Qualitative Assessment of Surgical Repair of Three Types of Unilateral Cleft Lip

Abstract Objective: To assess the effect of the three types of unilateral cleft lip (UCL) [cleft lip only, cleft lip and alveolus, and cleft lip alveolus and palate] on the outcome of the repair. Material and Methods: This study was a case series of effect of types of UCL on the outcome of the repair. Fifteen subjects each were in three UCL phenotypes groups. Evaluation of the scar, lip, and nose was done qualitatively by both parents/guardians and professionals using a modified form of the criteria described by Christofides et al. (2006). Results: In the assessment of the surgical scar, the parents found a difference between the three types of cleft in terms of texture, shape, and width of the scar and presence of columella deviation. The professional assessors, however, only found the three types of cleft to be different in the presence of alar flattening. Conclusion: Differences truly exist in the outcome of surgical repair of the three types of unilateral cleft lip, especially in the aesthetics of the nose and in the width and shape of the residual lip scar. Thus, it is important to consider this in the assessment of UCL repair because putting the subtypes together might have a negative impact on the assessment.

Cancer diagnostic profile in children with structural birth defects: An assessment in 15,000 childhood cancer cases.

BACKGROUND: Birth defects are established risk factors for childhood cancer. Nonetheless, cancer epidemiology in children with birth defects is not well characterized. METHODS: Using data from population-based registries in 4 US states, this study compared children with cancer but no birth defects (n = 13,111) with children with cancer and 1 or more nonsyndromic birth defects (n = 1616). The objective was to evaluate cancer diagnostic characteristics, including tumor type, age at diagnosis, and stage at diagnosis. RESULTS: Compared with the general population of children with cancer, children with birth defects were diagnosed with more embryonal tumors (26.6% vs 18.7%; q < 0.001), including neuroblastoma (12.5% vs 8.2%; q < 0.001) and hepatoblastoma (5.0% vs 1.3%; q < 0.001), but fewer hematologic malignancies, including acute lymphoblastic leukemia (12.4% vs 24.4%; q < 0.001). In age-stratified analyses, differences in tumor type were evident among children younger than 1 year and children 1 to 4 years old, but they were attenuated among children 5 years of age or older. The age at diagnosis was younger in children with birth defects for most cancers, including leukemia, lymphoma, astrocytoma, medulloblastoma, ependymoma, embryonal tumors, and germ cell tumors (all q < 0.05). CONCLUSIONS: The results indicate possible etiologic heterogeneity in children with birth defects, have implications for future surveillance efforts, and raise the possibility of differential cancer ascertainment in children with birth defects. LAY SUMMARY: Scientific studies suggest that children with birth defects are at increased risk for cancer. However, these studies have not been able to determine whether important tumor characteristics, such as the type of tumor diagnosed, the age at which the tumor is diagnosed, and the degree to which the tumor has spread at the time of diagnosis, are different for children with birth defects and children without birth defects. This study attempts to answer these important questions. By doing so, it may help scientists and physicians to understand the causes of cancer in children with birth defects and diagnose cancer at earlier stages when it is more treatable.

No. 365-Fetal and Perinatal Autopsy in Prenatally Diagnosed Fetal Abnormalities with Normal Chromosome Analysis.

OBJECTIVE: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of non-chromosomal anomalies in order to assist health care providers in providing postnatal counselling regarding diagnosis and potential recurrence risks. OUTCOMES: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2010, 2011, and 2017, using appropriate key words (fetal autopsy postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also highlights the need for a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated. The authors recognize that there is variability across Canada in access to the cited services and resources. As such, these recommendations were developed in an attempt to promote access and to provide a minimum standard for all provinces and territories across the country. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).

Assessment of genomic instability and proliferation index in cultured lymphocytes of patients with Down syndrome, congenital anomalies and aplastic anaemia.

One hundred and fifteen cases [Down Syndrome (DS) n = 75, Multiple Congenital Anomalies (MCA) n = 15 and Aplastic Anaemia (AA) n = 25], with respect to their nature of predisposition to cancer, were selected for clinical, cytogenetic and cyto-molecular studies to understand the severity of genomic instability according to the nature of the different diseases. Cytogenetic studies included chromosomal aberration (CA) assays and cytokinesis block micronucleus cytome (CBMN-Cyt) assays. In DS, MCA and AA, average frequencies of nuclear anomalies (NA) were 0.015 ±â€¯0.0006, 0.021 ±â€¯0.00123, 0.031 ±â€¯0.00098, respectively and CA were 0.107 ±â€¯0.003, 0.105 ±â€¯0.008, 0.158 ±â€¯0.006, respectively per metaphase. The extent of genomic instability in patients analysed by CBMN-Cyt assays and CA assays was statistically significant in all groups. Comparatively decreased cytokinesis block proliferation index (CBPI) observed in AA patients of 1.59 ±â€¯0.05, support the assumption that decreased levels of CBPI indicate increased genomic damage. Furthermore, we performed peptide nucleic acid fluorescence in situ hybridisation (PNA FISH) analysis to understand the mechanisms behind genomic instability and telomere dysfunction. PNA FISH showed increased frequencies of telomere signal free ends (0.98 ±â€¯0.13) in individuals with higher genomic instability. Therefore, the results demonstrate that increased chromosomal instability along with higher telomere attrition or loss may initiate gross DNA damage and leads to chromosomal instability, which is an important mechanism for triggering genomic instability - an important hallmark of cancer cells.

Dysmorphologic assessment in 115 Mayer-Rokitansky-Küster-Hauser patients.

Mayer-Rokitansky-Küster-Hauser (MRKH) patients are characterized by congenital aplasia of the uterus and the upper part of the vagina, with normal secondary sexual characteristics. This disorders affects one in 4000-5000 females and it is classified as typical, type I or isolated, and as atypical, type II, manifesting additional malformations. To date, no specific study has addressed the question of facial features in MRKH patients. The aim of this study is to perform a dysmorphological assessment of a large cohort of patients. We studied 115 women referred to our center from 2008 to 2012. Seventy-two percentage (83/115) of our patients showed isolated uterovaginal aplasia (MRKH type I); 32/115 (28%) had other abnormalities including kidney and cardiac defects, skeletal anomalies, and hearing impairment. Auxologic investigations comprised measurements of height, weight, BMI, head circumference, arm span, span to height ratio, hand length, middle finger length, foot length, inner and outer intercanthal distance, and auricle length. All patients had normal measurements, except for the outer canthal distance-inner canthal distance ratio, which was consistent with elongated eyelids. Women with MRKH syndromes do not present a typical facial feature and a dysmorphological examination of all patients seems unnecessary. However, a multidisciplinary approach is useful with respect to explaining the etiology, interpreting test results, and counseling.

The rectovaginal septum: visible on magnetic resonance images of women with Mayer-Rokitansky-Küster-Hauser syndrome (Müllerian agenesis).

INTRODUCTION AND HYPOTHESIS: Ongoing debate exists about whether the rectovaginal septum (Denonvilliers' fascia) is myth or reality. This study evaluates magnetic resonance images (MRI) of women with Müllerian agenesis for the presence of fascial layers between the rectum and the bladder to test the hypothesis that this layer exists in the absence of the vagina. METHODS: This is a secondary analysis of a study describing MRI aspects in women with vaginal agenesis before and after laparoscopic Vecchietti procedure. Study participants (n =16) had a multiplanar pelvic MR scan. Images were evaluated independently by two investigators (MH, JOLD) for the appearance of layers separate from the bladder and rectum in the area of interest, with characteristic anatomical features of the septum. RESULTS: Participants' mean age was 19.4±2.6 years ± standard deviation (SD). In 12 of 16 patients (75 %) a distinct layer between rectum and bladder was identified in either the axial(4/16; 25 %) or sagittal (12/16; 75 %) scan or both. Characteristic anatomical features included lateral attachment to the levator ani muscle, cranial fusion to the cul-de-sac peritoneum,and caudal insertion into the perineal body.Conclusions Three quarters of women with Müllerian agenesis have a visible layer between bladder and rectum. As none of the participants had a vagina, these results support the existence of a rectovaginal septum, separate from a vaginal adventitia.

Assessment of gross fetal malformations: the modernized Wilson technique and skeletal staining.

Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents, such as rabbits, rats, and mice, have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. Although many years have passed since Wilson created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemicals used in the experiments and also the analysis of the experimental data. While only minor modifications have been made to this protocol since its beginning, major advances have been made in the dissemination of teratology information to the public such that information is now available through the Internet--information including the identification of an increasing number of teratogens and the understanding of the pathogenesis as it relates to the etiology of birth defects. Despite these advances, however, there has been little decrease in the overall incidence of major birth defects, although significantly improved reporting and ascertainment of birth defects must be factored into the equation in determining birth defect rates. Future birth defect prevention may be based on the understanding of individual genomes and pharmacogenomics, and as the interaction between teratogenic and genetic factors is better understood--with the hope that the incidence of both chemically induced and genetic defects will one day be substantially reduced.

Identification of specific malformations of sea urchin larvae for toxicity assessment: application to marine pisciculture effluents.

Standard toxicity screening tests are useful tools in the management of impacted coastal ecosystems. To our knowledge, this is the first time that the sea urchin embryo development test has been used to evaluate the potential impact of effluents from land-based aquaculture farms in coastal areas. The toxicity of effluents from 8 land-based turbot farms was determined by calculating the percentage of abnormal larvae, according to two criteria: (a) standard, considering as normal pyramid-shaped larvae with differentiated components, and (b) skeletal, a new criterion that considers detailed skeletal characteristics. The skeletal criterion appeared to be more sensitive and enabled calculation of effective concentrations EC(5), EC(10), EC(20) and EC(50), unlike the classical criterion. Inclusion of the skeleton criterion in the sea urchin embryo development test may be useful for categorizing the relatively low toxicity of discharges from land-based marine fish farms. Further studies are encouraged to establish any causative relationships between pollutants and specific larval deformities.

Fetal and perinatal autopsy in prenatally diagnosed fetal abnormalities with normal karyotype.

OBJECTIVE: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of non-chromosomal malformations, and to assist clinicians in providing postnatal counselling regarding fetal diagnosis and recurrence risks. OUTCOMES: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 and 2010, using appropriate key words (fetal autopsy, postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also provides a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Recommendations 1. Standard autopsy should ideally be an essential part of fully investigating fetal loss, stillbirths, and neonatal deaths associated with non-chromosomal fetal malformations. (II-3A) 2. Clinicians and health care providers approaching parents for autopsy consent should discuss the options for a full, limited, or step-wise postmortem examination; the issue of retained fetal tissues; and the value of autopsy and the possibility that the information gained may not benefit them but may be of benefit to others. This information should be provided while respecting the personal and cultural values of the families. (III-A) 3. If parents are unwilling to give consent for a full autopsy, alternatives to full autopsy that provide additional clinical information must be presented in a manner that includes disclosure of limitations. (III-A) 4. External physical examination, medical photographs, and standard radiographic or computed tomography should be offered in all cases of fetal anomaly(ies) of non-chromosomal etiology. (II-2A) 5. Well-designed, large prospective studies are needed to evaluate the accuracy of postmortem magnetic resonance imaging. It cannot function as a substitute for standard full autopsy. (III-A) 6. The fetal and perinatal autopsies should be performed by trained perinatal or pediatric pathologists. (II-2A) 7. The need for additional sampling is guided by the results of previous prenatal and/or genetic investigations, as well as the type of anomalies identified in the fetus. Fibroblast cultures may allow future laboratory studies, particularly in the absence of previous karyotyping or if a biochemical disorder is suspected, and DNA analysis. (II-3A) 8. In cases requiring special evaluation, the most responsible health care provider should have direct communication with the fetopathologist to ensure that all necessary sampling is performed in a timely manner. (II-3A) 9. The most responsible health care providers must see the families in follow-up to share autopsy findings, plan for the management of future pregnancies, obtain consent for additional testing, and offer genetic counselling to other family members when appropriate. (III-A).

Detailed assessment of the ear in Cornelia de Lange syndrome: comparison with a control sample using the new dysmorphology guidelines.

The literature abounds with reports of malformation syndromes in which human external ears are variously described as dysplastic, abnormal, large/small, low set, typical, or in some way unusual. Rarely is the ear well illustrated or described in meaningful detail. With few exceptions, such as Down syndrome, there is no real understanding of the degree to which ear morphology is affected in a specific syndrome. This paper describes a retrospective attempt to apply the recently published Morphological Definitions of the ear to compare a control sample of convenience with a group of patients with Cornelia de Lange syndrome (CdLS) (all six papers in this issue are available online, open access at http://www3.interscience.wiley.com/journal/121641055/issue). Although this study has a number of limitations, it demonstrates that the method can be successfully applied and is capable of producing data that can be subjected to statistical analysis. The ears of the patients with CdLS were significantly different from the controls over a number of descriptors, the most significant of which included more frequent apparent posterior rotation, a shorter more serpiginous antihelical stem and sharper antihelical to inferior crus angle, a shorter crus helix, a more V-shaped incisura, and a smaller lobe.

Case series of 148 tongue-tied newborn babies evaluated with the assessment tool for lingual frenulum function.

OBJECTIVE: the Assessment Tool for Lingual Frenulum Function (ATLFF) is the only available tool designed to assess newborn babies for the severity of tongue-tie. The aim of this study was to describe the ATLFF scores obtained on a series of 148 tongue-tied newborn babies. DESIGN: prospective case series. SETTING: a 420-bed community hospital in St. Paul, Minnesota, USA. PARTICIPANTS: newborn babies admitted to the normal newborn nursery from October 1, 2000 to May 1 2002. MEASUREMENTS AND FINDINGS: all babies in the nursery were examined for tongue-tie. One-hundred and forty-eight tongue-tied babies were examined using the ATLFF by at least one of three examiners. The ATLFF could not be completed on five babies. Of the remaining babies, 40 (28%) received 'perfect' scores, five (3.5%) received 'acceptable' scores, and 19 (13.3%) received 'function impaired' scores. The remaining 79 (55.2%) babies received scores that did not fall into any of the three categories of scores. The inter-rater agreement on whether or not the baby had a score of 'function impaired' on the ATLFF was moderate (kappa=0.44). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: few tongue-tied babies had a score of 'function impaired' on the ATLFF. It is a major limitation of the ATLFF that it does not classify most babies. The development and testing of a useful tool to determine which tongue-tied babies will have difficulty with breast feeding remains a research priority.

Radiation-free quantitative assessment of scoliosis: a multi center prospective study.

Accurate quantitative measurements of the spine are essential for deformity diagnosis and assessment of curve progression. There is much concern related to the multiple exposures to ionizing radiation associated with the Cobb method of radiographic measurement, currently the standard procedure for diagnosis and follow-up of the progression of scoliosis. In addition, the Cobb method relies on 2-D analysis of a 3-D deformity. The aim of this prospective study was to investigate the clinical value of Ortelius800 that provides a radiation-free method for scoliosis assessment in three planes (coronal, sagittal, apical), with simultaneous automatic calculation of the Cobb angle in both coronal and sagittal views. Analysis of the clinical value of the device for assessing spinal deformities was performed on patients with adolescent idiopathic scoliosis, deformity angles ranging from 10 degrees to 48 degrees. Correlation between Cobb angles measured manually on standard erect posteroanterior radiographs and those calculated by Ortelius800 showed an absolute difference between the measurements to be significantly less than +/- 5 degrees for coronal measurements and significantly less than +/- 6 degrees for sagittal measurements indicating good correlation between the two methods. The measurements from four independent sites and six independent examiners were not significantly different. We found the novel clinical tool to be reliable for following mild and moderate idiopathic curves in both coronal and sagittal planes, without exposing the patient to ionizing radiation. Considering the need for further validation of this new method, any change in treatment protocol should still be based on radiographic control.

Interruption of the inferior vena cava with azygos/hemiazygos continuation accompanied by distinct renal vein anomalies: MRA and CT assessment.

We report a case of interruption of the inferior vena cava with azygos/hemiazygos continuation and additional variations of the renal veins, an uncommon developmental anomaly. Magnetic resonance angiography and computed tomography, in association with clinical awareness, can be used to diagnose this entity.

Assessment of soft tissue facial asymmetry in medically normal and syndrome-affected individuals by analysis of landmarks and measurements.

We investigated soft tissue facial asymmetry in normal and syndrome-affected individuals ranging in age from 1 year to adulthood. The purposes of our study were to determine if facial asymmetry was greater in syndrome-affected individuals than in normal individuals and, if true, to distinguish those measurements that could be used in routine screening to identify the presence of syndromes in uncertain patients and, lastly, to investigate the causes of measurement asymmetry at the level of the landmarks. The last purpose was possible because we used a stereophotogrammetric method with which the three-dimensional (3D) landmark positions were obtained. In the statistically significantly different measurements, those from the right side were dominant, with one exception in each group, except normal males. In all groups the landmark analyses demonstrated the same trends, and while there was far less patterning in the 3D coordinates, these results were also consistent between the four groups. We compared the statistical findings of the 3D coordinates and measurements and found that there was no predictable relationship between significant findings in the landmarks and the measurements. In particular, we noted that statistical differences in measurements did not infer significant differences in the positions of the landmarks between the right and left sides of the face. Both the normal and syndrome-affected groups appeared to be equally canalized and similarly affected by developmental noise: When the bilateral measurement differences of each syndrome-affected subject were compared to the limits of normal asymmetry, less than 10% of the comparisons exceeded the norms.