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Nature Reviews. Nephrology Dec 2015Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a spectrum of structural renal malformations and are the leading cause of end-stage renal disease... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a spectrum of structural renal malformations and are the leading cause of end-stage renal disease in children. The genetic diagnosis of CAKUT has proven to be challenging due to genetic and phenotypic heterogeneity and incomplete genetic penetrance. Monogenic causes of CAKUT have been identified using different approaches, including single gene screening, and gene panel and whole exome sequencing. The majority of the identified mutations, however, lack substantial evidence to support a pathogenic role in CAKUT. Copy number variants or single nucleotide variants that are associated with CAKUT have also been identified. Numerous studies support the influence of epigenetic and environmental factors on kidney development and the natural history of CAKUT, suggesting that the pathogenesis of this syndrome is multifactorial. In this Review we describe the current knowledge regarding the genetic susceptibility underlying CAKUT and the approaches used to investigate the genetic basis of CAKUT. We outline the associated environmental risk factors and epigenetic influences on CAKUT and discuss the challenges and strategies used to fully address the involvement and interplay of these factors in the pathogenesis of the disease.
Topics: Congenital Abnormalities; Environmental Exposure; Epigenesis, Genetic; Humans; Kidney; Urinary Tract
PubMed: 26281895
DOI: 10.1038/nrneph.2015.140 -
Journal of Obstetrics and Gynaecology... Dec 2019
Topics: Canada; Congenital Abnormalities; Female; Fetal Diseases; Fetoscopy; Forecasting; History, 20th Century; History, 21st Century; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 31785675
DOI: 10.1016/j.jogc.2019.08.039 -
World Neurosurgery Jun 2020Caudal regression syndrome (CRS) represents a spectrum of clinical phenotypes with varying degrees of malformation of the lower body with involvement of structures... (Review)
Review
Caudal regression syndrome (CRS) represents a spectrum of clinical phenotypes with varying degrees of malformation of the lower body with involvement of structures deriving from all 3 layers of the trilaminar embryo. We review areas of active investigation in the diagnosis, etiology, epidemiology, and treatment of the disease with a focus on underlying genetics. CRS pathobiology is complex and multifactorial with a significant contribution from environmental factors as evidenced in twin studies. Contemporary genomic and genetic investigations in both human primary tissue and murine in vitro and in vivo models implicate various genes associated with caudal differentiation and neural cell migration in embryogenesis. A large number of identified targets center around the metabolic regulation of retinoic acid and its derivatives. Dysregulation of retinoic acid homeostasis has been associated with abnormal embryonic cell migration, differentiation, and organogenesis with resulting malformations and agenesis in both a laboratory and a clinical setting. There appears to be a significant overlap in potential genetic targets with CRS and other developmental syndromes with similar presentations, such as VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association. CRS represents a spectrum of caudal developmental abnormalities with treatment options limited to mild and moderate expressions of disease. Continued research is necessary to further clarify mechanisms of disease pathobiology and complex polygenetic and environmental interaction. Despite this, progress has been made in identifying genetic targets and downstream effectors contributing to preclinical and clinical progression.
Topics: Abnormalities, Multiple; Animals; Genomics; Humans; Limb Deformities, Congenital; Nervous System Malformations; Tretinoin
PubMed: 32200015
DOI: 10.1016/j.wneu.2020.03.057 -
Clinical Otolaryngology : Official... Mar 2019
Topics: Child, Preschool; Congenital Abnormalities; Deglutition Disorders; Humans; Infant; Larynx
PubMed: 30188606
DOI: 10.1111/coa.13223 -
Foot and Ankle Clinics Sep 2014Patients with a preexisting hindfoot deformity, who undergo resection (with or without soft tissue interposition) of a tarsal coalition, may present with recurrent pain... (Review)
Review
Patients with a preexisting hindfoot deformity, who undergo resection (with or without soft tissue interposition) of a tarsal coalition, may present with recurrent pain and worsening planovalgus deformity. This is due to the secondary effect of soft tissue contractures (lateral ligaments, peroneal tendons, calf muscles) "pulling" the foot into more valgus. Physiotherapy and insoles may help some patients. Depending on the flexibility of the hindfoot and the presence or otherwise of joint degeneration, joint-preserving corrective procedures or corrective joint fusions may be needed. Gastrocnemius, Achilles, and/or peroneal tendon releases may be required, to avoid equinus or further recurrence.
Topics: Flatfoot; Foot Deformities, Congenital; Radiography; Tarsal Bones
PubMed: 25129361
DOI: 10.1016/j.fcl.2014.06.011 -
The Veterinary Clinics of North... Aug 2017Early recognition and treatment of congenital and acquired flexural deformities of the carpi and fetlocks of foals can lead to conformation correction and an athletic... (Review)
Review
Early recognition and treatment of congenital and acquired flexural deformities of the carpi and fetlocks of foals can lead to conformation correction and an athletic future. Treatment is often based on rigid external coaptation assisted by systemic medical treatment. Foals that readily respond to treatment and correct conformation faults can have normal adult athletic expectations.
Topics: Animals; Animals, Newborn; Carpus, Animal; Horse Diseases; Horses; Joint Deformities, Acquired; Limb Deformities, Congenital
PubMed: 28551286
DOI: 10.1016/j.cveq.2017.03.004 -
Molecular Genetics and Genomics : MGG Sep 2022Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited...
Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.
Topics: Brachydactyly; Clubfoot; Humans; Limb Deformities, Congenital; Molecular Biology; Polydactyly; Syndactyly
PubMed: 35907958
DOI: 10.1007/s00438-022-01930-1 -
Indian Journal of Pediatrics Dec 2015Thoraco-abdominal viscera have unique morphological asymmetry, unlike the body's external organs. Heterotaxy syndrome is a disorder in which there is a loss of normal... (Review)
Review
Thoraco-abdominal viscera have unique morphological asymmetry, unlike the body's external organs. Heterotaxy syndrome is a disorder in which there is a loss of normal left to right asymmetry of thoraco-abdominal viscera and their naturally proscribed spatial relationship. It has multiple anatomical alterations, culminating into physiological and hemodynamic consequences. It is divided into two groups on the basis of morphology of the two atrial appendages. These subgroups are - 1) Isomerism of right atrial appendage (asplenia syndrome); 2) Isomerism of left atrial appendage (polysplenia syndrome); Patients from group I, usually have severe cardiac malformations and present early. They may have duct dependent lesions and eventually may undergo Fontan surgery. However, extracardiac anomalies are more common in group II. All the patients must be evaluated in detail to rule out anomalies like gut-malrotation. Patients must be provided with special care for their susceptibility to infection due to absence of spleen or presence of splenic malfunction. Majority of these patients may have genetic link and may present in families. Hence, genetic evaluation is necessary before assuming long term outcome.
Topics: Congenital Abnormalities; Disease Management; Early Diagnosis; Hemodynamics; Heterotaxy Syndrome; Humans; Prognosis
PubMed: 26612104
DOI: 10.1007/s12098-015-1925-x -
BioMed Research International 2018In the most recent publications on Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, the uterine remnants and ovaries in patients may develop uterine remnant leiomyoma,... (Review)
Review
In the most recent publications on Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, the uterine remnants and ovaries in patients may develop uterine remnant leiomyoma, adenomyosis, or ovarian tumor, and this can lead to problems in differential diagnosis. Here we summarize the diagnosis methods and available interventions for ovarian tumor in MRKH syndrome, with emphasis on the relevant clinical findings and illustrative relevant case. According to the clinical findings and illustrative relevant case, with the help of imaging techniques, ovarian tumors can be detected in the pelvis in patients with MRKH syndrome and evaluated in terms of size. Laparoscopy could further differentiate ovarian tumors into different pathological types. In addition, laparoscopic surgery not only is helpful for the diagnosis of MRKH combined ovarian tumor, but also has a good treatment role for excising ovarian tumor at the same time. Moreover, laparoscopic removals of ovarian tumor can be considered as a safe and reliable treatment for conservative management.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Laparoscopy; Mullerian Ducts; Ovarian Neoplasms
PubMed: 29721502
DOI: 10.1155/2018/2369430 -
Der Orthopade Jul 2016Many congenital malformations of the hand and forearm, e. g. polydactyly, thumb duplication, syndactyly and radial aplasia, are already evident at birth and newborns... (Review)
Review
Many congenital malformations of the hand and forearm, e. g. polydactyly, thumb duplication, syndactyly and radial aplasia, are already evident at birth and newborns are promptly referred to specialized departments. In contrast, orthopedic surgeons are often confronted with malformations of the hand and forearm, which gradually become clinically conspicuous during growth. This review article focuses on these specific malformations, which regularly upset the patients in practice and in most cases the parents even more so. In addition to the diagnostics and differential diagnostics, the conservative and surgical treatment options are presented.
Topics: Diagnosis, Differential; Female; Forearm; Hand Deformities, Congenital; Humans; Immobilization; Infant, Newborn; Male; Plastic Surgery Procedures
PubMed: 27300693
DOI: 10.1007/s00132-016-3282-5