Congenital malformations and minor anomalies in newborns depending on the type of resolved infertility and health of the parents

Introduction. The use of sisted reproductive technologies has had sufficient experience to reduce the risks associated with the technologies themselves. But pediatricians remain concerned about the health of children born from induced pregnancies because of the influence of the parents’ initial health on perinatal outcomes. Congenital malformations remain socially significant, the risk of which may be higher for children from induced pregnancy.Objective: to evaluate the effect of initial parental health and the methods of assisted reproductive technology used on the formation of congenital malformations and minor anomalies in children from singleton induced pregnancies.Materials and Methods. A retrospective cohort study was conducted using data on live-born children from singleton induced pregnancy born at the Avicenna Medical Center (Novosibirsk) over the period from 2007 to 2017 (n = 409). The reproductive, somatic, and infectious history of the parents and the methods of assisted reproductive technology used were assessed. Parental fertility treatment up to childbirth was performed in the same center, which ensured complete continuity of follow-up. Differences between the groups of children from SIP with and without congenital anomalies were determined using Pearson’s chi-squared test.Results and discussion. We found that children with congenital malformations and minor anomalies were more often born as a result of subsequent pregnancies; thawed embryos transferred at the blastocyst stage were used in assisted reproductive technology programs (p < 0.05); exacerbations of herpes type 2 infection were diagnosed during the current pregnancy (p < 0.05). In the group of children with only CM, the parents had a longer history of infertility (8.3 ± 1.2) years; pregnancy was achieved by transferring fresh embryos at the blastocyst stage (in 68.2% of cases). In the group of children without congenital malformations and minor anomalies, the maternal infectious history was more severe: there were significantly more frequent cases of urogenital infections (p < 0.05) and exacerbations of herpes simplex virus type 1 during pregnancy (p < 0.05).Conclusion. A set of measures aimed at an earlier solution of the infertility problem is necessary for the primary prevention of congenital abnormalities associated with the age and duration of parental infertility.

Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum

Cornelia de Lange syndrome (CdLS) is a genetic disease that exemplifies the evolution of knowledge in the field of rare genetic disorders. Originally described as a unique pattern of major and minor anomalies, over time this syndrome has been shown to be characterized by a significant variability of clinical expression. By increasing the number of patients described, knowledge of the natural history of the condition has been enriched with the demonstration of the relative frequency of various potential comorbidities. Since 2006, the discovery of CdLS’s molecular basis has shown an equally vast genetic heterogeneity linked to the presence of variants in genes encoding for the cohesin complex pathway. The most recent clinical-genetic data led to the classification of the “original syndrome” into a “clinical spectrum” that foresees the presence of classic patients, of non-classic forms, and of conditions that show a modest phenotypic overlapping with the original disease. Finally, the knowledge of the molecular basis of the disease has allowed the development of basic research projects that could lay the foundations for the development of possible innovative pharmacological treatments.

Deletion of 16q22.2q23.3 in a Boy with a Phenotype Reminiscent of Silver-Russell Syndrome

A 15-month-old boy presented with growth and global developmental delay, feeding difficulties, sleep disturbance and several minor anomalies, including a large anterior fontanel, relative macrocephaly, and a triangular face. Clinical suspicion prompted genetic investigations for Silver-Russell syndrome and related disorders. SNP array analysis led to the diagnosis of an approximately 10-Mb large deletion of the long arm in chromosome 16q22.2q23.3. Interstitial deletions of 16q show a wide variability of related features; however, considering the differences in size and location of the deletions in the known patients, the phenotypic overlap is surprising. Here, we report a novel microdeletion, compare the proband with data from scientific literature and international databases, and discuss possible diagnostic implications.

Xp11.2 Duplication in Females: Unique Features of a Rare Copy Number Variation

Among the diseases with X-linked inheritance and intellectual disability, duplication of the Xp11.23p11.22 region is indeed a rare phenomenon, with less than 90 cases known in the literature. Most of them have been recognized with the routine application of array techniques, as these copy number variations (CNVs) are highly variable in size, occurring in recurrent and non-recurrent forms. Its pathogenic role is not debated anymore, but the information available about the pathomechanism, especially in affected females, is still very limited. It has been observed that the phenotype in females varies from normal to severe, which does not correlate with the size of the duplication or the genes involved, and which makes it very difficult to give an individual prognosis. Among the patients studied by the authors because of intellectual disability, epilepsy, and minor anomalies, overlapping duplications affecting the Xp11.23p11.22 region were detected in three females. Based on our detailed phenotype analysis, we concluded that Xp11.23p11.22 duplication is a neurodevelopmental disorder.

The Risk of Chromosomal Abnormalities in Cases of Minor and Major Fetal Anomalies in the Second Trimester

Currently, noninvasive intrauterine screening for most chromosome abnormalities is available, but ultrasound examinations also play an important role during pregnancy, by drawing the attention to the suspect of a possible abnormality. Fetal ultrasound disorders can be classified into two major groups: (1) Major abnormalities are actually diagnosed malformations that are often associated with certain chromosome abnormalities but may be associated with other disorders (multiplex malformation) and may occur as isolated disorders (e.g., cardiac disorders, duodenal atresia, omphalocele, cystic hygroma (CH)). (2) Minor anomalies (“soft markers”) are not abnormal in themselves but are mild abnormalities that may occur in normal pregnancy but also increase the risk of certain chromosome aberrations. The minor anomalies in the second trimester include thickened nuchal fold (NF), mild ventriculomegaly, pyelectasis, hyperechogenic bowels, hyperechogenic papillary muscle, and shorter long bones. Plexus choroid cyst which is classified as a minor marker does not increase the risk of Down syndrome but increases the risk of trisomy 18 (Edwards syndrome). We want to emphasize the importance of screening of minor and major ultrasound abnormalities in detecting chromosomal abnormalities in the second trimester.

A STUDY ON SPECTRUM OF CONGENITALANOMALIES DELIVERED IN A TERTIARY CARE CENTER

INTRODUCTION: Congenital anomaliesaccount for 9% of neonatal deaths in India. Prevalence of birth anomalies in India is 6-7%. AIMS AND OBJECTIVES: The objective was to determine proportion and clinical spectrum of congenital anomalies and maternal and perinatal risk factors associated with congenital anomalies in live newborns in our area. MATERIALS AND METHODS: Neonates born in ALLURI SITARAMA RAJU ACADEMY OF MEDICAL SCIENCES hospital during study period with documented congenital anomalies are included. All still-borns and gestational age <22wks & birth weight <400gm were excluded. Retrospective hospital-based study, conducted between January 2019 to December 2019 in ASRAM Hospital. RESULTS: The total number of births is 1132 during this one year of which, 106 newborns had congenital anomalies. In this study we found that major anomalies (80.2%) , Minor anomalies (19.8%).In this study we found that most of the anomalies were major and mostly involved cardiovascular system. In minor anomalies the most common defect was sacral dimple. CONCLUSION: Congenital anomalies can be reduced with in-utero surgeries, and necessary preventive measures which are becoming feasible.

TRANSLATION, CULTURAL ADAPTATION, AND EVIDENCE OF INSTRUMENT VALIDITY FOR A MORPHOLOGICAL EXAMINATION PERFORMED IN CHILDREN WITH AUTISM SPECTRUM DISORDER

ABSTRACT Objective: For every 100 random children diagnosed with autism, at least 20 have morphological abnormalities, often associated with syndromes. Brazil does not have a standardized and validated instrument for morphological physical examination. This study aimed to translate into Brazilian Portuguese and culturally adapt the clinical signs described in the Autism Dysmorphology Measure, as well as validate the instrument in a sample of children with autism. Methods: The original instrument was translated, culturally adapted, and published in full, following traditional procedures for translation, back-translation, and terminology adaptation according to the Nomina Anatomica. The sample included 62 children from a published multicenter study, with intelligence quotient between 50–69, of both genders, with chronological age between 3–6 years. Two clinical geneticists performed the morphological physical examination, which consisted of investigating 82 characteristics assessing 12 body areas. We used Cohen’s Kappa coefficient to evaluate the agreement between the two observers. Results: The final version of the instrument – translated into Brazilian Portuguese and culturally adapted – showed high agreement between the two observers. Conclusions: The translated instrument meets all international criteria, and minor anomalies and their clinical descriptions were standardized and are recognizable for physicians not specialized in genetics.

The Clinical and Functional Description of the Cardiovascular System in Children with Diseases of the Circulatory System

Objective: to give the clinical and functional characteristics of the cardiovascular system in children with diseases of the circulatory system. Material and мethods. The study involved 188 children aged 8-16 with different cardiovascular diseases (CVD) examined at the Cardiology Ward of Gomel Regional Children`s Hospital. Depending on the profile of their diseases, the children were divided into five main groups: group 1 - children with minor anomalies of heart development, group 2 - children with congenital heart diseases, group 3 - children with rhythm disorders, group 4 - children with autonomic dysfunction, group 5 - children with arterial hypertension. Along with the clinical examination the children were performed an electrocardiogram (ECG) and underwent Holter monitoring (HM). Results. The polymorphism of complaints was typical of the children of all the groups, according to the ECG data, conduction disturbances were the most common in the children of the first and second groups, and excitability disorders were typical of the children of the third group. Normal ECG was most often recorded in the children of the fourth and fifth groups. By the НM data arrhythmia (II Lown class and higher) was most frequently detected in the children of the first and third groups, arrhythmia of V class prevailed in the second group of the children. Conclusion. The cardiologic examination found that the children with CVD had various complaints and different arrhythmia classes, while the ECG of the majority of the children with autonomic dysfunction and hypertension detected mild arrhythmias, which is indicative of prognostically favorable disease outcomes. Clinically significant arrhythmias were revealed most frequently in the children with minor anomalies of heart development, cardiac rhythm disorders and congenital heart diseases.