A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity.
Mol Psychiatry
; 24(2): 241-251, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-29892053
ABSTRACT
Epilepsy and Mental Retardation Limited to Females (EFMR) is an infantile onset disorder characterized by clusters of seizures. EFMR is due to mutations in the X-chromosome gene PCDH19, and is underpinned by cellular mosaicism due to X-chromosome inactivation in females or somatic mutation in males. This review characterizes the neuropsychiatric profile of this disorder and examines the association of clinical and molecular factors with neuropsychiatric outcomes. Data were extracted from 38 peer-reviewed original articles including 271 individual cases. We found that seizure onset ≤12 months was significantly associated (p = 4.127 × 10-7) with more severe intellectual disability, compared with onset >12 months. We identified two recurrent variants p.Asn340Ser and p.Tyr366Leufs*10 occurring in 25 (20 unrelated) and 30 (11 unrelated) cases, respectively. PCDH19 mutations were associated with psychiatric comorbidities in approximately 60% of females, 80% of affected mosaic males, and reported in nine hemizygous males. Hyperactive, autistic, and obsessive-compulsive features were most frequently reported. There were no genotype-phenotype associations in the individuals with recurrent variants or the group overall. Age at seizure onset can be used to provide more informative prognostic counseling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espasmos Infantis
/
Caderinas
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Epilepsia
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Mol Psychiatry
Assunto da revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália