RESUMEN
Apert syndrome is an autosomal dominant condition characterized by craniosynostosis and severe syndactyly, caused by two recurrent mutations in the fibroblast growth factor receptor 2 gene (FGFR2). The genotype-phenotype correlations of 21 patients with Apert syndrome were analysed as to the craniofacial appearance following surgery and the degree of syndactlyly. The craniofacial appearance following craniofacial surgery was better in patients with the P253R mutation, whereas these patients showed a more pronounced severity of the syndactyly.
Asunto(s)
Acrocefalosindactilia/genética , Mutación , Sindactilia/genética , Acrocefalosindactilia/cirugía , Craneotomía , Facies , Femenino , Genotipo , Humanos , Lactante , Masculino , Fenotipo , Proteínas Tirosina Quinasas Receptoras/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/genética , Resultado del TratamientoRESUMEN
The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal dominant disorders with significant clinical overlap. Recently, we described a large family with autosomal dominant craniosynostosis suggestive of Saethre-Chotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had been excluded. We now report the presence of a mutation in the fibroblast growth factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been previously reported in 10 patients with non-syndromic craniosynostosis. Variable expression of this mutation is evident especially in two additional members of this family, one of whom is severely affected with pancraniosynostosis. The family provides a further example of genetic heterogeneity and variable expression of the craniosynostosis syndromes and broadens the phenotypic spectrum associated with the FGFR3 mutation P250R. In addition, we found a polymorphism (F384L) in the transmembrane domain of FGFR3 which occurs with a frequency of 3% in the Turkish population but is uncommon among Germans.
Asunto(s)
Craneosinostosis/genética , Proteínas Tirosina Quinasas , Receptores de Factores de Crecimiento de Fibroblastos/genética , Femenino , Ligamiento Genético , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Linaje , Fenotipo , Receptor Tipo 3 de Factor de Crecimiento de FibroblastosRESUMEN
We describe the clinical manifestations of an autosomal dominant form of craniosynostosis in a large family with eight affected relatives. Unilateral or bilateral coronal synostosis, low frontal hair line, strabismus, ptosis, and partial cutaneous syndactyly of fingers and toes are findings suggestive of the diagnosis of Saethre-Chotzen syndrome. The disease locus was excluded from the two adjacent Saethre-Chotzen candidate regions on 7p by linkage analysis with markers D7S664 and D7S507. This indicates heterogeneity of Saethre-Chotzen syndrome with a locus outside the candidate regions on 7p.