title: Craniosynostosis associated with ocular and distal limb defects is very likely caused by mutations in a gene different from FGFR, TWIST, and MSX2.
abstract: Craniosynostosis caused by genetic factors includes a heterogeneous group of over 100 syndromes, most with autosomal dominant inheritance. Mutations in five genes (FGFR1-, -2, -3, TWIST, and MSX2) causing craniosynostosis as the main clinical feature were described. In most of these conditions, there are also limb malformations. We report a two-generation kindred segregating microcornea, optic nerve alterations and cataract since childhood, craniosynostosis, and distal limb alterations, with a great clinical intrafamilial variability. The ophthalmological problems here described seem to be unique to this genealogy while similar feet alterations were apparently only described in two other affected siblings with acro-cranial-facial dysostosis syndrome (ADS). However, ADS has an autosomal recessive inheritance instead of the dominant pattern of the present genealogy. The candidate exons of the five genes previously mentioned were tested through sequencing analysis presenting normal results in all cases. Therefore, clinical and laboratory analyses in our patients suggest that their phenotype represents a new syndrome very likely caused by mutation in a gene different from those studied.
authors.affiliation: Centro de Estudo do Genoma Humano, Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil. passos@ib.usp.br
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
authors.forename: Lucia Maria
authors.initials: LM
authors.lastname: Armelin
authors.forename: Luís Garcia
authors.initials: LG
authors.lastname: Alonso
authors.forename: Isaac
authors.initials: I
authors.lastname: Neustein
authors.forename: Andréa L
authors.initials: AL
authors.lastname: Sertié
authors.forename: Kikue
authors.initials: K
authors.lastname: Abe
authors.forename: Rita de Cássia
authors.initials: Rde C
authors.lastname: Pavanello
authors.forename: Lívia C
authors.initials: LC
authors.lastname: Elkis
authors.forename: Célia P
authors.initials: CP
authors.lastname: Koiffmann
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics; D005128:Eye Diseases / Q000150:complications*; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D017880:Limb Deformities, Congenital / Q000150:complications*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D009687:Nuclear Proteins; D017468:Receptors, Fibroblast Growth Factor; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D004247:DNA; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3