CASE REPORT: LETHAL MULTIPLE PTERYGIUM SYNDROME

We report a case of lethal multiple pterygium syndrome (LMPS). Intrauterine fetal demise was diagnosed at 31 weeks' estimated gestational age. Subsequent fetopsy established the diagnosis of LMPS. Macroscopic, microscopic, and radiographic findings in the case are discussed, and LMPS is reviewed.     

Relationship of Phenotype and Genotype in X-Linked Amelogenesis Imperfecta

X-linked amelogenesis imperfectas (AI) resulting from mutations in the amelogenin gene (AMELX) are phenotypically and genetically diverse. Amelogenin is the predominant matrix protein in developing enamel and is essential for normal enamel formation. To date, 12 allelic AMELX mutations have been described that purportedly result in markedly different expressed amelogenin protein products. We hypothesize that these AMELX gene mutations result in unique and functionally altered amelogenin proteins that are associated with distinct amelogenesis imperfecta phenotypes. The AMELX mutations and associated phenotypes fall generally into three categories. (1) Mutations (e.g., signal peptide mutations) causing a total of loss of amelogenin protein are associated with a primarily hypoplastic phenotype (though mineralization defects also can occur). (2) Missense mutations affecting the N-terminal region, especially those causing changes in the putative lectin-binding domain and TRAP (tyrosine rich amelogenin protein) region of the amelogenin molecule, result in a predominantly hypomineralization/hypomaturation AI phenotype with enamel that is discolored and has retained amelogenin. (3) Mutations causing loss of the amelogenin C terminus result in a phenotype characterized by hypoplasia. The consistent association of similar hypoplastic or hypomineralization/hypomaturation AI phenotypes with specific AMELX mutations may help identify distinct functional domains of the amelogenin molecule. The phenotype-genotype correlations in this study suggest there are important functional domains of the amelogenin molecule that are critical for the development of normal enamel structure, composition, and thickness.     

Wall Imaging for Unilateral Intracranial Vertebral Artery Hypoplasia with Three-dimensional High-isotropic Resolution Magnetic Resonance Images

Background:

There are few studies for evaluating wall characteristics of intracranial vertebral artery hypoplasia (VAH). The aim of this study was to determine wall characteristics of VAH with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA) images and differentiate between acquired atherosclerotic stenosis and VAH.

Methods:

Thirty patients with suspicious VAH by luminograms were retrospectively enrolled between January 2014 and February 2015. The patients were classified as “acquired atherosclerotic stenosis” or “VAH” based on 3D VISTA images. The wall characteristics of VAH were assessed to determine the presence of atherosclerotic lesions, and the patients were classified into two subgroups (VAH with atherosclerosis and VAH with normal wall). Wall characteristics of basilar arteries and vertebral arteries were also assessed. The clinical and wall characteristics were compared between the two groups.

Results:

Five of 30 patients with suspicious VAH were finally diagnosed as acquired atherosclerotic stenosis by 3D VISTA images. 25 patients were finally diagnosed as VAH including 16 (64.00%) patients with atherosclerosis and 9 (36.00%) patients with normal wall. In the 16 patients with atherosclerosis, plaque was found in 9 patients, slight wall thickening in 6 patients, and thrombus and wall thickening in 1 patient. Compared with VAH patients with normal wall, VAH patients with atherosclerosis showed atherosclerotic basilar arteries and dominant vertebral arteries more frequently (P = 0.000).

Conclusions:

Three-dimensional VISTA images enable differentiation between the acquired atherosclerotic stenosis and VAH. VAH was also prone to atherosclerotic processes.     

Chronic hyperoxia and the development of the carotid body

Preterm infants often experience hyperoxia while receiving supplemental oxygen. Prolonged exposure to hyperoxia during development is associated with pathologies such as bronchopulmonary dysplasia and retinopathy of prematurity. Over the last 25 years, however, experiments with animal models have revealed that moderate exposures to hyperoxia (e.g., 30–60% O₂ for days to weeks) can also have profound effects on the developing respiratory control system that may lead to hypoventilation and diminished responses to acute hypoxia. This plasticity, which is generally inducible only during critical periods of development, has a complex time course that includes both transient and permanent respiratory deficits. Although the molecular mechanisms of hyperoxia-induced plasticity are only beginning to be elucidated, it is clear that many of the respiratory effects are linked to abnormal morphological and functional development of the carotid body, the principal site of arterial O₂ chemoreception for respiratory control. Specifically, developmental hyperoxia reduces carotid body size, decreases the number of chemoafferent neurons, and (at least transiently) diminishes the O₂ sensitivity of individual carotid body glomus cells. Recent evidence suggests that hyperoxia may also directly or indirectly impact development of the central neural control of breathing. Collectively, these findings emphasize the vulnerability of the developing respiratory control system to environmental perturbations.     

Transverse Aortic Arch to Descending Aorta Ratio: A New Echocardiographic Parameter for Management of Coarctation of the Aorta in the Infant

Objective. The purpose of this study was to establish an objective criterion to help assess adequacy of the transverse arch in newborns with coarctation and thereby optimize preoperative surgical decision making. Methods. Echocardiograms of 47 patients <6 months of age who underwent coarctation repair from September 2005 to November 2008 and 47 age‐matched healthy infants were reviewed. The proximal and distal transverse aortic arch to descending aorta ratios (TAA : DAO ratio) were calculated from the end‐systolic proximal and distal transverse aortic arch diameters and diameter of the descending aorta at the diaphragm. Results. Both the proximal and distal TAA : DAO ratios were significantly lower in the study vs. control group (P= .001) and in patients who underwent patch reconstruction of the aorta vs. extended end‐to‐end anastomosis (P= .014; P= .015). All patients who underwent patch reconstruction had a proximal and/or distal TAA : DAO <0.65. A cutoff of 0.65 was derived based on our analyses and an algorithm was developed to guide decision making. Forty‐six out of 47 patients were free from reintervention. Conclusion. The TAA : DAO ratio appears to be an accurate parameter by which the adequacy of the transverse arch can be assessed preoperatively using the proposed algorithm, and thus help determine the type of surgical intervention and approach.     

双舌形皮瓣修复先天缺损型耳垂裂

目的 介绍一种修复先天性耳垂裂的新方法。方法 将耳垂裂隙局部形成的双舌形皮瓣旋转、瓦合，治疗先天缺损型耳垂裂。结果 本组6例患者，皮瓣均成活，耳垂外形良好，色泽自然，无并发症发生。结论利用双舌形皮瓣修复耳垂裂，手术操作简单，创伤小，效果好，是一种值得推广使用的方法。     

Pax3 mRNA is decreased in the hearts of rats with experimental diaphragmatic hernia

Rats with nitrofen-induced congenital diaphragmatic hernia (CDH) have heart hypoplasia and cardiovascular malformations. The mechanism of action of nitrofen involves changes in neural crest signaling. Pax3 function is required for cardiac neural crest cells to complete their migration to the developing heart. The aim of this study was to examine whether Pax3 expression is changed at two gestational endpoints in rat embryos or fetuses exposed to nitrofen. On day E9.5 of gestation, pregnant rats received either 100 mg of nitrofen (n=10) or vehicle alone (control, n=10). The fetuses were recovered on E15 or E21. Their hearts were dissected out and weighed. Pax3 mRNA expression was determined by real-time polymerase chain reaction. We used two-tailed Students t-tests to compare groups, with a threshold of significance of p<0.05. Compared with controls, nitrofen-exposed fetuses had heart hypoplasia in terms of heart/body weight ratio (0.62±0.10% vs. 0.77±0.17%, p<0.05). Pax3 mRNA expression in the heart was significantly decreased on E15 in nitrofen-treated embryos (32.94±17.11 U vs. 55.09±11.56 U, p<0.05), and it was still decreased, although not significantly, in the hearts of nitrofen-exposed fetuses recovered on E21 (15.67±5.56 U vs. 20.51±5.92 U, not significant). In conclusion, Pax3 is underexpressed in the hearts of nitrofen-exposed embryonal rats before the end of gestation. The mechanism of action of Pax3 should be further investigated because it could be one of the targets for future prenatal transplacental intervention.Paper presented at the XVIIth International Symposium of Pediatric Surgical Research, Liverpool, United Kingdom, 1–2 October, 2004.     

Ultrastructure of Dental Enamel afflicted with Hypoplasia: An Atomic Force Microscopic Study

The ultrastructure of the human tooth enamel from a patient diagnosed with hypoplasia (HYP) was investigated using atomic force microscopy (AFM) and compared with the surface of normal human tooth enamel. Hypoplasia is a hereditary defect of dental enamel in which the enamel is deficient in either quality or quantity. AFM results presented for the HYP tooth enamel clearly demonstrate that the apatite crystal morphology in hypoplasia tooth enamel is perturbed in the diseased state which could result from a defective synthesis of the extracellular matrix proteins, e.g., amelogenin, by the ameloblasts. HYP enamel consisting of loosely packed, very small grains does not present a tendency for association, as in the case of the normal healthy tooth. Indeed, the enamel surface affected by HYP is porous and is made of much smaller grains. In some samples, the HYP part of enamel surface appeared in the form of a point-defect, which we believe may be associated with the early stages of the HYP deformation.