Methylenetetrahydrofolate reductase C677T variant in Indian children with craniosynostosis: Its role in the pathogenesis, risk of craniosynostosis.

BACKGROUND : 677C to T allele in the 5, 10‑methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the etiology of various syndromes and nonsyndromic diseases but till date no direct studies have been reported with craniosynostosis. OBJECTIVES: The aim was to study the family‑based association of MTHFR polymorphism in different categories of craniosynostosis patients. MATERIALS AND METHODS: This was a cross‑sectional study in which 30 patients classified as Apert syndrome, Pfeiffr syndrome and nonsyndromic craniosynostosis patients with their family were recruited. A sample of 3 ml intravenous blood was taken from patients and from their family members (father and mother) in ethylenediaminetetraacetic acid‑anticoagulated vacutainer for the purpose of the study. Genomic DNA was extracted from peripheral blood lymphocytes by phenol chloroform extraction method. Primers for MTHFR gene were designed. The polymerase chain reaction was carried out. After successful amplification, a small aliquot (5 µl) of the MTHFR reaction mixture was treated with 1 units of Hinf I restriction enzyme (NEB). Results were obtained and compiled. RESULTS: A total of 30 patients/participants with craniosynostosis of Indian descent and their parents formed the study group. The genotyping did not confirm an association between the MTHFR 677C to T polymorphism and between different categories of craniosynostosis. When comparing the offspring of mothers statistically significant differences were found. CONCLUSION: C667T polymorphism of the MTHFR gene is unlikely to play a role in the pathogenesis of craniosynostosis though maternal MTHFR C677T polymorphism may be a genetic risk factor.

Effects of uterine cervix constriction on Wistar rats / Efeitos da constrição do cérvix uterino em ratos Wistar

PURPOSE: To verify if uterine cerclage can induce craniosynostosis or any cranial deformity in new born Wistar rats. METHODS: One pregnant female Wistar rat underwent laparotomy on day 18 of gestation and the uterus cervix was closed with a 3-0 nylon suture to avoid delivery, that occurs normally on the 21 day. The suture was released after 48 hours beyond the normal gestation period. The female rat delivered 11 pups. Six surviving rats from the delivery (group A - constrained group). Two rats were born from another mother and in the same age were used as control group (group B - 2 nonconstrained controls) were allowed to grow. They were sacrificed 1.2 years after their birth all the eight animals. Linear measurement, routine histology and computed tomography of the skull were performed at the time of their death to evaluate the cranial asymmetries by mesurements of the anatomical landmarks of the craniofacial skeleton of the rats on the two groups and compared then. RESULTS: We did not observe statistically significant differences in any of the compared measurements (p>0.05) obtained through the morphologic and radiologic methods. Histologic examinations did not reveal any sign of premature fusion or suture imbrications. Critical decrease in longitudinal body size was noticed as the limbs too in all the animals of group A. CONCLUSION: Constriction of uterine cervix leads to fetus suffering, even death for a few animals, associated to small body size, but not to craniosynostosis.

OBJETIVO: Verificar se a cerclagem intra-uterina pode induzir, ao nascimento de ratos Wistar, craniossinostose ou qualquer outra deformidade craniana. MÉTODOS: Uma rata Wistar prenhe foi submetida à laparotomia no 18º dia de gestação e o cérvix uterino foi suturado com 3-0 nylon, impedindo o parto normal que normalmente ocorre no 21º dia de gestação. A sutura foi liberada 48 horas após o período gestacional normal. A rata gestante deu à luz 11 animais. Seis ratos sobreviveram ao parto (grupo A com restrição). Dois ratos nascidos de outra mãe e com a mesma idade foram utilizados como controle (grupo B sem restrição controle) durante o seu crescimento. Os oito animais foram sacrificados após 1,2 ano. Medidas lineares, histologia e tomografia computadorizada foram utilizadas para a aferição de assimetrias cranianas através da mensuração de pontos anatômicos do esqueleto craniofacial dos ratos dos dois grupos. RESULTADOS: Não foi observada diferença estatisticamente significante entre as medidas obtidas nos ratos dos dois grupos (p>0,05) obtidas através de métodos morfológicos e radiológicos. As análises histológicas não revelaram sinais de fusão prematura da suturas do crânio. Diminuição do segmento corpóreo, bem como do tamanho dos membros foi evidenciado em todos os animais do grupo A. CONCLUSÃO: A restrição do cérvix uterino levou ao sofrimento fetal, morte de alguns animais e diminuição do tamanho do corpo de todos os animais, mas não craniossinostose.

case of fetal valproate syndrome with new features expanding the phenotype

Fetal valproate syndrome [FVS] is a well-recognized constellation of dysmorphic features, and neurodevelopmental retardation that results from prenatal exposure to the anticonvulsant valproic acid. In this report, we describe a case with typical features of FVS. A 23-year-old lady with post-traumatic epilepsy controlled by sodium valproate [Depakene] 500 mg twice daily throughout pregnancy as monotherapy, gave birth to a female baby with facial features characteristic of FVS, and severe radial ray reduction. She also had wide-spaced nipples and short neck, features not described before. Sodium valproate, a widely used anticonvulsant and mood regulator, is a well-recognized teratogen that can result in severe limb deformities, craniosynostosis, neural tube defects and neurodevelopmental retardation. Therefore, we recommend that valproic acid must be avoided during pregnancy, as new generation of anticonvulsant drugs have emerged into the market

Craniossinostoses primárias: ensaio iconográfico / Primary craniosynostosis: iconographic essay

A primeira revisão das ossificações prematuras das suturas da calvária e seus efeitos na forma e aparência do crânio data de 1858, tendo sido publicada por Virchow, que as denominou de craniossinostoses. Quando uma configuração anormal da calvária é detectada, a avaliação radiológica é necessária para caracterizar a deformidade e para guiar o procedimento cirúrgico corretivo. Sabe-se que há uma melhora significativa em crianças afetadas quando o diagnóstico e a intervenção cirúrgica ocorrem o mais cedo possível. A tomografia com reconstrução tridimensional avalia a presença e o grau de envolvimento de cada sutura e permite avaliar anormalidades faciais e intracraniais associadas. Este resumo iconográfico ilustra os achados de imagem, nomenclatura e anormalidades associadas aos vários tipos de craniossinostoses primárias.

Premature ossification of skull's sutures and its effects on the shape and appearance of the head was first reviewed in 1858 by Virchow, who named it craniosynostosis. When there is abnormal configuration of the skull, radiological evaluation must be done in order to characterize the deformity and to guide surgical corrective procedures. It is well known that a significant improvement is seen in children with early diagnosis and surgical intervention. Computed tomography 3-D reconstructions allow the evaluation of the degree of involvement of each suture and associated facial and intracranial anomalies. In this pictorial review we illustrate the image findings and discuss the nomenclature and the anomalies associated with the several types of primary craniosynostosis.

The pathogenesis of craniosynostosis in the fetus

Craniosynostosis occurs in approximately 1:2000 live births. It may affect the coronal, sagittal, metopic and lambdoid sutures in isolation or in combination. Although non-syndromic synostoses are more common, over 150 genetic syndromes have been identified. Recent advances in genetic mapping have linked chromosomal mutations with craniosynostotic syndromes. Despite the identification of these genetic mutations, the fundamental biomolecular mechanisms mediating cranial suture biology remain unknown. Today, many laboratories are investigating murine cranial suture biology as a model for human cranial suture development and fusion. Normal murine cranial suture biology is very complex, but evidence suggests that the dura mater provides the biomolecular blueprints (e.g. the soluble growth factors), which guide the fate of the pleuripotent osteogenic fronts. While our knowledge of these dura-derived signals has increased dramatically in the last decade, we have barely begun to understand the fundamental mechanisms that mediate cranial suture fusion or patency. Interestingly, recent advances in both premature human and programmed murine suture fusion have revealed unexpected results, and have generated more questions than answers.

Craneosinostesis: consideraciones sobre su patogenia / Craneosynostesis: considerations on its pathogenecity

La craneosinostosis -entidad producida por el cierre precoz de las suturas craneales- se conoce desde la antigüedad; su patogenia constituye uno de los temas más polémicos desde el siglo pasado y son múltiples los mecanismos propuestos. Luego de una amplia revisión de la literatura médica los autores del trabajo reúnen las teorías en 5 grupos: defecto primario de la bóveda, intraútero, defecto primario de la base, alteración primaria del mesénquima y hereditaria. Se emiten consideraciones según la propia experiencia práctica y se plantea que de todas las hipótesis analizadas existen 2 fundamentales: la teoría de Moss, que se refiere a un defecto primario de la base y la de Park y Powers, que sugiere una alteración primaria del mesénquima

Craneo en "hoja de trébol": presentación de tres pacientes / Cloverleaf skull: presentation of three cases

Se describen tres pacientes que presentaron cráneo en forma de "hoja de trébol". El primero asociado a enanismo tanatofórico, el segundo como una anomalía aislada y un tercero asociado a fisuras faciales. Los tres pacientes ilustran una notable diversidad de las manifestacines clínicas encontradas en esta entidad. Se describen los hallazgos por ultrasonografía, tomografía azial computarizada a nivel del sistema nervioso central. Se hace énfasis en el asesoramiento genético

Alteraciones orbitarias debidas a craneoestenosis prematu / Orbital alterations caused by premature craneal synostosis

Se presentan los cambios o alteraciones orbitarias debidas a sinostosis craneal prematura, principalmente pore escafocefalia, oxicefalia y plagiocefalia. Estos cambios se valoraron en cráneos que forman parte del acervo cultural de la Dirección de Antropología Física del Instituto Nacional de Antropología e Historia. Además se presenta un cráneo que presenta Leontiasis ósea o Hipertrosis generalizada.

Craneosinostosis: estudio de 50 casos en el Hospital del Niño / Craniosynostosis: study of 50 cases at the Child Hospital

Se estudia la casuística del Servicio de Neurocirugía del Hospital del Niño en el periodo comprendido entre julio de 1974 a junio 1984. Se concluye que el sexo masculino es más frecuentemente afectado; el 76 por ciento es visto por el especialista antes del 1er año de vida. Hay una asociacón apreciable entre prematuridad y craneosinostosis sin poderse afirmar que sea una relación de causa a efecto, ni viceversa. La edad de la madre parece no jugar algún rol en la etiopatogenia, las manifestaciones clínicas más frecuentes de esta entidad son las de formación craneal, las convulsiones y el retardo psicomotor; la forma clínica más frecuente es la acrocefalia, el 20 por ciento de los casos se asocia a anomalías de otros órganos. A 8 meses de observación el revestimiento de los bordes de la craniectomía en dos casos con duramadre homóloga parace prometedor