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Advances in Experimental Medicine and... 2008In recent years molecular genetics has revolutionized the study of somitogenesis in developmental biology and advances that have taken place in animal models have been... (Review)
Review
In recent years molecular genetics has revolutionized the study of somitogenesis in developmental biology and advances that have taken place in animal models have been applied successfully to human disease. Abnormal segmentation in man is a relatively common birth defect and advances in understanding have come through the study of cases clustered in families using DNA linkage analysis and candidate gene approaches, the latter stemming directly from knowledge gained through the study of animal models. Only a minority of abnormal segmentation phenotypes appear to follow Mendelian inheritance but three genes--DLL3, MESP2 and LNFG--have now been identified for spondylocostal dysostosis (SCD), a spinal malformation characterized by extensive hemivertebrae, trunkal shortening and abnormally aligned ribs with points of fusion. In affected families autosomal recessive inheritance is followed. These genes are all important components of the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. This review deals mainly with SCD, with some consideration of AGS. Significant future challenges lie in identifying causes of the many abnormal segmentation phenotypes in man but it is hoped that combined approaches in collaboration with developmental biologists will reap rewards.
Topics: Alagille Syndrome; Basic Helix-Loop-Helix Transcription Factors; Body Patterning; Bone Diseases, Developmental; Calcium-Binding Proteins; Dysostoses; Glycosyltransferases; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mutation; Phenotype; Receptors, Notch; Serrate-Jagged Proteins; Signal Transduction; Somites; Spine
PubMed: 21038776
DOI: 10.1007/978-0-387-09606-3_9 -
Developmental Dynamics : An Official... Jun 2007Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal... (Review)
Review
Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.
Topics: Animals; Disease Susceptibility; Dysostoses; Humans; Phenotype; Receptors, Notch; Signal Transduction; Spine
PubMed: 17497699
DOI: 10.1002/dvdy.21182 -
American Journal of Medical Genetics Apr 1992
Topics: Abnormalities, Multiple; Dysostoses; Humans; Infant, Newborn; Syndrome
PubMed: 1637382
DOI: 10.1002/ajmg.1320420621 -
Plastic and Reconstructive Surgery Sep 1974
Topics: Adolescent; Cephalometry; Child; Craniofacial Dysostosis; Diagnosis, Differential; Exophthalmos; Female; Humans; Male; Malocclusion; Methods; Osteotomy
PubMed: 4850935
DOI: 10.1097/00006534-197409000-00007 -
Current Topics in Developmental Biology 2014Hes genes, encoding basic helix-loop-helix (HLH) transcriptional repressors, are mammalian homologues of Drosophila hairy and Enhancer of split genes, both of which are... (Review)
Review
Hes genes, encoding basic helix-loop-helix (HLH) transcriptional repressors, are mammalian homologues of Drosophila hairy and Enhancer of split genes, both of which are required for normal neurogenesis in Drosophila. There are seven members in the human Hes family, Hes1-7, which are expressed in many tissues and play various roles mainly in development. All Hes proteins have three conserved domains: basic HLH (bHLH), Orange, and WRPW domains. The basic region binds to target DNA sequences, while the HLH region forms homo- and heterodimers with other bHLH proteins, the Orange domain is responsible for the selection of partners during heterodimer formation, and the WRPW domain recruits corepressors. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction. Hes factors regulate many events in development by repressing the expression of target genes, many of which encode transcriptional activators that promote cell differentiation. For example, Hes1, Hes3, and Hes5 are highly expressed by neural stem cells, and inactivation of these genes results in insufficient maintenance of stem cell proliferation and prematurely promotes neuronal differentiation. Recently, it was shown that the expression dynamics of Hes1 plays crucial roles in proper developmental timings and fate-determination steps of embryonic stem cells and neural progenitor cells. Here, we discuss some key features of Hes factors in development and diseases.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Brain; Cell Differentiation; Cell Proliferation; Cells, Cultured; Central Nervous System; DNA-Binding Proteins; Dysostoses; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Mice; Multigene Family; Ribs; Scoliosis; Spine; Transcription Factor HES-1; Transcription Factors
PubMed: 25248479
DOI: 10.1016/B978-0-12-405943-6.00007-5 -
Current Opinion in Otolaryngology &... Aug 2012Syndromic craniofacial dysostosis remains one of the most challenging diagnoses in congenital craniomaxillofacial surgery. Distraction osteogenesis has held the promise... (Review)
Review
PURPOSE OF REVIEW
Syndromic craniofacial dysostosis remains one of the most challenging diagnoses in congenital craniomaxillofacial surgery. Distraction osteogenesis has held the promise of greater facial movements with improved stability, less morbidity and more favorable functional and esthetic outcomes. Current literature is starting to determine whether this promise is being fulfilled.
RECENT FINDINGS
The current trend in the literature is increasing indications for distraction in treating syndromic synostosis. Posterior vault, anterior vault, early monobloc and segmental Lefort distraction techniques are being advocated as alternatives to traditional surgeries. Outcome analysis of distraction techniques is becoming more common, especially in the assessment of obstructive sleep apnea and advancement stability.
SUMMARY
Distraction osteogenesis has challenged, and in many centers modified, the treatment algorithms for craniofacial dysostoses that had been based on traditional osteotomy techniques. In some cases, distraction osteogenesis has encouraged earlier, more aggressive surgeries; in others, it has served as a temporizing measure to allow subsequent traditional surgeries to be performed at a more favorable age. As craniofacial distraction osteogenesis evolves and we become more critical in our outcome analysis, we may find more favorable long-term results compared with traditional techniques in aspects such as premature aging, bone healing and degree of advancement.
Topics: Algorithms; Arnold-Chiari Malformation; Child; Child, Preschool; Craniofacial Dysostosis; Craniosynostoses; Facial Bones; Follow-Up Studies; Humans; Infant; Orbit; Osteogenesis, Distraction; Osteotomy; Osteotomy, Le Fort; Postoperative Complications; Reoperation; Secondary Prevention; Skull; Skull Base
PubMed: 22894998
DOI: 10.1097/MOO.0b013e3283543a43 -
Pediatric Radiology Mar 2003Although many constitutional disorders of bone are individually rare, collectively they make up a large group of disorders. They are broadly classified into... (Review)
Review
Although many constitutional disorders of bone are individually rare, collectively they make up a large group of disorders. They are broadly classified into osteochondrodysplasias and dysostoses. Because of the rarity of some of these conditions, they can be difficult to diagnose. Members of the International Dysplasia Group meet regularly to update and clarify the nomenclature. The last meeting was in Oxford in 2001. This article attempts to highlight the differences between the osteochondrodysplasias and the dysostoses, and provides a systematic approach to their radiological diagnosis.
Topics: Bone Diseases, Developmental; Bone and Bones; Child, Preschool; Dysostoses; Female; Humans; Infant; Male; Osteochondrodysplasias; Radiography; Sensitivity and Specificity; Societies, Medical; Terminology as Topic
PubMed: 12612812
DOI: 10.1007/s00247-002-0855-8 -
Clinical Genetics Apr 1991Jarcho-Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory...
Jarcho-Levin syndrome is a variety of autosomal recessive spondylocostal dysostosis characterized by severe deformity of the thoracic cage, leading to respiratory failure and early death. There are often associated dysmorphic features. The disease is more frequent in Puerto Ricans and rare in Europe. A Sicilian family with four affected individuals in two interrelated sibships is reported.
Topics: Abnormalities, Multiple; Cervical Vertebrae; Chromosome Aberrations; Chromosome Disorders; Dysostoses; Female; Genes, Recessive; Humans; Infant, Newborn; Kyphosis; Pedigree; Ribs; Spinal Osteophytosis; Syndrome; Thoracic Vertebrae
PubMed: 2070546
DOI: 10.1111/j.1399-0004.1991.tb03023.x -
Revue Medicale de Liege Sep 2004Spondylocostal dysostoses represent a group of very rare genetic disorders, characterised by vertebral and costal segmentation defects, sometimes accompanied by visceral... (Review)
Review
Spondylocostal dysostoses represent a group of very rare genetic disorders, characterised by vertebral and costal segmentation defects, sometimes accompanied by visceral malformations. The major gene involved is DLL3, on chromosome 19. A mutation may lead to a somitogenesis defect, with segmentation defect of axial skeleton and deformations. Depending on the nature of the mutation of DLL3, spondylocostal dysostosis is transmitted as an autosomal dominant (less severe) or autosomal recessive trait (often more severe, but non lethal). Spondylocostal dysostoses must not to be confused with the Jarcho-Levin spondylothoracic dysostosis, a severe, autosomal recessive syndrome. Its most typical aspect is the crab-like appearance of the rib cage leading to major respiratory disorders. Death, due to respiratory insufficiency, usually occurs before the age of two, most often during the first few months. At this time, guidelines for treatment do not exist. We report a case of spondylocostal dysosotosis in a patient born to consanguineous turkish parents, and review the clinical and genetic data on that group of skeletal disorders.
Topics: Abnormalities, Multiple; Dysostoses; Humans; Infant, Newborn; Male; Ribs; Spinal Diseases
PubMed: 15562550
DOI: No ID Found -
American Journal of Medical Genetics Jun 1986We describe a Bayesian method of estimating penetrance from genealogical data. It consists of calculating the likelihood of the data alone to make inferences about...
We describe a Bayesian method of estimating penetrance from genealogical data. It consists of calculating the likelihood of the data alone to make inferences about penetrance without sample space considerations. The method is applied to mandibulofacial dysostosis giving a penetrance of 0.908 with 0.95 credible interval of [0.809; 0.972] and to frontonasal dysostosis giving a penetrance of 0.670 with 0.95 credible interval of [0.457; 0.851].
Topics: Craniofacial Dysostosis; Gene Expression Regulation; Genetics, Medical; Genotype; Humans; Mandibulofacial Dysostosis; Pedigree; Phenotype; Probability; Statistics as Topic
PubMed: 3717208
DOI: 10.1002/ajmg.1320240204