Congenital Anomalies最新文献

ZNF335 plays an essential role in the neurogenesis of the human brain, and pathogenic variants of ZNF335 are associated with primary or secondary (postnatal) microcephaly. We performed exome sequencing in a patient with secondary microcephaly, epilepsy, global developmental delay, and dysmorphic craniofacial features, and identified compound heterozygous missense and intronic variants in ZNF335 (NM_022095.4:c.1504T>G, p.(Tyr502Asp) and c.1665 + 6T>A). Using a minigene assay, we demonstrated that the intronic variant causes aberrant splicing, resulting in significantly reduced ZNF335 protein levels. In addition, a review of the clinical findings of previously reported 10 patients with ZNF335 variants revealed that microcephaly was present in all patients, about half of them were secondary, and epilepsy and severe developmental delay were also quite recurrent findings.

Non-syndromic cleft lip and/or palate (NCL/P) is a congenital craniofacial anomaly with significant psychosocial and economic impacts. In Ethiopia, the prevalence of NCL/P and access to specialized care are not well documented. This study aimed to evaluate the knowledge and awareness of NCL/P among families of affected children and dental school students in Ethiopia and explore their perceptions and attitudes toward NCL/P. From 2009 to 2018, we conducted questionnaire surveys involving 86 patients with NCL/P and their families in the towns of Addis Ababa and Butajira, including 161 students from the School of Dentistry, Addis Ababa University. The surveys assessed the knowledge, perceptions, and attitudes toward NCL/P and their social implications. The majority of patients with NCL/P were born at home and in low-income families. Concerns about the future social life of patients were prominent, with stigma and discrimination reported by 32% of the patients' families. Among the dental school students, 66% had some knowledge of NCL/P, primarily from media sources. Students perceived higher levels of societal blame towards mothers of patients with NCL/P than reported by the patients' families. This study revealed significant gaps in the knowledge and awareness regarding NCL/P among dental school students. It also revealed the substantial social stigma that the patients affected by NCL/P and their families faced in Ethiopia. Enhancing public education and providing comprehensive multidisciplinary care is crucial for improving the quality of life of patients with NCL/P in Ethiopia.

The Fukushima Daiichi Nuclear Disaster (FDND) occurred in 2011, which occurred after the Great East Japan Earthquake. However, how the incidence of radiation-induced malformations in Fukushima has been affected by FDND remains to be elucidated. To address this, we analyzed birth data from Fukushima and other areas in Japan from the International Clearinghouse for Birth Defects Surveillance and Research Japan Center, including information on birth defects between January 2010 and December 2022. Among the registered birth defects, microcephaly, microphthalmia, and neural tube defects were classified as radiation-induced malformations. Our study included 90 433 births in Fukushima, accounting for 52.6% of all births. Among these, birth defects were observed in 1376 (1.52%) births, of which 28 (0.031%) were diagnosed with radiation-induced malformations. With regard to other areas in Japan, 1 323 391 births, which accounted for 10.9% of all births, were registered; births with birth defects and radiation-induced malformations were observed in 37 490 (3.67%) and 889 (0.067%), respectively. Because sampling bias was suspected, we compared the rates of radiation-induced malformations in Fukushima and other areas in Japan by adjusting the incidence in Fukushima with the incidences of ventricular septal defects in both areas. However, there was no statistically significant difference between them. Our results, which covered the largest number of births in Fukushima, did not find a significant increase in the incidence of radiation-induced malformations in Fukushima since FDND.

This study aimed to assess the prevalence of soft markers on second-trimester sonography in low-risk and screening naïve Indian antenatal women and determine their association with aneuploidy. Soft markers were evaluated through ultrasound, and likelihood ratios (LRs) and modified risk (MR) for aneuploidy were calculated. Pregnant women with a MR >1:250 underwent genetic counseling and invasive testing, whereas those with a lower risk received follow-up. Associations were estimated via Fisher's exact test. A total of 4051 anomaly scans were reviewed, among which 207 (5.1%) women were found to have soft markers (SMs). These included 153 (3.7%) isolated SMs, 43 (1.06%) multiple SMs, and 11 (0.2%) SMs with structural abnormalities. The most common SM was renal pyelectasis. Invasive test uptake increased by 25% among pregnancies with isolated markers and by 55% for those with multiple SMs. A significant association was found between isolated short femur and aneuploidy (p = 0.026), and between multiple SMs and aneuploidy (p = 0.039). Soft markers in low-risk couples can lead to unnecessary invasive testing and anxiety. Genetic counseling is important for discussing relevant factors. Invasive testing for aneuploidies should be based on the modified risk, the presence of multiple SMs, or structural anomalies on ultrasonography.

Children with Down syndrome often experience obstructive sleep apnea (OSA), which can be severe and, if untreated, leads to serious complications. Polysomnography, the gold standard for diagnosing OSA, has long waiting lists and poses challenges for these children. The modified OSA-18 questionnaire may help determine the severity of OSA in this population, facilitating the study of its prevalence and risk factors. A cohort of 180 children with Down syndrome, aged 2–12 years, was enrolled from August 2020 to January 2022. Participants completed the modified OSA-18 questionnaire, where a score of 21+ indicated a high risk of severe OSA. Demographic data, prevalence, and associated risk variables were analyzed. A total of 180 participants were included. Their mean age was 8.9 ± 2.8 years, and a slight majority were male (52.2%). Most had normal weight (44.4%); 33.9% were overweight, and 21.7% had obesity. The prevalence of those at high risk for severe OSA was 19.4%. The only significant risk factor for severe OSA was obesity (p < 0.001; OR = 6.96; 95% CI = 2.65–18.28). The study found a lower prevalence of high-risk severe OSA in children than reported by polysomnography-based studies, with obesity as the sole risk factor. The research confirmed that the modified OSA-18 questionnaire is a more convenient and quicker assessment tool. Prompt assessment of obese children with Down syndrome for severe OSA is crucial to prevent sequelae.

Submucous cleft palate (SMCP) is a type of cleft lip and/or palate that is often diagnosed based on speech symptoms caused by velopharyngeal insufficiency and is frequently accompanied by complications. Although both surgery and speech therapy are treatment options, reports vary according to appropriate timing and suitability. At our hospital, patients who opted against surgery underwent speech therapy with positive results. This study aimed to evaluate the progression of velopharyngeal function (VPF) over time in non-operated patients with SMCP to formulate a new treatment approach. Fifty-three patients with SMCP who underwent VPF evaluation and over 1 year of speech therapy at the Cleft Lip and Palate Center of Aichi Gakuin University Dental Hospital between 2002 and 2022 were included. The patients were classified into with-complications and without-complications groups, and data on VPF evaluation, therapy duration, and progress were collected. Twenty patients experienced complications, while 33 did not. In the without-complications group, a significant improvement in VPF was observed after speech therapy. At the lowest VPF, five patients required surgery, but by the final evaluation, all patients experienced improvements, with no case of “poor.” Conservative treatment through long-term speech therapy demonstrated significant improvement in velopharyngeal function for non-complicated SMCP cases, suggesting it as a viable alternative to surgery in selected patients. This study highlights the clinical relevance of conservative speech therapy as a cost-effective, accessible alternative to surgery, particularly in resource-limited settings, offering comparable outcomes in non-complicated SMCP cases and potentially reducing healthcare burdens.

Congenital anomalies pose significant challenges in medicine due to their high morbidity and mortality rates. These anomalies are more prevalent in low- and middle-income countries, where variations exist in intensive care admissions and treatment protocols for critical cases. Our study aimed to investigate the prevalence of congenital anomalies among patients under the age of one admitted to the level III intensive care unit. The study focused on diagnosing anomalies, reasons for intensive care admission, structural analysis, classification based on system involvement, surgical requirements, duration of intensive care stay, and treatment outcomes. A total of 8276 patients were admitted to the intensive care unit of our Pediatric Research Institute between 2019 and 2022. Among them, 1256 patients (15.2%) were diagnosed with congenital anomalies. The majority of infants (73.3%) were admitted within the neonatal period, whereas 21.2% were admitted from 29 days to 6 months and 5.5% between 6 months and 1 year of age. Ultimately, 1084 (86.3%) patients survived, and 172 (13.7%) patients died. Structural analysis of congenital anomalies in a tertiary intensive care unit in Azerbaijan indicated comparable frequencies of anomalies, surgical requirements, and mortality rates to those published in articles from developed countries. Additionally, differences in anomaly distribution among organ systems were observed, with congenital heart defects being more prevalent.

Polydactyly is a congenital anomaly characterized by additional fingers and/or toes, with varying prevalence rates and characteristics across different populations. The current study investigated polydactyly's prevalence and characteristics between January 2015 and December 2022 retrospectively at two tertiary hospitals, one in Riyadh and one in Jeddah, Saudi Arabia. Data on the type and location of polydactyly, together with associated anomalies, were examined. The study identified 176 cases of polydactyly, with the majority (77%) in Riyadh. The average diagnosis was at age 8.9 months; there was a notable male predominance (57%). Over the 8 years examined, the polydactyly prevalence rate among 95 452 Saudi neonates was 97 per 10 000 live births. The occurrence was greater in the upper (49%) than in the lower limbs (33%). Unilateral cases were seen in 47% of hands and 23% of feet, and bilateral cases in 26% of hands and 22% of feet. In addition, the most prevalent form of polydactyly in both hands and feet was postaxial, observed in 34% and 30%, respectively. In contrast, the preaxial type was observed in 15% of hands and 3% of feet. Family history, additional anomalies, and other health conditions were noted in 10%, 45%, and 34% of cases, respectively. The higher occurrence of polydactyly in the hands and its predominant unilateral manifestation, together with its association with familial patterns and specific syndromes, emphasizes the potential interplay between genetic and environmental factors.

Heterozygous loss-of-function variants in heterogeneous nuclear ribonucleoprotein U (HNRNPU) cause early-onset developmental and epileptic encephalopathy with multiple congenital anomalies. Limited clinical information is currently available on HNRNPU-related neurodevelopmental disorder. The patient was a 1-year-old Japanese girl with developmental delay, hypotonia, early-onset epilepsy, respiratory distress, and distinctive facial features, including ptosis, epicanthus, a prominent nasal bridge, a wide nasal floor, a cleft soft palate, and micrognathia. Respiratory distress was caused by pharyngeal stenosis and laryngomalacia, which gradually worsened, necessitating a scheduled tracheostomy at 1 year and 7 months of age. We performed whole-exome sequencing and identified a novel de novo nonsense variant in HNRNPU. We herein describe the first case of HNRNPU-related neurodevelopmental disorder with severe airway anomalies and a novel nonsense variant, thereby expanding the phenotypic spectrum

Pregnancy loss is a significant concern worldwide, encompassing miscarriage and stillbirth. Miscarriage, defined as the loss of a baby before 28 weeks of gestation, accounts for approximately 15% of pregnancies. Stillbirth, occurring at or after 28 weeks of gestation, affects nearly 2.0 million pregnancies annually, predominantly in low- and middle-income regions. This study aims to investigate the potential of Anemarrhena rhizome (AR) herbal medicine in mitigating pregnancy loss and reducing the incidence of cleft palate in A/J mice models. A total of 390 6-week-old A/J mice were used for the study. Three different dosages of dried AR (6, 12, and 18 g) were boiled to prepare water extracts. The mice were divided into experimental groups receiving these extracts and a control group. Pregnancy outcomes, including fetal mortality rates and incidence of cleft palate, were assessed. The experimental groups receiving AR herbal medicine demonstrated significantly lower fetal mortality rates compared to the control group. Additionally, the incidence of cleft palate was notably reduced in the experimental groups, with the AR 6 g and AR 12 g groups showing significant reductions compared to the control group. AR herbal medicine shows promise in mitigating pregnancy loss and reducing the incidence of cleft palate in A/J mice models. These findings suggest the potential of AR as a therapeutic agent for improving fetal health outcomes. Further research is warranted to elucidate the underlying mechanisms and optimize dosage strategies for maximizing its therapeutic benefits in pregnancy-related complications.