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Annals of Cardiac Anaesthesia Jan 2024The quadricuspid aortic valve is a rare congenital anomaly, usually associated with aortic regurgitation requiring surgical intervention. It may be associated with other...
The quadricuspid aortic valve is a rare congenital anomaly, usually associated with aortic regurgitation requiring surgical intervention. It may be associated with other congenital anomalies such as coronary anomalies, patent ductus arteriosus, ventricular septal defect, pulmonary stenosis, and subaortic stenosis. The diagnosis is generally established by either transthoracic or transesophageal echocardiography. Herein, we report a case of a 52-year-old woman who was diagnosed to have quadricuspid aortic valve by intraoperative transesophageal echocardiography.
Topics: Humans; Female; Aortic Valve; Middle Aged; Echocardiography, Transesophageal; Aortic Valve Insufficiency; Heart Defects, Congenital
PubMed: 38722121
DOI: 10.4103/aca.aca_110_23 -
The Journal of Hand Surgery, European... Sep 2023This review article provides a comprehensive overview of thalidomide upper limb embryopathy including updates about its pathogenesis, a historical account of the... (Review)
Review
This review article provides a comprehensive overview of thalidomide upper limb embryopathy including updates about its pathogenesis, a historical account of the management of the paediatric thalidomide patient, experience with management of the adult patient, as well as creating awareness about early onset age-related changes associated with limb differences. Despite its withdrawal from the market in November 1961, novel discoveries have meant thalidomide is licensed again and currently still in use to treat a variety of conditions, including inflammatory disorders and some cancers. Yet, if not used safely, thalidomide still has the potential to cause damage to the embryo. Recent work identifying thalidomide analogues that retain clinical benefits yet without the harmful effects are showing great promise. Understanding the problems thalidomide survivors face as they age can allow surgeons to support their unique healthcare issues and translate these principles of care to other congenital upper limb differences.
Topics: Adult; Humans; Child; Female; Thalidomide; Abnormalities, Multiple; Upper Extremity; Fetal Diseases
PubMed: 37226469
DOI: 10.1177/17531934231177425 -
The British Journal of Ophthalmology Nov 2023Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant...
BACKGROUND/AIMS
Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant proportion of childhood blindness worldwide. Clear understanding of MAC aetiology and comorbidities is essential to providing patients with appropriate care. However, current management is unstandardised and molecular diagnostic rates remain low, particularly in those with unilateral presentation. To further understanding of clinical and genetic management of patients with MAC, we charted their real-world experience to ascertain optimal management pathways and yield from molecular analysis.
METHODS
A prospective cohort study of consecutive patients with MAC referred to the ocular genetics service at Moorfields Eye Hospital between 2017-2020.
RESULTS
Clinical analysis of 50 MAC patients (15 microphthalmia; 2 anophthalmia; 11 coloboma; and 22 mixed) from 44 unrelated families found 44% had additional ocular features (complex) and 34% had systemic involvement, most frequently intellectual/developmental delay (8/17). Molecular analysis of 39 families using targeted gene panels, whole genome sequencing and microarray comparative genomic hybridisation identified genetic causes in, 28% including novel variants in six known MAC genes (, , , , and ), and a molecular diagnostic rate of 33% for both bilateral and unilateral cohorts. New phenotypic associations were found for (bilateral sensorineural hearing loss) and (unilateral microphthalmia).
CONCLUSION
This study highlights the importance of thorough clinical and molecular phenotyping of MAC patients to provide appropriate multidisciplinary care. Routine genetic testing for both unilateral and bilateral cases in the clinic may increase diagnostic rates in the future, helping elucidate genotype-phenotype correlations and informing genetic counselling.
Topics: Humans; Anophthalmos; Microphthalmos; Coloboma; Prospective Studies; Eye Abnormalities; Eye Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 36192130
DOI: 10.1136/bjo-2022-321991 -
European Radiology Nov 2023To investigate the role of MRI in the diagnosis and classification of fetal microtia.
OBJECTIVE
To investigate the role of MRI in the diagnosis and classification of fetal microtia.
METHODS
Ninety-five fetuses with suspected microtia based on ultrasound and MRI performed within 1 week were enrolled in this study. The diagnosis based on MRI was compared with postnatal diagnosis. Among the microtia cases suspected on the basis of MRI, mild and severe cases were further classified. In addition, external auditory canal (EAC) atresia was evaluated by MRI in 29 fetuses with a gestational age > 28 weeks, and the accuracy of MRI in the diagnosis and classification of microtia was determined.
RESULTS
Of 95 fetuses, 83 were considered to have microtia on the basis of MRI, 81 were confirmed to have microtia, and 14 were found to be normal according to postnatal diagnosis. Among 190 external ears in 95 fetuses, 40 ears were suspected to have mild microtia, and 52 ears were suspected to have severe microtia on the basis of MRI. According to the postnatal diagnosis, mild and severe microtia were confirmed in 43 and 49 ears, respectively. Among the 29 fetuses with a gestational age > 28 weeks, 23 ears were suspected to have EAC atresia according to MRI and 21 ears were ultimately confirmed to have EAC atresia. The accuracy of MRI in diagnosing microtia and EAC atresia was 93.68% and 93.10%, respectively.
CONCLUSION
MRI shows good performance in diagnosing fetal microtia and has the potential to evaluate its severity on the basis of classification and EAC status.
CLINICAL RELEVANCE STATEMENT
This study was aimed at investigating the role of MRI in the diagnosis and classification of fetal microtia. MRI shows good performance and can help evaluate microtia severity and EAC atresia, thus allowing for better clinical management.
KEY POINTS
• MRI is a useful adjunct to prenatal ultrasound. • MRI has a higher accuracy rate than ultrasound in diagnosing fetal microtia. • The accurate classification of fetal microtia and the diagnosis of external auditory canal atresia through MRI may help guide clinical management.
Topics: Pregnancy; Female; Humans; Infant; Congenital Microtia; Ear, External; Prenatal Diagnosis; Fetus; Magnetic Resonance Imaging; Ultrasonography, Prenatal; Retrospective Studies
PubMed: 37311804
DOI: 10.1007/s00330-023-09816-5 -
The Journal of Maternal-fetal &... Dec 2024The etiology of congenital talipes equinovarus (CTEV) is unknown, and the relationship between chromosome microdeletion/microduplication and fetal CTEV is rarely...
OBJECTIVE
The etiology of congenital talipes equinovarus (CTEV) is unknown, and the relationship between chromosome microdeletion/microduplication and fetal CTEV is rarely reported. In this study, we retrospectively analyzed fetal CTEV to explore the relationship among the CTEV phenotype, chromosome microdeletion/microduplication, and obstetric outcomes.
METHODS
Chromosome karyotype analysis and single nucleotide polymorphism (SNP) array were performed for the 68 fetuses with CTEV.
RESULTS
An SNP array was performed for 68 fetuses with CTEV; pathogenic copy number variations (CNVs) were detected in eight cases (11.8%, 8/68). In addition to one case consistent with karyotype analysis, the SNP array revealed seven additional pathogenic CNVs, including three with 22q11.21 microdeletions, two with 17p12p11.2 microduplications, one with 15q11.2 microdeletions, and one with 7q11.23 microduplications. Of the seven cases carrying pathogenic CNVs, three were tested for family genetics; of these, one was , and two were inherited from either the father or mother. In total, 68 fetuses with CTEV were initially identified, of which 66 cases successfully followed-up. Of these, 9 were terminated, 2 died in utero, and 55 were live births. In 9 cases, no clinical manifestations of CTEV were found at birth; the false-positive rate of prenatal ultrasound CTEVdiagnosis was thus 13.6% (9/66).
CONCLUSION
CTEV was associated with chromosome microdeletion/microduplication, the most common of which was 22q11.21 microdeletion, followed by 17p12p11.2 microduplication. Thus, further genomic detection is recommended for fetuses with CTEV showing no abnormalities on conventional karyotype analysis.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Clubfoot; Retrospective Studies; DNA Copy Number Variations; Follow-Up Studies; Fetus; Genomics; Prenatal Diagnosis
PubMed: 38151241
DOI: 10.1080/14767058.2023.2299113 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Aug 2023This study aimed to explore the relationship between alveolar cleft and secondary nasal deformity post unilateral cleft lip repair in adults.
OBJECTIVES
This study aimed to explore the relationship between alveolar cleft and secondary nasal deformity post unilateral cleft lip repair in adults.
METHODS
A total of 27 patients aged 16-30 years old with unilateral secondary nasal deformity and alveolar cleft were included, 13 of whom underwent bone grafting. Spiral CT data of all preoperative and postoperative patients who had alveolar bone grafting were collected. Then, Mimics software was used for three-dimensional reconstruction to evaluate the correlation between the width, height, and volume of the alveolar cleft and those of the nasal deformity. The difference in nasal deformity before and after alveolar bone grafting was also explored.
RESULTS
The width of the alveolar cleft was positively correlated with the difference in bilateral nostril floor width (<0.05). As the effective depth of the alveolar cleft increased, the sub-alare inclination angle largened (<0.05). However, no significant difference was found in the nasal deformity between before and after alveolar bone grafting.
CONCLUSIONS
Alveolar cleft is closely related to secondary nasal deformities post unilateral cleft lip repair, especially nasal floor deformities. Alveolar bone grafting benefits adult patients for the improvement of secondary nasal deformities post unilateral cleft lip repair.
Topics: Humans; Adult; Adolescent; Young Adult; Nose; Cleft Lip; Rhinoplasty; Imaging, Three-Dimensional; Treatment Outcome; Cleft Palate
PubMed: 37474474
DOI: 10.7518/hxkq.2023.2022466 -
International Journal of Molecular... Feb 2024The use of next-generation sequencing has provided new insights into the causes and mechanisms of congenital heart disease (CHD). Examinations of the whole exome... (Review)
Review
The use of next-generation sequencing has provided new insights into the causes and mechanisms of congenital heart disease (CHD). Examinations of the whole exome sequence have detected detrimental gene variations modifying single or contiguous nucleotides, which are characterised as pathogenic based on statistical assessments of families and correlations with congenital heart disease, elevated expression during heart development, and reductions in harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities are enriched for gene classes meeting these criteria, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data have revealed the expression of genes associated with CHD in specific cell types, and emerging evidence suggests that genetic mutations disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole-genome sequencing studies.
Topics: Humans; Heart Defects, Congenital; Mutation; Exome; Whole Genome Sequencing; Genomics; DNA Copy Number Variations
PubMed: 38339013
DOI: 10.3390/ijms25031734 -
Medicina (Kaunas, Lithuania) Sep 2023: The traditional approach in managing wide cleft lip deformities involves presurgical nasoalveolar molding (NAM) therapy followed by surgical cleft lip repair between...
: The traditional approach in managing wide cleft lip deformities involves presurgical nasoalveolar molding (NAM) therapy followed by surgical cleft lip repair between three and six months of age. This institution has implemented an early cleft lip repair (ECLR) protocol where infants undergo primary cleft lip repair between two and five weeks of age without NAM. This study aims to present this institution's ECLR repair protocol over the past eight years from 188 consecutive patients with unilateral or bilateral CL/P deformity. : Retrospective review was conducted at Children's Hospital Los Angeles evaluating patients who underwent ECLR before three months of age and were classified as American Society of Anesthesiologists (ASA) class I or II from 2015-2022. Anthropometric analysis was performed, and pre- and postoperative photographs were evaluated to assess nasal and lip symmetry. : The average age at cleft lip repair after correcting for gestational age was 1.0 ± 0.5 months. Mean operative and anesthetic times were 120.3 ± 33.0 min and 189.4 ± 35.4, respectively. Only 2.1% (4/188) of patients had postoperative complications. Lip revision rates were 11.4% (20/175) and 15.4% (2/13) for unilateral and bilateral repairs, respectively, most of which were minor in severity (16/22, 72.7%). Postoperative anthropometric measurements demonstrated significant improvements in nasal and lip symmetry ( < 0.001). : This analysis demonstrates the safety and efficacy of ECLR in correcting all unilateral cleft lip and nasal deformities of patients who were ASA classes I or II. At this institution, ECLR has minimized the need for NAM, which is now reserved for patients with bilateral cleft lip, late presentation, or comorbidities that preclude them from early repair. ECLR serves as a valuable option for patients with a wide range of cleft severity while reducing the burden of care.
Topics: Infant; Child; Humans; Infant, Newborn; Cleft Lip; Cleft Palate; Nose; Retrospective Studies; Preoperative Care; Treatment Outcome
PubMed: 37893459
DOI: 10.3390/medicina59101741 -
European Journal of Preventive... Jun 2024Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association...
AIMS
Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL-lowering, overall and through PCSK9 drug targets, on congenital malformations.
METHODS AND RESULTS
Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1 320 016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted, respectively, from a GWAS on 10 186 individuals and from the genotype-tissue expression project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n = 342 499) for eight categories of congenital malformations affecting multiple systems. Genetically proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems [OR 2.70, 95% confidence interval (CI) 1.30-5.63, P = 0.018], the skin (OR 2.23, 95% CI 1.33-3.75, P = 0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal, and limb association (VACTERL) (OR 1.51, 95% CI 1.16-1.96, P = 0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive of horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations.
CONCLUSION
These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.
Topics: Humans; Cholesterol, LDL; Female; Genome-Wide Association Study; Proprotein Convertase 9; PCSK9 Inhibitors; Mendelian Randomization Analysis; Pregnancy; Risk Factors; Abnormalities, Drug-Induced; Biomarkers; Risk Assessment; Serine Proteinase Inhibitors; Genetic Predisposition to Disease; Phenotype; Polymorphism, Single Nucleotide; Anticholesteremic Agents
PubMed: 38294056
DOI: 10.1093/eurjpc/zwad402 -
BMC Pregnancy and Childbirth Mar 2024To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020.
OBJECTIVE
To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020.
METHODS
Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016-2020. Prevalence of birth defects (polydactyly or syndactyly) is the number of cases per 1000 births (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ) were used to determine trends in prevalence by year. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with polydactyly and syndactyly.
RESULTS
Our study included 847,755 births, and 14,459 birth defects were identified, including 1,888 polydactyly and 626 syndactyly cases, accounting for 13.06% and 4.33% of birth defects, respectively. The prevalences of total birth defects, polydactyly, and syndactyly were 17.06‰ (95%CI: 16.78-17.33), 2.23‰ (95%CI: 2.13-2.33), and 0.74‰ (95%CI: 0.68-0.80), respectively. Most polydactyly (96.77%) and syndactyly (95.69%) were diagnosed postnatally (within 7 days). From 2016 to 2020, the prevalences of polydactyly were 1.94‰, 2.07‰, 2.20‰, 2.54‰, and 2.48‰, respectively, showing an upward trend (χ = 19.48, P < 0.01); The prevalences of syndactyly were 0.62‰, 0.66‰, 0.77‰, 0.81‰, and 0.89‰, respectively, showing an upward trend (χ = 10.81, P = 0.03). Hand polydactyly (2.26‰ vs. 1.33‰, OR = 1.69, 95%CI: 1.52-1.87) and hand syndactyly (0.43‰ vs. 0.28‰, OR = 1.42, 95%CI: 1.14-1.76) were more common in males than females. Polydactyly (2.67‰ vs. 1.93‰, OR = 1.38, 95%CI: 1.26-1.51) and syndactyly (0.91‰ vs. 0.62‰, OR = 1.47, 95%CI: 1.26-1.72) were more common in urban areas than in rural areas. Compared to maternal age 25-29, hand polydactyly was more common in maternal age < 20 (2.48‰ vs. 1.74‰, OR = 1.43, 95%CI: 1.01-2.02) or ≥ 35 (2.25‰ vs. 1.74‰, OR = 1.30, 95%CI: 1.12-1.50).
CONCLUSION
In summary, we have described the prevalence and epidemiology of polydactyly and syndactyly from hospital-based surveillance in Hunan Province, China, 2016-2020. Our findings make some original contributions to the field, which may be valuable for future research.
Topics: Male; Female; Humans; Adult; Polydactyly; Syndactyly; Maternal Age; China; Prevalence; Congenital Abnormalities
PubMed: 38521899
DOI: 10.1186/s12884-024-06417-y