Comparison of Core Features in Four Developmental Encephalopathies in the Rett Natural History Study.
Adolescent
Brain Diseases
/ diagnosis
Child
Child, Preschool
Epileptic Syndromes
/ diagnosis
Female
Forkhead Transcription Factors
/ genetics
Humans
Male
Mental Retardation, X-Linked
/ diagnosis
Nerve Tissue Proteins
/ genetics
Neurodevelopmental Disorders
/ diagnosis
Rett Syndrome
/ diagnosis
Spasms, Infantile
/ diagnosis
Young Adult
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
13
03
2019
revised:
20
05
2020
accepted:
21
05
2020
pubmed:
31
5
2020
medline:
15
12
2020
entrez:
31
5
2020
Statut:
ppublish
Résumé
Rett syndrome, CDKL5-deficiency disorder, FOXG1 disorder, and MECP2 duplication disorder are developmental encephalopathies with shared and distinct features. Although they are historically linked, no direct comparison has been performed. The first head-to-head comparison of clinical features in these conditions is presented. Comprehensive clinical information was collected from 793 individuals enrolled in the Rett and Rett-Related Disorders Natural History Study. Clinical features including clinical severity, regression, and seizures were cross-sectionally compared between diagnoses to test the hypothesis that these are 4 distinct disorders. Distinct patterns of clinical severity, seizure onset age, and regression were present. Individuals with CDKL5-deficency disorder were the most severely affected and had the youngest age at seizure onset (2 months), whereas children with MECP2 duplication syndrome had the oldest median age at seizure onset (64 months) and lowest severity scores. Rett syndrome and FOGX1 were intermediate in both features. Smaller head circumference correlates with increased severity in all disorders and earlier age at seizure onset in MECP2 duplication syndrome. Developmental regression occurred in all Rett syndrome participants (median = 18 months) but only 23 to 34% of the other disorders. Seizure incidence prior to the baseline visit was highest for CDKL5 deficiency disorder (96.2%) and lowest for Rett syndrome (47.5%). Other clinical features including seizure types and frequency differed among groups. Although these developmental encephalopathies share many clinical features, clear differences in severity, regression, and seizures warrant considering them as unique disorders. These results will aid in the development of disease-specific severity scales, precise therapeutics, and future clinical trials. ANN NEUROL 2020;88:396-406.
Identifiants
pubmed: 32472944
doi: 10.1002/ana.25797
pmc: PMC8882337
mid: NIHMS1775196
doi:
Substances chimiques
FOXG1 protein, human
0
Forkhead Transcription Factors
0
Nerve Tissue Proteins
0
Types de publication
Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
396-406Subventions
Organisme : NICHD NIH HHS
ID : U54 HD083211
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD061222
Pays : United States
Organisme : Vanderbilt Intellectual and Developmental Disabilities Research Center
ID : U54HD083211
Pays : International
Organisme : NIH National Institutes of Child Health and Disease
ID : 3 U54-HD061222-14S1
Pays : International
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Informations de copyright
© 2020 American Neurological Association.
Références
Am J Med Genet A. 2004 Apr 15;126A(2):129-40
pubmed: 15057977
Pediatr Neurol. 2019 Aug;97:18-25
pubmed: 30928302
Clin Genet. 2017 Apr;91(4):557-563
pubmed: 27247049
Pediatr Neurol. 2013 May;48(5):367-77
pubmed: 23583054
Am J Med Genet A. 2010 May;152A(5):1079-88
pubmed: 20425814
Epilepsy Res. 2018 Sep;145:134-139
pubmed: 29966812
Epilepsia. 2012 Dec;53(12):2067-78
pubmed: 22998673
Epilepsia. 2015 Apr;56(4):569-76
pubmed: 25789914
J Pediatr. 2010 Jun;156(6):907-913.e2
pubmed: 20304425
Stat Med. 1998 Feb 28;17(4):407-29
pubmed: 9496720
Pediatr Neurol. 2019 Aug;97:38-42
pubmed: 31147226
Pediatr Neurol. 2017 Nov;76:37-46
pubmed: 28964591
Genet Med. 2018 Jan;20(1):98-108
pubmed: 28661489
Neurology. 2008 Mar 11;70(11):868-75
pubmed: 18332345
J Child Neurol. 2015 Nov;30(13):1743-8
pubmed: 25895911
Neurology. 2010 Mar 16;74(11):909-12
pubmed: 20231667
Epilepsia. 2010 Jul;51(7):1252-8
pubmed: 20491871
J Med Genet. 2018 Jun;55(6):359-371
pubmed: 29618507
Brain. 2008 Oct;131(Pt 10):2647-61
pubmed: 18790821
Ann Neurol. 2010 Dec;68(6):944-50
pubmed: 21154482
Neurol Genet. 2018 Nov 07;4(6):e281
pubmed: 30533527
J Med Genet. 2014 Mar;51(3):152-8
pubmed: 24399845
J Med Genet. 2006 Sep;43(9):729-34
pubmed: 16611748
Neurology. 2008 Apr 15;70(16):1313-21
pubmed: 18337588
Eur J Paediatr Neurol. 2007 Sep;11(5):310-7
pubmed: 17433737
Brain. 2017 Feb;140(2):306-318
pubmed: 28007990
Clin Genet. 2009 Oct;76(4):357-71
pubmed: 19793311
J Med Genet. 2005 Feb;42(2):103-7
pubmed: 15689447
Epilepsia. 2019 Aug;60(8):1733-1742
pubmed: 31313283
Brain Res. 2017 Nov 15;1675:71-77
pubmed: 28870827
Eur J Paediatr Neurol. 2014 Jul;18(4):475-81
pubmed: 24703762
Epilepsy Behav. 2010 Nov;19(3):296-300
pubmed: 20728410
Neurology. 2019 Apr 16;92(16):e1912-e1925
pubmed: 30918097
J Med Genet. 2011 Jun;48(6):396-406
pubmed: 21441262
Orphanet J Rare Dis. 2016 Apr 14;11:39
pubmed: 27080038
J Pediatr. 2006 Mar;148(3):347-52
pubmed: 16615965
Epilepsia. 2008 Jun;49(6):1027-37
pubmed: 18266744
Clin Genet. 2019 May;95(5):575-581
pubmed: 30788845
Eur J Hum Genet. 2013 Mar;21(3):266-73
pubmed: 22872100