80
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Craniosynostosis genetics: The mystery unfolds

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Craniosynsostosis syndromes exhibit considerable phenotypic and genetic heterogeneity. Sagittal synostosis is common form of isolated craniosynostosis. The sutures involved, the shape of the skull and associated malformations give a clue to the specific diagnosis. Crouzon syndrome is one of the most common of the craniosynostosis syndromes. Apert syndrome accounts for 4.5% of all craniosynostoses and is one of the most serious of these syndromes. Most syndromic craniosynostosis require multidisciplinary management. The following review provides a brief appraisal of the various genes involved in craniosynostosis syndromes, and an approach to diagnosis and genetic counseling.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: not found
          • Article: not found

          Online Mendelian Inheritance in Man.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Neurodevelopment of children with single suture craniosynostosis: a review.

            Rates of neurocognitive risk range from 35-50% of school-aged children with isolated single suture craniosynostosis (SSC). It has been hypothesized that early surgical intervention to release suture fusion reduces risk for increased intracranial pressure (ICP) and the corresponding risk to neurodevelopment. However, studies assessing children with SSC have been inconsistent in finding an association between neurocognitive development, age of surgery, and ICP. SSC produces notable distortion of the cranial vault and underlying brain mass. Although a linear relationship between skull distortion, ICP, and neurocognitive deficits has generally been assumed, recent studies have postulated an interactive process between the skull and developing brain that results in neuroanatomical changes that are not limited to areas directly beneath the fused suture. The specific neuropsychological deficits identified in children with SSC including problems with attention and planning, processing speed, visual spatial skills, language, reading, and spelling may be related to the anatomic differences that persist after correction of suture fusion. Available literature on neurocognitive development of children with SSC is suggestive of mild but persistent neuropsychological deficits, which become more significant as cognitive demands increase at school age. Anatomical studies of children without SSC are beginning to identify particular groups of brain structures that if disrupted or malformed, may be associated with specific cognitive deficits. Controlled research investigating the relationship between persistent anatomical changes and neurocognitive functioning of school-aged children with SSC is needed.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The molecular basis of Boston-type craniosynostosis: the Pro148-->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences.

              Craniosynostosis, Boston type is an autosomal dominant disorder that results in the premature fusion of calvarial bones and ensuing abnormalities in skull shape. We showed previously that this disorder is tightly linked to the Msx2 homeobox gene on the long arm of chromosome 5, and that affected individuals bear a mutated copy of Msx2. In addition, transgenic mice in which either mutant or wild-type mouse Msx2 is overexpressed in the developing skull also exhibit craniosynostosis. That both mutant and wild-type Msx2 elicit craniosynostosis in transgenic mice and that the Boston type mutation is dominant led us to hypothesize that the mutation might enhance the normal function of Msx2. The mutation is located in position 7 of the N-terminal arm of the homeodomain, a region implicated in both target sequence recognition and protein-protein interactions. Here we test the hypothesis that the Pro148-->His mutation alters the DNA binding properties of Msx2. Using gel shift and binding site selection analyses, we show that the mutation enhances the affinity of Msx2 for a set of known Msx2 target sequences but has little or no effect on the site specificity of Msx2 binding. The enhancement of Msx2 binding is due largely if not entirely to an increased stability of the mutant Msx2-DNA complex. These data provide a molecular-level explanation of how the Pro148-->His mutation enhances Msx2 function and thus leads to the dominant craniosynostosis phenotype.
                Bookmark

                Author and article information

                Journal
                Indian J Hum Genet
                IJHG
                Indian Journal of Human Genetics
                Medknow Publications (India )
                0971-6866
                1998-362X
                May-Aug 2011
                : 17
                : 2
                : 48-53
                Affiliations
                [1]Department of Pediatrics, Genetic and Metabolic Unit, Advanced Pediatric Center, PGIMER, Chandigarh, India
                Author notes
                Address for correspondence: Dr. Inusha Panigrahi, Genetic and Metabolic Unit, Advanced Pediatric Center, PGIMER, Sec-12, Chandigarh, India. E-mail: inupan@ 123456yahoo.com
                Article
                IJHG-17-48
                10.4103/0971-6866.86171
                3214317
                22090712
                64447e57-ccab-4757-9c97-ae305dbac183
                Copyright: © Indian Journal of Human Genetics

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Review Article

                Genetics
                syndromes,hydrocephalus,sutural synostosis,plagiocephaly,fgfr2 mutations,apert syndrome
                Genetics
                syndromes, hydrocephalus, sutural synostosis, plagiocephaly, fgfr2 mutations, apert syndrome

                Comments

                Comment on this article