Tuberous Sclerosis Complex Genotypes and Developmental Phenotype.
Cognition
Developmental delay
Genotype
Genotype-phenotype correlation
Mullen scales of early learning (MSEL)
Phenotype
Tuberous sclerosis complex (TSC)
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
29
11
2018
revised:
25
02
2019
accepted:
06
03
2019
pubmed:
22
4
2019
medline:
2
5
2020
entrez:
22
4
2019
Statut:
ppublish
Résumé
Children with tuberous sclerosis complex (TSC), caused by pathogenic variants in TSC1/TSC2, are at risk for intellectual disability. TSC2 pathogenic variants appear to increase the risk, compared with TSC1. However, the effect of TSC2 pathogenic variants on early and specific domains of development hasn't been studied. Using an extensively phenotyped group, we aimed to characterize differences in early intellectual development between genotypes. The study group (n = 92) included participants with TSC enrolled in a multicenter study involving genetic testing and detailed prospective phenotyping including the Mullen Scales of Early Learning, a validated measure of cognition, language, and motor development in babies and preschool children. Mean T-scores at 24 months for each Mullen Scales of Early Learning domain were calculated for children with, versus without, a TSC2 pathogenic variant. Multivariable linear regression models were used to compare the groups, adjusting for seizures. T-scores on every Mullen Scales of Early Learning domain were significantly worse in the TSC2 group. Below average composite scores were present in three-fourths of the TSC2 group, compared with one-fourth of those without TSC2. Having a TSC2 pathogenic variant was associated with lower composite Mullen Scales of Early Learning scores, even when corrected for seizures. In a well-characterized patient population with standardized assessment of multiple aspects of development, we found that having a TSC2 pathogenic variant was associated with significantly lower Mullen Scales of Early Learning scores at age 24 months, independent of seizures. These data suggest that a baby with a TSC2 pathogenic variant is at high risk for significant developmental delays by 24 months.
Sections du résumé
BACKGROUND
Children with tuberous sclerosis complex (TSC), caused by pathogenic variants in TSC1/TSC2, are at risk for intellectual disability. TSC2 pathogenic variants appear to increase the risk, compared with TSC1. However, the effect of TSC2 pathogenic variants on early and specific domains of development hasn't been studied. Using an extensively phenotyped group, we aimed to characterize differences in early intellectual development between genotypes.
METHODS
The study group (n = 92) included participants with TSC enrolled in a multicenter study involving genetic testing and detailed prospective phenotyping including the Mullen Scales of Early Learning, a validated measure of cognition, language, and motor development in babies and preschool children. Mean T-scores at 24 months for each Mullen Scales of Early Learning domain were calculated for children with, versus without, a TSC2 pathogenic variant. Multivariable linear regression models were used to compare the groups, adjusting for seizures.
RESULTS
T-scores on every Mullen Scales of Early Learning domain were significantly worse in the TSC2 group. Below average composite scores were present in three-fourths of the TSC2 group, compared with one-fourth of those without TSC2. Having a TSC2 pathogenic variant was associated with lower composite Mullen Scales of Early Learning scores, even when corrected for seizures.
CONCLUSIONS
In a well-characterized patient population with standardized assessment of multiple aspects of development, we found that having a TSC2 pathogenic variant was associated with significantly lower Mullen Scales of Early Learning scores at age 24 months, independent of seizures. These data suggest that a baby with a TSC2 pathogenic variant is at high risk for significant developmental delays by 24 months.
Identifiants
pubmed: 31005478
pii: S0887-8994(18)31292-X
doi: 10.1016/j.pediatrneurol.2019.03.003
pmc: PMC6837240
mid: NIHMS1045432
pii:
doi:
Substances chimiques
TSC1 protein, human
0
TSC2 protein, human
0
Tuberous Sclerosis Complex 1 Protein
0
Tuberous Sclerosis Complex 2 Protein
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
58-63Subventions
Organisme : NINDS NIH HHS
ID : U01 NS082320
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092090
Pays : United States
Investigateurs
M Sahin
(M)
D Krueger
(D)
M Bebin
(M)
J Y Wu
(JY)
H Northrup
(H)
S Warfield
(S)
J Peters
(J)
B Scherrer
(B)
M Goyal
(M)
R Filip-Dhima
(R)
K Dies
(K)
S Bruns
(S)
E Hanson
(E)
N Bing
(N)
B Kent
(B)
S O'Kelley
(S)
M E Williams
(ME)
D Pearson
(D)
G Cutter
(G)
S Roberds
(S)
D S Murray
(DS)
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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