz S, Rosen Sheidley B, Poduri A
Epilepsia 2020 Feb;61(2):249-258. Epub 2020 Jan 19 doi: 10.1111/epi.16427. PMID: 31957018Free PMC Article
D'Antonio F, Pagani G, Familiari A, Khalil A, Sagies TL, Malinger G, Leibovitz Z, Garel C, Moutard ML, Pilu G, Bhide A, Acharya G, Leombroni M, Manzoli L, Papageorghiou A, Prefumo F
Pediatrics 2016 Sep;138(3) doi: 10.1542/peds.2016-0445. PMID: 27581855

Therapy

Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ
Epilepsia 2021 Mar;62(3):698-708. doi: 10.1111/epi.16821. PMID: 33666943Free PMC Article
Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, Nai MH, D'Agostino GA, Tran HD, Itahana Y, Wang D, Lokman H, Itahana K, Lim SWL, Tang J, Chang YY, Zhang M, Cook SA, Rackham OJL, Lim CT, Tan EK, Ng HH, Lim KL, Jiang YH, Je HS
Science 2019 Dec 20;366(6472):1486-1492. doi: 10.1126/science.aav5386. PMID: 31857479Free PMC Article
Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group
N Engl J Med 2018 May 17;378(20):1888-1897. doi: 10.1056/NEJMoa1714631. PMID: 29768152
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, Lyons PD, Taylor A, Roberts C, Sommerville K; GWPCARE4 Study Group
Lancet 2018 Mar 17;391(10125):1085-1096. Epub 2018 Jan 26 doi: 10.1016/S0140-6736(18)30136-3. PMID: 29395273
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

Myers KA
Continuum (Minneap Minn) 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962
Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ
Epilepsia 2021 Mar;62(3):698-708. doi: 10.1111/epi.16821. PMID: 33666943Free PMC Article
Srivastava R, Kirton A
Neoreviews 2021 Mar;22(3):e163-e176. doi: 10.1542/neo.22-3-e163. PMID: 33649089
Nickels K, Kossoff EH, Eschbach K, Joshi C
Epilepsia 2021 Jan;62(1):120-127. Epub 2020 Nov 14 doi: 10.1111/epi.16752. PMID: 33190223
Pisani F, Spagnoli C
Handb Clin Neurol 2019;162:401-414. doi: 10.1016/B978-0-444-64029-1.00019-9. PMID: 31324322

Clinical prediction guides

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
Knupp KG, Scheffer IE, Ceulemans B, Sullivan J, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Agarwal A, Lock M, Dai D, Farfel GM, Galer BS, Gammaitoni AR, Polega S, Davis R, Gil-Nagel A
Epilepsia 2023 Jan;64(1):139-151. Epub 2022 Nov 9 doi: 10.1111/epi.17431. PMID: 36196777Free PMC Article
Vazquez B, Tomson T, Dobrinsky C, Schuck E, O'Brien TJ
Epilepsia 2021 Mar;62(3):698-708. doi: 10.1111/epi.16821. PMID: 33666943Free PMC Article
Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, Devinsky O, Cross JH, Guerrini R, Talwar D, Miller I, Farfel G, Galer BS, Gammaitoni A, Mistry A, Morrison G, Lock M, Agarwal A, Lai WW, Ceulemans B; FAiRE DS Study Group
Lancet 2019 Dec 21;394(10216):2243-2254. Epub 2019 Dec 17 doi: 10.1016/S0140-6736(19)32500-0. PMID: 31862249
D'Antonio F, Pagani G, Familiari A, Khalil A, Sagies TL, Malinger G, Leibovitz Z, Garel C, Moutard ML, Pilu G, Bhide A, Acharya G, Leombroni M, Manzoli L, Papageorghiou A, Prefumo F
Pediatrics 2016 Sep;138(3) doi: 10.1542/peds.2016-0445. PMID: 27581855

Recent systematic reviews

Strzelczyk A, Zuberi SM, Striano P, Rosenow F, Schubert-Bast S
Orphanet J Rare Dis 2023 Mar 1;18(1):42. doi: 10.1186/s13023-023-02626-4. PMID: 36859290Free PMC Article
Spagnoli C, Fusco C, Percesepe A, Leuzzi V, Pisani F
Int J Mol Sci 2021 Apr 18;22(8) doi: 10.3390/ijms22084202. PMID: 33919646Free PMC Article
Pindrik J, Hoang N, Smith L, Halverson M, Wojnaroski M, McNally K, Gedela S, Ostendorf AP
Neurosurg Focus 2018 Sep;45(3):E3. doi: 10.3171/2018.7.FOCUS18220. PMID: 30173613
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
Griessenauer CJ, Salam S, Hendrix P, Patel DM, Tubbs RS, Blount JP, Winkler PA
J Neurosurg Pediatr 2015 Jan;15(1):34-44. doi: 10.3171/2014.10.PEDS14155. PMID: 25380174

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