Improvement of quality of life on breast cancer-related lymphedema patients through a postmastectomy care program in Mexico: a prospective study.

PURPOSE: To assess whether health-related quality of life (HRQOL) improved through a postmastectomy care program focused on breast cancer-related lymphedema (BCRL) protection/awareness. METHODS: Postoperative breast cancer patients were enrolled prospectively (February-2018 to September-2019) at Nursing and Obstetrics Faculty, Durango, Mexico. Sociodemographic/clinical characteristics, arm measurements, and HRQOL evaluation with Functional Assessment Cancer Therapy-Breast Cancer were collected at baseline and after six follow-up assessments between six-to-twelve-month postmastectomy. Lymphedema was verified through circometry. Descriptive analysis and McNemar-Bowker test were used to evaluate paired differences in HRQOL. Subgroup analysis was conducted to assess sociodemographic/clinical characteristics of BCRL using Pearson's chi-squared or Fisher exact test along with odds ratios (OR) and 95% confidence intervals (CI). All tests were two-sided with P-values < 0.05 considered statistically significant. RESULTS: One-hundred-two patients developed BCRL (incidence 66.2%, n = 154). All dimensions of HRQOL improved after the postmastectomy care program (P < 0.05). The subgroup analysis indicated that elementary academic degree (OR = 2.40, 95%CI: 1.01-5.69), laborer (OR = 9.85, 95%CI: 3.30-29.3), and total mastectomy (OR = 4.23, 95%CI: 1.20-14.9) were more associated with BCRL (P < 0.05). Conversely, high school academic degree (OR = 0.46, 95%CI: 0.22-0.94), married status (OR = 0.42, 95%CI: 0.21-0.86), housewife (OR = 0.27, 95%CI: 0.12-0.61), professional occupation (OR = 0.10, 95%CI: 0.01-0.64), and having no comorbidities (OR = 0.31, 95%CI: 0.15-0.63) were less associated with BCRL (P < 0.05). CONCLUSION: Although HRQOL improved through the postmastectomy care program, our findings suggest that lower education, working as a laborer, and total mastectomy may be more associated with BCRL. Continuing research may uncover liabilities among BCRL patients within limited-resources settings.

Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of the Second Case and Phenotypic Assessment.

Casamassima-Morton-Nance syndrome (CMNS) is a rare disorder characterized by spondylocostal dysostosis (SCD), anal atresia, and urogenital anomalies. We describe a fetus with CMNS associated with a limb-body wall defect (LBWD), the second such case in the literature. We compare the phenotypic differences with previously reported cases, including those with segmentation anomalies of the axial skeleton, body wall defects, or absent/abnormal genitalia, revealing the consistent presence of SCD in CMNS. However, as expected, a wide phenotypic spectrum emerges, providing useful observations for fetal/neonatal screening relevant to differential diagnoses. Advanced diagnostic methods using imaging and next-generation skeletal dysplasia multi-gene panels are advisable, as they enable timely, actionable, well-informed decisions for parental counseling, potential elective termination of pregnancy, and prenatal and/or postnatal care. Most reported cases do not mention the recurrence of these usually lethal anomalies.

Prevalence and Clinical Factors Associated With Pes Planus Among Children and Adults: A Population-Based Synthesis and Systematic Review.

Estimates of pes planus ("flatfoot") prevalence vary considerably across studies. Moreover, there is uncertainty over which factors are associated with the pes planus prevalence. We aimed to systematically review the prevalence and clinical factors associated with flatfoot among children and adults. We searched Web of Science, PubMed/MEDLINE, and Google Scholar databases reporting population-based flatfoot prevalence. Two reviewers independently extracted the data and assessed the qualities of the studies. Subgroup analysis was conducted to analyze the associated factors on flatfoot prevalence. Frequencies, odds ratios (OR), and 95% confidence intervals (CI) were performed using descriptive analysis and chi-square test accounting for heterogeneity. Any conflict in the data analysis was discussed by all the reviewers. Twelve studies including 2509 flatfoot cases were analyzed (overall prevalence 15.6%, n = 16,000). The subgroup analysis indicated that male gender (OR = 1.26, 95% CI: 1.15-1.37), age groups 3 to 5 years (OR = 2.02, 95% CI: 1.78-2.30) and 11 to 17 years (OR = 1.91, 95% CI: 1.64-2.22), Asian race (OR = 2.34, 95% CI: 2.10-2.60), and obesity (OR = 2.62, 95% CI: 2.06-3.32) were more associated with flatfoot (p < .001). Conversely, female gender (OR = 0.44, 95% CI: 0.40-0.48) and White race (OR = 0.52, 95% CI: 0.47-0.57) were less associated with flatfoot (p < .001). Our findings may be valuable for clinical/surgical settings, particularly, for those modifiable findings and targeted populations. However, we suggest that future studies estimating flatfoot should consider prospective/multicenter designs using a common screening methods in random samples populations.

Whole exome sequencing identifies multiple novel candidate genes in familial gastroschisis.

BACKGROUND: Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis. METHODS: We employed WES in two affected half-sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS-PhoRank and Ensembl-Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS-PhoRank) and functional properties (Ensembl-Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes. RESULTS: No single gene-disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63-linked ubiquitination, protein-containing complex assembly, and regulation of transcription DNA-templated. CONCLUSION: Considering the likely gene-disrupting prediction results and similar biological pattern of mechanisms, we propose a joint "multifactorial model" in gastroschisis pathogenesis.

A clinical-pathogenetic approach on associated anomalies and chromosomal defects supports novel candidate critical regions and genes for gastroschisis.

BACKGROUND: Gastroschisis has been assumed to have a low rate of syndromic and primary malformations. We aimed to systematically review and explore the frequency and type of malformations/chromosomal syndromes and to identify significant biological/genetic roles in gastroschisis. METHODS: Population-based, gastroschisis-associated anomalies/chromosomal defects published 1950-2018 (PubMed/MEDLINE) were independently searched by two reviewers. Associated anomalies/chromosomal defects and selected clinical characteristics were subdivided and pooled by race, system/region, isolated, and associated cases (descriptive analysis and chi-square test were performed). Critical regions/genes from representative chromosomal syndromes including an enrichment analysis using Gene Ontology Consortium/Panther Classification System databases were explored. Fisher's exact test with False Discovery Rate multiple test correction was performed. RESULTS: Sixty-eight articles and 18525 cases as a base were identified (prevalence of 17.9 and 3% for associated anomalies/chromosomal defects, respectively). There were 3596 associated anomalies, prevailing those cardiovascular (23.3%) and digestive (20.3%). Co-occurring anomalies were associated with male, female, American Indian, Caucasian, prenatally diagnosed, chromosomal defects, and mortality (P < 0.00001). Gene clusters on 21q22.11 and 21q22.3 (KRTAP), 18q21.33 (SERPINB), 18q22.1 (CDH7, CDH19), 13q12.3 (FLT1), 13q22.1 (KLF5), 13q22.3 (EDNRB), and 13q34 (COL4A1, COL4A2, F7, F10) were significantly related to biological processes: blood pressure regulation and/or vessel integrity, angiogenesis, coagulation, cell-cell and/or cell-matrix adhesion, dermis integrity, and wound healing (P < 0.05). CONCLUSIONS: Our findings suggest that gastroschisis may result from the interaction of several chromosomal regions in an additive manner as a pool of candidate genes were identified from critical regions supporting a role for vascular disruption, thrombosis, and mesodermal deficiency in the pathogenesis of gastroschisis.

Genetic variants conferring susceptibility to gastroschisis: a phenomenon restricted to the interaction with the environment?

BACKGROUND: Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies. METHODS: Genetic association studies of gastroschisis published 1980-2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP-gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity. RESULTS: Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher's exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis. CONCLUSIONS: Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene-gene or gene-environmental interactions are warranted for better understanding the etiology of gastroschisis.

Familial occurrence of gastroschisis: a population-based overview on recurrence risk, sex-dependent influence, and geographical distribution.

PURPOSE: There is uncertainty over whether familial recurrences in gastroschisis might be higher. Moreover, scant information is available regarding its sociodemographic features. We aim to explore the recurrence risk, sex-dependent influence, and geographical distribution of familial gastroschisis. METHODS: A systematic review of the literature and data extraction from population-based studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features from 11 studies were pooled including 862 probands as a base. A descriptive analysis and Chi-square test were performed. RESULTS: Twenty-four probands had a positive family history of gastroschisis including 49 affected family members, for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence was 4.3%. Sex-dependent influence analysis (n = 879, from three studies) evidenced an increased susceptibility to gastroschisis in males (2.5%) compared to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's exact test (P = 0.023). CONCLUSION: Our findings support a greater liability attributable to familial factors on gastroschisis along with significant information for family and prenatal counseling. We suggest that future studies should include for a more accurate account for both familial and environmental confounding factors to uncover relatives and environmental exposures that more limited family histories may have missed.

Evaluation of familial factors in a Mexican population-based setting with gastroschisis: Further evidence for an underlying genetic susceptibility.

PURPOSE: To evaluate the occurrence of gastroschisis attributable to familial factors in a Mexican population-based setting. METHODS: A descriptive study was performed among gastroschisis cases born from 2010 through 2016 at Tijuana General Hospital (Baja California, Mexico) to generate multigenerational pedigrees. RESULTS: There were 87 gastroschisis cases from 57,217 live births. Six probands (6.9%) had another affected family member. Two half-siblings, a set of monozygotic twins, a mother-and-daughter occurrence, a distant paternal cousin and a distant maternal uncle were identified. Sibling recurrence was 5.5%. From 174 males and 153 females studied (n=327, involving 180 nuclear families), sex-dependent influence analysis evidenced an increased susceptibility to gastroschisis in males (3.2%) compared to females (1.8%) with an overall of 2.5% adjusted for proband. CONCLUSIONS: Our results provide a greater liability attributable to familial factors on gastroschisis. In spite of the predominant sporadic occurrence, underlying genetic susceptibility and environmental influences point to a complex interplay between genes and environmental factors in gastroschisis. LEVEL OF EVIDENCE: Level IV.

Otofaciocervical syndrome and metachondromatosis in a girl: Presentation of a novel association and remarks on clinical variability of branchial-arch disorders.

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial, ear, branchial, and musculoskeletal anomalies, along with hearing loss and mild intellectual disability. Clinically, its distinction from branchiootorenal syndrome can be difficult. To date, the coexistence of OFCS and metachondromatosis has not been reported. Here, we describe a sporadic patient with both OFCS and metachondromatosis. This novel association prompts us to do some remarks on the clinical variability of branchial-arch disorders; in fact, our observations are consistent with the highly variable expressivity of OFCS and illustrate the need of a more accurate characterization of these branchial-arch disorders. In the meantime, involvement of clavicles, scapulae and shoulders remains a distinctive feature of OFCS.

Anomalías inusuales del arco branquial, dermoepidérmicas y del sistema nervioso en un neonato con el síndrome VACTERL-H / Unusual branchial arch, dermoepidermal and nervous system anomalies in a neonate with VACTERL-H syndrome

El síndrome VACTERL-H es un trastorno complejo de malformaciones congénitas que implica vértebras, ano, corazón, tráquea, esófago, riñones, extremidades (del inglés limbs) e hidrocefalia. Su etiología se ha identificado sólo en algunos pacientes debido, en gran medida, a su naturaleza esporádica, así como a su alto grado de heterogeneidad clínica. En este informe se presenta a un neonato con el síndrome VACTERL-H, al que se asocian anomalías inusuales del arco branquial, dermoepidérmicas y del sistema nervioso, que se comparan con las descritas en la bibliografía médica. Según nuestra experiencia, esta presentación no sólo amplía el conocimiento del espectro de anomalías que se puede presentar en el síndrome VACTERL-H, sino que también podría ser útil en la identificación de pacientes con este fenotipo heterogéneo.

VACTERL-H syndrome is a complex disorder of congenital malformations that implies vertebrae, anus, heart, trachea, esophagus, kidneys, limbs and hydrocephalus. Its etiology has been identified in a fraction of patients largely due to their sporadic nature and its high degree of clinical heterogeneity. This report presents a newborn with VACTERL-H syndrome, associated with unusual branchial arch, dermoepidermal and nervous system anomalies, which are compared with those described in the medical literature. Based on our experience, the presentation of this case not only expands the knowledge of the spectrum of anomalies that can occur in VACTERL-H syndrome, but also can be useful in identifying patients with this heterogeneous phenotype.