Decoding 22q11.2: prenatal profiling and first-trimester risk assessment in Danish nationwide cohort.

OBJECTIVES: To examine the distribution of nuchal translucency thickness (NT), free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in pregnancies with a fetal 22q11.2 aberration. Furthermore, the performance of combined first-trimester screening (cFTS) and a new risk algorithm targeting 22q11.2 deletions in detecting affected pregnancies was evaluated. Finally, prenatal malformations and pregnancy outcome were assessed. METHODS: This was a nationwide registry-based cohort study of all pregnancies that underwent prenatal screening with a due date between January 2008 and December 2018 in Denmark. All cases with a fetal 22q11.2 deletion or duplication (hg19 chr22:18.9mio-25.0mio) diagnosed pre- or postnatally or following pregnancy loss or termination of pregnancy were retrieved from the Danish Cytogenetic Central Register and linked with pregnancy data from the Danish Fetal Medicine Database. Fetal and maternal characteristics, including cFTS results and pregnancy outcome, of pregnancies with any 22q11.2 deletion or duplication (LCR22-A to -H) and pregnancies with a classic deletion or duplication (LCR22-A to -D) diagnosed by chromosomal microarray were compared with those of a chromosomally normal reference group. A risk algorithm was developed for assessing patient-specific risks for classic 22q11.2 deletions based on NT, PAPP-A and ß-hCG. Detection rates and false-positive rates at different risk cut-offs were calculated. RESULTS: We included data on 143 pregnancies with a fetal 22q11.2 aberration, of which 97 were deletions (54 classic) and 46 were duplications (32 classic). NT was significantly increased in fetuses with a classic deletion (mean, 1.89 mm), those with any deletion (mean, 1.78 mm) and those with any duplication (mean, 1.86 mm) compared to the reference group (mean, 1.65 mm). ß-hCG multiples of the median (MoM) was decreased in all 22q11.2 subgroups compared with the reference group (mean, 1.02) and reached significance in pregnancies with a classic deletion and those with any deletion (mean, 0.77 and 0.71, respectively). PAPP-A MoM was significantly decreased in pregnancies with a classic duplication and those with any duplication (mean, 0.57 and 0.63, respectively), and was significantly increased in pregnancies with a classic deletion and those with any deletion (mean, 1.34 and 1.16, respectively), compared to reference pregnancies (mean, 1.01). The screen-positive rate by cFTS was significantly increased in pregnancies with a classic deletion (13.7%), any deletion (12.5%), a classic duplication (46.9%) or any duplication (37.8%) compared to the reference group (4.5%). A risk algorithm targeting classic 22q11.2 deletions more than doubled the prenatal detection rate of classic 22q11.2 deletions, but with a substantial increase in the false-positive rate. Structural malformations were detected in 41%, 35%, 17% and 25% of the pregnancies with a classic deletion, any deletion, classic duplication or any duplication, respectively. Pregnancy loss occurred in 40% of pregnancies with a classic deletion and 5% of those with a classic duplication diagnosed prenatally or following pregnancy loss. CONCLUSIONS: The distribution of cFTS markers in pregnancies with a classic 22q11.2 duplication resembles that of the common trisomies, with decreased levels of PAPP-A. However, classic 22q11.2 deletions are associated with increased levels of PAPP-A, which likely limits early prenatal detection using the current cFTS risk algorithm. The scope for improving early detection of classic 22q11.2 deletions using targeted risk algorithms based on NT, PAPP-A and ß-hCG is limited. This demonstrates the capability, but also the limitations, of cFTS markers in detecting atypical chromosomal anomalies, which is important knowledge when designing new prenatal screening programs. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Paternal age, risk of congenital anomalies, and birth outcomes: a population-based cohort study.

The objective of the study was to explore the impact of paternal age on the risk of congenital anomalies and birth outcomes in infants born in the USA between 2016 and 2021. This retrospective cohort study used data from the National Vital Statistics System (NVSS) database, a data set containing information on live birth in the USA between 2016 and 2021. Newborns were divided into four groups based on their paternal age (< 25, 25-34, 35-44, and > 44 years) and using the 25-34 age group as a reference. The primary outcomes were congenital anomalies involving structural anomalies and chromosome anomalies. Secondary outcomes were preterm birth, low birth weight, severe neonatal perinatal asphyxia, and admission to neonatal intensive care units (NICU). A multivariable logistic regression model was used to analyze the association between paternal age and outcomes. Overall, 17,764,695 live births were included in the final analyses. After adjusting confounding factors, advanced paternal age > 44 years was associated with increased odds of congenital anomalies (adjusted odds ratio (aOR) = 1.17, 95%CI 1.12-1.21) compared with the 25-34 age group, mainly for the chromosomal anomalies (aOR = 1.59, 95%CI 1.40-1.78) but not the structure anomalies (aOR = 1.03, 95%CI 0.97-1.09). The risk of preterm delivery, low birth weight, and NICU hospitalization in their infants was increased by advanced parental age as well.  Conclusion: Advanced paternal age increases the risk of congenital anomalies, especially chromosomal anomalies in their offspring, implying prenatal genetic counseling is required. What is Known: • There's a rising trend of advanced paternal age, which is associated with an increased likelihood of premature birth and low birth weight in their offspring. However, the exploration between paternal age and congenital abnormalities in offspring was limited and contradictory. What is New: • Infants with a paternal age > 44 years were more likely to be born with congenital anomalies, especially chromosomal anomalies.

Pulmonary vascular resistance and compliance in individuals with trisomy 18.

Individuals with trisomy 18 (T18) usually have congenital heart disease, often with pulmonary hypertension, which is associated with poor outcomes. This study aimed to explore the characteristics of pulmonary circulation including pulmonary vascular resistance (Rp) and compliance (Cp) among them. We retrospectively reviewed cardiac catheterization data in subjects with T18, trisomy 21 (T21), and without chromosomal anomaly (control group) who were referred due to heart failure associated with ventricular septal defect between 2000 and 2020. Pulmonary hemodynamic parameters including Rp and Cp were compared between these groups. We studied 20 subjects with T18, 88 subjects with T21, and 240 control subjects. There was no significant difference in age (T18: 4.6 [3.0-6. 9] vs. T21: 2.8 [1.9-4.0] vs. control: 2.9 [1.6-3.2] months, p = 0.06) and mean pulmonary arterial pressure (T18: 41 [33-49] vs. T21: 35 [30-41] vs. control: 36 [28-43] mmHg, p = 0.121) between the groups. The pulmonary to systemic blood flow ratio (Qp/Qs) (p = 0.983), Rp (p = 0.449), and Cp (p = 0.195) did not differ between T18 and control groups. However, Qp/Qs and Cp in T18 group were significantly greater than that in T21 group (T18: Qp/Qs: 3.4 [2.3-5.2] vs. T: 21 2.3 [1.7-3.7], p = 0.001. Cp: 3.5 [2.3-5.5] vs. 2.3 [1.6-3.1] mmHg/mL/m2 , p = 0.007), while Rp was identical between the groups (T18: 2.0 [1.6-3.3] vs. T21: 2.3 [1.7-3.7], p = 0.386). The pulmonary circulation in T18 subjects differed from that observed in T21 subjects, and identical to that observed in control subjects. Pulmonary hypertension is expected to be normalized after reasonable corrective surgery in T18 patients with congenital heart disease.

Relationship Between Pulmonary Arterial Resistance and Compliance in Patients with Down Syndrome.

This study aimed to clarify the characteristics of pulmonary arterial resistance (Rp)-compliance (Cp) coupling in individuals with Down syndrome (DS), who have increased risks of pulmonary arterial hypertension (PAH). We performed cardiac catheterization before and after corrective surgery in 85 DS infants and 85 controls with congenital heart disease and PAH. We retrospectively collected hemodynamic data and compared Rp and Cp between the groups. Age at surgery was 3.5 (2.6-4.6) months. The first and second catheterizations were performed 1 month before and after corrective surgery in both groups. Preoperative Cp in DS patients was significantly lower than that in controls [2.27 (1.62-3.0) vs. 2.50 (1.86-3.31) mL/mmHg/m2, p = 0.039], although there was no significant difference in mean pulmonary arterial pressure and Rp between the groups. Analysis of covariance revealed that the slopes of the preoperative regression lines for the logarithmic transformations of Rp and Cp were identical in DS patients and controls (p = 0.299). However, the postoperative regression line was shifted downward in DS patients after corrective surgery. Postoperative home oxygen therapy (HOT) was performed in 39 patients (36 DS patients) and multivariate logistic regression analysis revealed that postoperative HOT was significantly related to low preoperative Cp (p = 0.039) and DS (p = 0.0001). Individuals with DS have the unique pulmonary vasculature characterized with low Cp that is related to postoperative HOT.

Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters.

AIM: To examine the performance of the combined First Trimester Screening (cFTS) algorithm when outliers of 4 risk parameters (maternal age, nuchal translucency (NT) thickness, PAPP-A and ß-hCG) were included in the classification of "high-risk". METHODS: A retrospective analysis of singleton pregnancies undergoing cFTS between 2008 and 2011 in Denmark. Abnormal karyotypes were classified as trisomy 21 (T21), trisomy 13 (T13) and trisomy 18 (T18), sex chromosome aberrations and atypical abnormal karyotypes. RESULTS: cFTS was completed in 193,638 pregnancies. In 10,205 (5.3%) cases, cytogenetic or molecular analysis was performed pre- or postnatally. An abnormal karyotype was seen in 1,122 (11.0%). The algorithm identified 87% of T21, 80% of T13, 75% of T18, 79% of sex chromosome aberrations and 35% of atypical abnormal karyotypes. Additional classification of a single risk parameter outlier (low PAPP-A or free ß-hCG (< 0.2 MoMs), high ß-hCG (≥5.0 MoMs), maternal age ≥45 years or NT ≥3.5 mm) as being at high-risk would have improved detection rates to 88, 80, 81, 81 and 37% respectively. The screen positive rate increased from 4.4 to 4.8%. DISCUSSION: Addition of outliers of the 4 parameters used in cFTS algorithm will lead to a statistically significant increase in detection rates for chromosomal abnormality.

Cleidocranial Dysplasia with 6p21.1-p12.3 Microdeletion: A Case Report and Literature Review.

OBJECTIVE: The aim of this article is to publish a literature review and report on a new case of cleidocranial dysplasia syndrome with 6p21.1-p12.3 microdeletion. DESIGN: A PubMed search using "cleidocranial dysplasia syndrome (CCD)" or "6p microdeletion" was performed. Articles with information relevant to our case were obtained for review. A new case of cleidocranial dysplasia syndrome is presented to describe and discuss clinical manifestations, pathogenesis, clinical progression of cleidocranial dysplasia syndrome, and management. RESULTS: There were 22 articles with reports of cleidocranial dysplasia syndrome or 6p microdeletion. Cleidocranial dysplasia syndrome, a rare genetic disorder, documented to have an autosomal dominant inheritance pattern and caused by caused by mutations of the transcription factor RUNX2. RUNX2 has been mapped to chromosome 6p21. The anomalies in cleidocranial dysplasia syndrome can involve not only the clavicle and skull but the entire skeleton because the membranous as well as endochondral bone formation may be affected. Upon follow-up, our patient was found to have global developmental delay. CONCLUSIONS: We report a near-term neonate with characteristic features of cleidocranial dysplasia and a 6p21.1-p12.3 microdeletion. Cleidocranial dysplasia syndrome is a rare autosomal dominant skeletal dysplasia. The mutation of the RUNX2 gene results in cleidocranial dysplasia syndrome.

Rapidly progressive pulmonary veno-occlusive disease in an infant with Down syndrome.

A 4-month-old girl with Down syndrome showed unexpected deterioration of pulmonary hypertension. Despite aggressive pulmonary vasodilation therapy, the patient died at 5 months of age. Lung autopsy showed that the pulmonary veins were obliterated by intimal fibrous thickening, and the media of the veins was arterialised with an increase in elastic fibres. Pulmonary veno-occlusive disease should be considered in the management of individuals with Down syndrome.

Prenatal and Postnatal Survival of Fetal Tetralogy of Fallot: A Meta-analysis of Perinatal Outcomes and Associated Genetic Disorders.

OBJECTIVES: The aim of this systematic review was to compare the postnatal outcomes, genetic testing results, and sonographic findings in 3 subtypes of tetralogy of Fallot. METHODS: Thirty-six articles from the MEDLINE and EMBASE databases were selected for this review. The postnatal outcomes, karyotyping results, and sonographic findings of fetal tetralogy of Fallot with pulmonary stenosis, tetralogy of Fallot with pulmonary atresia, and tetralogy of Fallot with an absent pulmonary valve were collected and compared. RESULTS: The survival rates (termination of pregnancy was considered fetal death) for prenatally diagnosed tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve at the end of neonatal period were significantly lower than the rate for tetralogy of Fallot with pulmonary stenosis (P < .05). The survival rate for tetralogy of Fallot with pulmonary atresia was also lower at birth (P < .001). Major chromosomal anomalies were more frequently detected in tetralogy of Fallot with pulmonary stenosis (P< .05); conversely, 22q11 deletion was present more often in fetuses with tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve (P < .001). Compared to tetralogy of Fallot with pulmonary stenosis, a right aortic arch was more associated with tetralogy of Fallot with pulmonary atresia (32.6%; P < .05), and the ductus arteriosus was almost always absent in tetralogy of Fallot with an absent pulmonary valve (87.5%; P < .001). CONCLUSIONS: The postnatal outcomes, genetic testing results, and sonographic findings are different among subtypes of tetralogy of Fallot. Documenting those details at diagnosis can help specialists better counsel their patients.

7q21.11 Microdeletion in a Neonate With Goldenhar Syndrome: Case Report and a Literature Review.

The oculoauriculovertebral spectrum or Goldenhar syndrome is characterized by varying degrees of prevalently unilateral underdevelopment of the craniofacial structures (orbit, ear, and mandible) in association with vertebral, cardiac, renal, and central nervous system defects. We report on a term neonate with a partial monosomy 7q21.11 with marked hemifacial microsomia, facial clefting, and spinal anomaly. The estimated size of the monosomic region of 7q21.11 was approximately 55 kilobases. This is the first report of a patient with partial monosomy 7q21.11 associated with oculoauriculovertebral spectrum.

Congenital heart anomaly in newborns with congenital diaphragmatic hernia: a single-center experience.

OBJECTIVE: To evaluate the impact of the presence of a congenital heart anomaly (CHA) and its potential contribution to morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). METHODS: In this retrospective cohort study, prenatal and postnatal data of all newborns diagnosed with CDH between January 2004 and December 2012 in a single center were reviewed. Cases were classified into two groups: those with 'isolated' CDH and those with both CDH and CHA. Patients with CHA were further subclassified into those with a major or minor CHA based on the Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1), and the Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STS-EACTS) scoring systems. Patients with associated non-cardiac anomalies, including 'syndromic cases', were excluded from the analysis. Primary and secondary outcomes were survival up to 1 year of age and a need for extracorporeal membrane oxygenation (ECMO), respectively. RESULTS: Of the 180 infants with CDH, 41 were excluded because of the presence of non-cardiac associated anomalies, 118 had isolated CDH and 21 had CDH with CHA (16 with minor and five with major CHA). Receiver-operating characteristics curve analysis demonstrated that the best cut-off for survival was when the score for CHA was ≤ 2 for both RACHS-1 (area under the curve (AUC), 0.74 (P = 0.04); sensitivity, 80.0%; specificity, 87.5%) and STS-EACTS (AUC, 0.83 (P = 0.03); sensitivity, 100%; specificity, 87.5%). Survival rate at 1 year was significantly lower in those with CHD and a major CHA (40.0%; P = 0.04) than in those with isolated CDH (77.1%) and those with CDH and a minor CHA (81.3%). We found no significant differences among the groups with regard to the need for ECMO. CONCLUSIONS: In general, a milder form of CHA does not appear to have a negative impact on the survival of infants with CDH. However, mortality appears to be significantly higher in infants with CDH and a major form of CHA. The scoring systems appear to be useful as predictors for classifying the effects of CHA in this population of patients.

Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing first-trimester screening.

OBJECTIVES: Targeted non-invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT. METHODS: This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype. RESULTS: cFTS was completed in 193638 pregnancies. 10205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (NT) thickness (≥ 3.5 mm), with abnormal levels of free ß-human chorionic gonadotropin (<0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A<0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%. CONCLUSIONS: A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT.

Significance of septa in first trimester increased nuchal translucency thickness.

PURPOSE: The objective of this study was to investigate perinatal outcome in cases of increased nuchal translucency (NT) with or without cystic hygroma (CH), and to determine whether first-trimester CH engenders a greater risk than simple increased NT. METHODS: In this retrospective study, data from singleton pregnancies in which fetal NT was found to be 3 mm or more at the 11 + 0 to 13 + 6 weeks scan were reviewed. Cases were classified into two groups, namely 'CH' and 'increased NT'. RESULTS: Of the 76 cases with increased NT, 30 (39.4 %) presented with CH. NT measurement was significantly higher in the CH group (7.25 vs. 3.5 mm, p < 0.001). Abnormal fetal karyotype, major chromosomal anomalies in chromosomally normal fetuses, and adverse outcome were significantly more frequent in the CH group as compared with the increased NT group (p = 0.019, p = 0.021, and p = 0.001, respectively). Regression analysis revealed that NT thickness was the only significant variable in the prediction of chromosomal defect and/or major congenital anomaly (OR 2.05, 95 % CI 1.23-3.42, p = 0.005). CONCLUSION: Cystic hygroma results in poorer outcome due to higher NT measurement, and the thickness of NT rather than the presence of septa should be the mainstay of prenatal counseling in cases of increased NT in the first trimester.

Identifying a failure-to-thrive fraternal twin profile with 3q29 deletion syndrome.

In 2005, the 3q29 deletion syndrome was identified and defined as a rare chromosomal anomaly that effects approximately one in 30,000-40,000 children. It has a complex neuropsychiatric profile, often resulting in developmental delays, intellectual disabilities, attentional deficits, classic physical traits, and behavioral health disturbances, including social and emotional issues. Rarely has this syndrome been seen and evaluated in fraternal twins, only one of whom has the 3q29 deletion syndrome. This case study highlights Twin 1's strengths and weaknesses and compares her 2020 neuropsychological data, including a comparison of her Reitan-Indiana Neuropsychological Battery (RINB) results to her 2022 profile, which reveals a failure-to-thrive profile.

Syndromic non-compaction of the left ventricle: associated chromosomal anomalies.

Non-compaction of the left ventricle (NCLV) is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intertrabecular recesses. Associated extracardiac anomalies occur in 14-66% of patients of different series, while chromosomal anomalies were reported in sporadic cases. We investigated the prevalence of chromosomal imbalances in 25 syndromic patients with NCLV, using standard cytogenetic, subtelomeric fluorescent in situ hybridization, and array-comparative genomic hybridization (CGH) analyses. Standard chromosome analysis disclosed an abnormality in three (12%) patients, including a 45,X/46,XX mosaic, a 45,X/46,X,i(Y)(p11) mosaic, and a de novo Robertsonian 13;14 translocation in a child affected by hypomelanosis of Ito. Cryptic chromosome anomalies were found in six (24%) cases, including 1p36 deletion in two patients, 7p14.3p14.1 deletion, 18p subtelomeric deletion, 22q11.2 deletion associated with velo-cardio-facial syndrome, and distal 22q11.2 deletion, each in one case. These results recommend accurate clinical evaluation of patients with NCLV, and suggest that chromosome anomalies occur in about one third of syndromic NCLV individuals, without metabolic/neuromuscular disorder. Array-CGH analysis should be included in the diagnostic protocol of these patients, because different submicroscopic imbalances are causally associated with this disorder and can pinpoint candidate genes for this cardiomyopathy.

First Trimester Screening Tests Pregnancy and Trisomy 13 Syndrome, Sex Chromosome Aneuploidy in Iran: A Cross-Sectional Study.

BACKGROUND: Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy. MATERIALS AND METHODS: In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown-rump length (CRL) and pregnancy-associated plasma protein-A (PAPP-A), and free beta of human chorionic gonadotropin (fßhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated. RESULTS: The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high-risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P<0.05). The average serum fßhCG and PAAP-A levels in high-risk group for T13 were 0.42 and 0.31, respectively. Significant correlation was observed between decrease fßhCG, PAPP-A and T13 levels and increase fßhCG levels and SCA levels (P<0.05). No Significant correlation was observed between PAPP-A levels and SCA levels (P>0.05). CONCLUSION: Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities.

Elizabethkingia meningosepticum infections with varied presentations and different antimicrobial susceptibility - A case series.

We report three sporadic infections by Elizabethkingia meningosepticum from Government Medical College Kozhikode in Kerala state, South India over a period of three years. Two cases were commenced in the community in immunocompromised children beyond the newborn period, but both recovered promptly. Another was a hospital-acquired meningitis in a newborn baby who developed neurologic sequelae. In contrast to widespread antimicrobial resistance exhibited by this pathogen, there was good susceptibility to commonly used antimicrobials such as ampicillin, cefotaxime, piperacillin, ciprofloxacin, and vancomycin. Whilst ß lactam antibiotics are found effective in the treatment of Elizabethkingia septicaemia of children, piperacillin-tazobactam, vancomycin combination seems effective empiric choice of antibiotics for neonatal meningitis due to Elizabethkingia; there is a need for guidelines for the management of this infection, especially in neonatal meningitis.

[Clinical Characteristics of Multiple Myeloma Patients with Early Relapse].

OBJECTIVE: To analyze the clinical characteristics of multiple myeloma(MM) patients with early relapse. METHODS: A total of 50 MM patients with early relapse (≤12 months) and 50 matched controls with late relapse (>12 months) were selected. The time from diagnosis to relapse and related clinical data of the 100 patients were retrospectively analyzed, and the factors associated with early relapse were identified. Kaplan-Meier curve was used to analyze the overall survival (OS) time of the whole cohort. Area under the curve (AUC) was used to evaluate the effect of circulating plasma cells on early recurrence of the patients. RESULTS: The results showed that high-risk cytogenetics (FISH) (P=0.005), and ISS stage III (P=0.008) were associated with early recurrence of the patients. For patients with early relapse, high-risk FISH showed poor survival. Compared with the patients with late relapse, most of the chromosome karyotype of patients with early relapse showed quantitative and structural abnormalities. The expression of circulating plasma cells was significantly increased in patients with early recurrence group (P=0.0318). The response to initial treatment was poor in the early recurrence group (P=0.001), and the prognosis was significantly worse than those in the late recurrence group (median OS: 38 vs 81 months, P=0.002). CONCLUSION: Early relapse is a marker poor prognostic in MM patients, and such patients should be focused on the improving their prognosis.

Understanding the neuropsychological effects of 3q29 deletion Syndrome: A fraternal twin case study.

In 2005, the 3q29 Deletion Syndrome was identified and defined as a rare chromosomal anomaly that effects approximately one in 30,000-40,000 children. It has a complex neuropsychiatric profile but often results in developmental delay, intellectual disability, attentional deficits, classic physical traits, behavioral health disturbances, as well as social and emotional issues. Rarely has this syndrome been seen and evaluated in fraternal twins, only one of whom has the 3q29 Deletion Syndrome. This case study highlights the twins' strengths and weaknesses and describes their neuropsychological profiles, including a comparison of their results of the Reitan-Indiana Neuropsychological Battery (RINB). Medication management and psychoeducational interventions are outlined.

Congenital anomalies in breech presentation: A nationwide record linkage study.

Our study aimed to determine if congenital anomalies are associated with breech presentation at delivery. We conducted a nationwide, retrospective population-based record linkage study and analyzed all singleton births in Finland from 1996 to 2016 using the mandatory health register data collected by the Finnish Institute for Health and Welfare. We compared all major congenital anomalies detected during pregnancy, birth, or the first year of life according to the fetus's presentation at the time of delivery using X2 -square statistic and Student's t test. We adjusted the results for known risk factors for congenital anomalies to estimate adjusted odds ratios and 95% confidence intervals. Fetuses in breech presentation at delivery had an increased risk for congenital anomalies (6.5%) compared with fetuses in cephalic presentation (3.6%), P < .001. Breech presentation was associated with nearly all types of examined congenital anomalies. The strongest associations were observed with congenital deformities of the hip, the central nervous system, the respiratory system, and the musculoskeletal system. Our study supports the theory that breech presentation is, in many cases, a symptom of a fundamental problem in fetal morphogenesis or function. Neonates born in the breech presentation have a higher risk of congenital anomalies and should undergo a postnatal screening.

Multiple Congenital Anomalies in a Patient with Interstitial 6q26 Deletion.

We report a preterm male neonate presenting with a lumbosacral meningomyelocele, type II Arnold Chiari malformation, hypoplasia of the aortic arch, bicuspid aortic valve, ventricular septal defect, secundum atrial septal defect, multicystic dysplastic kidney, and hydronephrosis. Analysis with whole genome SNP microarray revealed an interstitial deletion of about 237 kb in chromosome 6q26. Long contiguous stretches of homozygosity (>3 Mb) were seen in 18 chromosomes with a total genomic size of 219 Mb. The phenotype seen in our patient has not been reported in association with the genes in the homozygous regions. However, our patient shares many phenotypic features with other reported cases that have shown a deletion in the same region of chromosome 6.