Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.
Pediatrics
; 126(2): e391-400, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20643727
ABSTRACT
OBJECTIVES:
We describe the first cohort-based analysis of the impact of genetic disorders in craniosynostosis. We aimed to refine the understanding of prognoses and pathogenesis and to provide rational criteria for clinical genetic testing.METHODS:
We undertook targeted molecular genetic and cytogenetic testing for 326 children who required surgery because of craniosynostosis, were born in 1993-2002, presented to a single craniofacial unit, and were monitored until the end of 2007.RESULTS:
Eighty-four children (and 64 relatives) had pathologic genetic alterations (86% single-gene mutations and 14% chromosomal abnormalities). The FGFR3 P250R mutation was the single largest contributor (24%) to the genetic group. Genetic diagnoses accounted for 21% of all craniosynostosis cases and were associated with increased rates of many complications. Children with an initial clinical diagnosis of nonsyndromic craniosynostosis were more likely to have a causative mutation if the synostoses were unicoronal or bicoronal (10 of 48 cases) than if they were sagittal or metopic (0 of 55 cases; P = .0003). Repeat craniofacial surgery was required for 58% of children with single-gene mutations but only 17% of those with chromosomal abnormalities (P = .01).CONCLUSIONS:
Clinical genetic assessment is critical for the treatment of children with craniosynostosis. Genetic testing of nonsyndromic cases (at least for FGFR3 P250R and FGFR2 exons IIIa/c) should be targeted to patients with coronal or multisuture synostoses. Single-gene disorders that disrupt physiologic signaling in the cranial sutures often require reoperation, whereas chromosomal abnormalities follow a more-indolent course, which suggests a different, secondary origin of the associated craniosynostosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação Puntual
/
Craniossinostoses
/
Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
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Doenças Genéticas Inatas
Tipo de estudo:
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Infant
/
Newborn
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article