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Circulation Research Jun 2024Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in... (Review)
Review
Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.
Topics: Humans; Lymphatic Diseases; Vascular Diseases; Animals; Vascular Malformations; Lymphatic Vessels; Genetic Predisposition to Disease
PubMed: 38900856
DOI: 10.1161/CIRCRESAHA.124.323181 -
Seminars in Pediatric Surgery Jun 2024Congenital heart disease affects 1/100 live births and is one of the most common congenital abnormalities. The relationship between congenital heart disease and... (Review)
Review
Congenital heart disease affects 1/100 live births and is one of the most common congenital abnormalities. The relationship between congenital heart disease and lymphatic abnormalities and/or dysfunction is well documented and can be grossly divided into syndromic and non-syndromic etiologies. In patients with genetic syndromes (as examples listed above), there are known primary abnormal lymphatic development leading to a large pleiotropic manifestation of lymphatic dysfunction. Non-syndromic patients, or those without clear genetic etiologies for their lymphatic dysfunction, are often thought to be secondary to physiologic abnormalities as sequelae of congenital heart disease and palliative surgeries. Patients with congenital heart disease and lymphatic dysfunction have a wide variety of clinical manifestations for which there were not many therapeutic interventions available. The development of new imaging techniques allows us to understand better the pathophysiology of these problems and to develop different percutaneous interventions aiming to restore normal lymphatic function.
Topics: Humans; Heart Defects, Congenital; Lymphatic Abnormalities; Lymphatic Diseases
PubMed: 38830312
DOI: 10.1016/j.sempedsurg.2024.151419 -
American Journal of Medical Genetics.... Aug 2023PHACES syndrome is a multiple congenital disorder with unknown etiology that is characterized by Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac...
PHACES syndrome is a multiple congenital disorder with unknown etiology that is characterized by Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/coarctation of the aorta, Eye anomalies, and Sternal cleft. Compound heterozygous or homozygous TMEM260 variants cause structural heart defects and renal anomalies syndrome (SHDRA). We describe a 10-year-old male patient with a PHACES-like syndrome and TMEM260 compound heterozygous variants who demonstrated overlapping phenotypes between the two syndromes. He presented with truncus arteriosus, supraumbilical raphe, ophthalmological abnormality, vertebral abnormality, borderline intellectual disability, and hearing loss. He had normal serum creatinine. In proband exome sequencing, compound heterozygous TMEM260 variants (NM_017799.4 c.1617delG p.(Trp539Cysfs*9)/c.1858C > T p.(Gln620*)) were identified. Twelve patients have been reported with TMEM260-related SHDRA: 10 had truncus arteriosus and 6 had renal failure. One previously reported patient had facial port wine nevus and another patient had supraumbilical raphe, which are the cardinal signs for PHACES syndrome. TMEM260-related SHDRA could share overlapping clinical features with PHACES syndrome. This report expands the phenotypic spectrum of a TMEM260-related disorder.
Topics: Male; Humans; Syndrome; Heart Defects, Congenital; Aortic Coarctation; Eye Abnormalities; Neurocutaneous Syndromes
PubMed: 37183566
DOI: 10.1002/ajmg.a.63245 -
Fetal and Pediatric Pathology Aug 2023VACTERL association consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis depends on the presence of at least three of...
VACTERL association consists of Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, and Limb defects. The diagnosis depends on the presence of at least three of these structural abnormalities. The clinical presentation and diagnostic prenatal imaging of VACTERL association are comprehensively reviewed. The most common feature is a vertebral anomaly, found in 60-80% of cases. Tracheo-esophageal fistula is seen in 50-80% of cases and renal malformations in 30% of patients. Limb defects including thumb aplasia/hypoplasia, polydactyly, and radial agenesis/hypoplasia are present in 40-50% of cases. Anorectal defects, like imperforate anus/anal atresia, are challenging to detect prenatally. The diagnosis of VACTERL association mostly relies on imaging techniques such as ultrasound, computed tomography, and magnetic resonance. Differential diagnosis should exclude similar diseases such as CHARGE and Townes-Brocks syndromes and Fanconi anemia. New insights into genetic etiology have led to recommendations of chromosomal breakage investigation for optimal diagnosis and counseling.
Topics: Humans; Esophagus; Trachea; Limb Deformities, Congenital; Spine; Heart Defects, Congenital; Anal Canal; Kidney; Upper Extremity Deformities, Congenital; Diagnostic Imaging
PubMed: 37195727
DOI: 10.1080/15513815.2023.2206905 -
Genes Oct 2023Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of...
Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of individuals with Axenfeld-Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with ARA/ARS or similar phenotypes affecting five different genes/regions. and explained three families each. was recently linked with syndromic cognitive impairment that includes hearing loss, dental defects, ventriculomegaly, Dandy-Walker malformation, skeletal anomalies (hip dysplasia), and other features showing a significant overlap with -ARS. Anterior segment anomalies are not currently associated with , yet our cases demonstrate ARA, congenital glaucoma, corneal neovascularization, and cataracts. The identification of variants, linked with Alagille syndrome, in three separate families with a clinical diagnosis of ARA/ARS highlights the overlapping features and high variability of these two phenotypes. Finally, intragenic variants in , , and an X chromosome deletion encompassing and (linked with ocular and dental anomalies, correspondingly) were identified in three additional cases with ARS. Accurate diagnosis has important implications for clinical management. We suggest that broad testing such as exome sequencing be applied as a second-tier test for individuals with ARS with normal results for sequencing and copy number analysis, with attention to the described genes/regions.
Topics: Humans; Transcription Factors; Homeodomain Proteins; Anterior Eye Segment; Eye Abnormalities; Ubiquitin Thiolesterase
PubMed: 37895297
DOI: 10.3390/genes14101948 -
Prenatal Diagnosis Aug 2023This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies...
OBJECTIVE
This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis.
METHODS
A total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases.
RESULTS
The trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth.
CONCLUSIONS
Prenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.
Topics: Female; Humans; Pregnancy; Prenatal Diagnosis; Whole Genome Sequencing; Exome Sequencing; Microarray Analysis; Congenital Abnormalities; Genetic Variation
PubMed: 37355983
DOI: 10.1002/pd.6402 -
Oral Diseases Sep 2023The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve,... (Review)
Review
The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis.
Topics: Humans; Goldenhar Syndrome; Facial Asymmetry; Mandible
PubMed: 36648381
DOI: 10.1111/odi.14508 -
Otolaryngologic Clinics of North America Oct 2023Congenital anomalies of the external auditory canal (EAC) are classically divided into congenital aural atresia (CAA) and congenital aural stenosis (CAS). CAA can... (Review)
Review
Congenital anomalies of the external auditory canal (EAC) are classically divided into congenital aural atresia (CAA) and congenital aural stenosis (CAS). CAA can present as an isolated anomaly, unilateral or bilateral, or in the setting of a craniofacial syndrome. Hearing testing (ABR with air and bone conduction thresholds for both ears) early in the perinatal period is important to document hearing thresholds. Hearing status thus informs parent counseling on options for hearing habilitation: Bone conducting technology is a must for children with bilateral CAA to support normal speech and language development. Bone conducting technology should be considered for children with unilateral CAA; benefits are unclear. In select candidates, atresia repair can provide improved hearing with a clean, dry, epithelialized ear canal. First branchial cleft cyst or sinus is rare; high index of suspicion is needed to diagnose along with high-resolution CT. Congenital aural stenosis (CAS) is a rare condition, and hearing testing should be similar to that in children with CAA. Early (age 4-5) CT imaging is recommended in the setting of a canal <2 mm or pinpoint canal to evaluate for trapped skin/ear canal cholesteatoma.
Topics: Child; Humans; Child, Preschool; Ear Canal; Constriction, Pathologic; Hearing; Bone Conduction; Congenital Abnormalities
PubMed: 37537101
DOI: 10.1016/j.otc.2023.06.007 -
Operative Orthopadie Und Traumatologie Feb 2024Early correction of congenital scoliosis including short fusion, while minimizing both mobility restrictions and growth impairment. (Review)
Review
OBJECTIVE
Early correction of congenital scoliosis including short fusion, while minimizing both mobility restrictions and growth impairment.
INDICATIONS
Congenital scoliosis with marked deformity, proven progression, significant compensatory curves, and/or impairment of trunk balance. Furthermore, in case of compression of neural structures or pain due to secondary degeneration.
CONTRAINDICATIONS
No absolute contraindication.
SURGICAL TECHNIQUE
Posterior approach to the apex of the deformity. In the growing spine the periosteum should only be touched at the levels where fusion is planned. Insertion of pedicle screws adjacent to the hemivertebra. The posterior elements of the hemivertebra are removed: lamina, joint facets, pedicle, transverse process. Resection of the accessory proximal rib in the thoracic spine. Following blunt dissection at the lateral and anterior surface of the hemivertebra, the body of the hemivertebra and the adjacent discs are resected. The resulting gap is closed by compression via transpedicular instrumentation thus correcting the scoliotic deformity. In case of synostosis or contralateral bar formation, the concave side of the spine is dissected and the synostosis osteomized.
POSTOPERATIVE MANAGEMENT
Early mobilization on postoperative day 1. Bracing for 12 weeks depending on stability of the instrumentation. Periodic clinical and radiographic controls until the end of growth.
RESULTS
Posterior hemivertebra resection with transpedicular instrumentation is considered as the standard treatment of congenital scoliosis. Correction rates of 60-80% are achieved. Cervical and lumbosacral hemivertebrae may require an additional anterior approach. In case of synostosis, bar formation, or rib synostosis, further corrective surgeries may be necessary during growth.
Topics: Humans; Scoliosis; Treatment Outcome; Spinal Fusion; Spine; Synostosis; Retrospective Studies; Follow-Up Studies; Thoracic Vertebrae
PubMed: 37725190
DOI: 10.1007/s00064-023-00827-5 -
Foot & Ankle International Aug 2023The spring ligament is one of the main stabilizers of the medial arch of the foot and the primary static supporter of the talonavicular joint. Attenuation or rupture of... (Review)
Review
The spring ligament is one of the main stabilizers of the medial arch of the foot and the primary static supporter of the talonavicular joint. Attenuation or rupture of this ligament is thought to play a central role in the pathophysiology of progressive collapsing foot deformity. Traditional correction of flexible flatfoot consists of posterior tibial tendon augmentation along with various osteotomies or hindfoot fusions. Repair or reconstruction of the spring ligament has not been as widely pursued. In recent years, newer techniques have been explored and may improve outcomes of traditional procedures, or possibly entirely replace some osteotomies. Combined spring-deltoid ligament reconstruction is also gaining traction as a viable technique, particularly as the ankle begins to deform into valgus. This review summarizes the variety of nonanatomic and anatomic reconstruction techniques that have been described, including autologous tendon transfers, allografts, and synthetic augmentation. Although many have only been characterized in biomechanical cadaver studies, this article reviews preliminary clinical studies that have shown promising results. There is a need for more high-quality studies evaluating the clinical, radiographic, and patient-reported outcomes following spring ligament reconstruction.
Topics: Humans; Foot; Flatfoot; Ligaments, Articular; Foot Deformities, Acquired; Tendon Transfer
PubMed: 37341112
DOI: 10.1177/10711007231178538