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The Annals of Thoracic Surgery Jul 2023Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from... (Review)
Review
Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.
Topics: Adult; Child; Humans; Aorta, Thoracic; Heart Defects, Congenital; Aorta; International Classification of Diseases; Specialization; Aortic Valve
PubMed: 37294261
DOI: 10.1016/j.athoracsur.2023.03.023 -
Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
Prenatal Diagnosis Feb 2024The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a... (Review)
Review
OBJECTIVE
The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition.
METHODS
A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex.
RESULTS
We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes.
CONCLUSION
Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA.
Topics: Pregnancy; Female; Humans; Kidney; Kidney Diseases; Urogenital Abnormalities; Chromosome Aberrations; Syndrome; Congenital Abnormalities
PubMed: 38180355
DOI: 10.1002/pd.6516 -
Journal of Assisted Reproduction and... May 2024The purpose of this narrative review was to assess the limited literature on fetal anomalies diagnosed in the second trimester of pregnancy and parental decision-making... (Review)
Review
PURPOSE
The purpose of this narrative review was to assess the limited literature on fetal anomalies diagnosed in the second trimester of pregnancy and parental decision-making and identify sources of information deemed as facilitators and barriers to medical decisions.
METHODS
This was a literature review of source material and information about fetal anomalies diagnosed in the second trimester of pregnancy, decision-making, decision tools or aids, and sources of information for anomalies. The search string used explored related peer-reviewed publications and systematic reviews between 2007 and 2024. We also reviewed references from publications meeting inclusion criteria. The search was conducted between June 2022 and February 2024. Exclusion criteria included conference abstracts, non-peer reviewed literature, and articles not available in English language. A total of 77 publications were identified by searching multiple databases using a predefined search string. The search encompassed full text articles from 2007 to 2024 and 11 full-text publications were ultimately included in the review. A list of 45 co-occurring keywords was generated from the included texts, with each keyword having a minimum of two co-occurrences.
RESULTS
Key themes identified included (1) the role of the clinician and need for development of professional knowledge and empathy surrounding discussion of fetal anomalies with patients; (2) information gathering, with individuals reporting use of multiple strategies to obtain information; while the majority found information satisfying, they preferred more details on diagnosis, long-term outcomes of the fetus/child and management of the pregnancy or termination process; and (3) decision-making, the path and process of how individuals made decisions about the pregnancy including quality of life, future fertility, and seeking other people's experiences.
CONCLUSION
Many factors contribute to an individual's decision-making after a diagnosis of a fetal anomalies diagnosed in the second trimester of pregnancy, ranging from personal beliefs and goals to shared experiences of others and access to care. Understanding how sources of information may be deemed both as facilitators and barriers to different individuals during the decision-making process is important for healthcare providers in order to understand how to most effectively support patients. There is a dearth of information on training healthcare professionals to provide support to patients facing these decisions.
Topics: Humans; Pregnancy; Female; Congenital Abnormalities; Decision Making; Prenatal Diagnosis; Pregnancy Trimester, Second
PubMed: 38630201
DOI: 10.1007/s10815-024-03112-x -
Nature Genetics Dec 2023Identifying genes linked to extreme phenotypes in humans has the potential to highlight biological processes not shared with all other mammals. Here, we report the...
Identifying genes linked to extreme phenotypes in humans has the potential to highlight biological processes not shared with all other mammals. Here, we report the identification of homozygous loss-of-function variants in the primate-specific gene ZNF808 as a cause of pancreatic agenesis. ZNF808 is a member of the KRAB zinc finger protein family, a large and rapidly evolving group of epigenetic silencers which target transposable elements. We show that loss of ZNF808 in vitro results in aberrant activation of regulatory potential contained in the primate-specific transposable elements it represses during early pancreas development. This leads to inappropriate specification of cell fate with induction of genes associated with liver identity. Our results highlight the essential role of ZNF808 in pancreatic development in humans and the contribution of primate-specific regions of the human genome to congenital developmental disease.
Topics: Animals; Humans; Cell Differentiation; DNA Transposable Elements; Genome, Human; Primates; DNA-Binding Proteins; Congenital Abnormalities; Pancreas
PubMed: 37973953
DOI: 10.1038/s41588-023-01565-x -
Pediatric Nephrology (Berlin, Germany) Dec 2023Congenital anomalies of the kidney and urinary tract (CAKUT) result from disruptions in normal kidney and urinary tract development during fetal life and collectively... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) result from disruptions in normal kidney and urinary tract development during fetal life and collectively represent the most common cause of kidney failure in children worldwide. The antenatal determinants of CAKUT are diverse and include mutations in genes responsible for normal nephrogenesis, alterations in maternal and fetal environments, and obstruction within the normal developing urinary tract. The resultant clinical phenotypes are complex and depend on the timing of the insult, the penetrance of underlying gene mutations, and the severity and timing of obstruction related to the sequence of normal kidney development. Consequently, there is a broad spectrum of outcomes for children born with CAKUT. In this review, we explore the most common forms of CAKUT and those most likely to develop long-term complications of their associated kidney malformations. We discuss the relevant outcomes for the different forms of CAKUT and what is known about clinical characteristics across the CAKUT spectrum that are risk factors of long-term kidney injury and disease progression.
Topics: Child; Female; Humans; Pregnancy; Kidney; Urinary Tract; Urogenital Abnormalities; Risk Factors; Disease Progression
PubMed: 36867265
DOI: 10.1007/s00467-023-05899-w -
Archives of Gynecology and Obstetrics Jun 2024Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also... (Review)
Review
PURPOSE
Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring.
METHODS
This is a narrative review based on scientific and review articles on the matter.
RESULTS
Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring.
CONCLUSION
It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.
Topics: Humans; Pregnancy; Female; Pregnancy Complications; Infant, Newborn; Obesity; Prenatal Exposure Delayed Effects; Pregnancy Outcome; Obesity, Maternal; Diabetes, Gestational; Congenital Abnormalities
PubMed: 38502190
DOI: 10.1007/s00404-023-07349-2 -
American Journal of Medical Genetics.... Sep 2023Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in...
Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in the reported studies. The aims of this report was to study the types and the prevalence of the anomalies co-occurring with PRS in a well-studied population northeastern France. The types and the prevalence of anomalies co-occurring in cases with PRS were ascertained in all terminations of pregnancy, stillbirths and live births in 387,067 births occurring consecutively during the period 1979-2007 in the area covered by our registry of congenital anomalies which is population-based, 89 cases of PRS were registered during the study period with a prevalence of 2.29 per 10,000 births, 69.7% of the cases had associated non-PRS anomalies. Chromosomal abnormalities were present in 10 (11.2%) cases including three 22 q11.2 deletion. Non-chromosomal recognizable conditions were diagnosed in 27 cases (30.3%) including 10 Stickler syndrome, 8 Treacher Collins syndrome, 3 cases with short stature and 6 other syndromes. Multiple congenital anomalies (MCA) were present in 25 cases (28.1%). The most frequent MCA were in the ear, face and neck (35 out of 98 anomalies, 35.7%), cardiovascular (18 anomalies, 18.4%), musculoskeletal (11 anomalies, 11.2%), central nervous (7 anomalies, 7.1%), urinary (6 anomalies, 6.1%), and eye (6 anomalies, 6.1%) system. The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with PRS.
Topics: Pregnancy; Female; Humans; Pierre Robin Syndrome; Abnormalities, Multiple; Chromosome Aberrations; Connective Tissue Diseases; France
PubMed: 37477275
DOI: 10.1002/ajmg.a.63344 -
HGG Advances Jul 2023Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or...
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was used to further reproduce findings in diverse genetic backgrounds. Proband and OMIM phenotypes annotated using the Human Phenotype Ontology were analyzed to quantitatively delineate the phenotypic spectrum associated with variant alleles found in our MRKH cohort and those previously published. This study reports 18 novel variant alleles, 16 within a multiethnic MRKH cohort and two within a congenital scoliosis cohort. Cohort-wide analyses for a burden of rare variants within a single gene identified likely damaging variants in (MIM: 617782), a known disease gene for renal hypoplasia and uterine abnormalities (MIM: 617805), in 16 of 590 MRKH probands. variant alleles, including a CNV null allele, were found in 8 MRKH type 1 probands and 8 MRKH type II probands. This study used quantitative phenotypic analyses in a worldwide multiethnic cohort to identify and strengthen the association of to isolated uterine agenesis (MRKH type I) and syndromic MRKH type II.
Topics: Female; Humans; 46, XX Disorders of Sex Development; Urogenital Abnormalities; Uterus
PubMed: 37124138
DOI: 10.1016/j.xhgg.2023.100188 -
Otolaryngology--head and Neck Surgery :... Jul 2024Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs. (Comparative Study)
Comparative Study
OBJECTIVE
Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs.
STUDY DESIGN
Retrospective cohort study.
SETTING
Tertiary care pediatric hospital.
METHODS
Pediatric patients who underwent robotic or traditional (open or endoscopic) LC repair between 2010 and 2021 were identified. Patient characteristics, operative times, adverse events, hospital length of stay (LOS), and modified barium swallow study (MBSS) results were compared.
RESULTS
Eighteen robotic and thirty traditional LC repairs were identified. Mean surgical (149 vs 111 min, P < .05) and OR times (207 vs 139 min, P < .002) were increased for robotic type I LC repairs, but were similar for type II and III LC. Mean hospital LOS was increased for robotic type I LC repairs (2.6 vs 1.2 days, P < .006), but was decreased for type II (4 vs 12.2 days) and type III (4.3 vs 94.5 days) LC. Postoperative MBSS results were improved for robotic type I LC repairs at 12 months (82% vs 43%, P = .05), and trended toward improvement at 6 months for type II (75% vs 22%), and type III (67% vs 50%) LC repairs, although significance was limited for type II and III LC due to the number of subjects. A robotic approach was used successfully to revise all recurrent LC that failed traditional repairs.
CONCLUSION
Robotic type 1 LC repairs demonstrated increased operative times and hospital LOS but improved postoperative swallow outcomes compared to traditional approaches may be particularly useful in cases of recurrent clefts.
Topics: Humans; Retrospective Studies; Robotic Surgical Procedures; Male; Female; Larynx; Infant; Child, Preschool; Length of Stay; Treatment Outcome; Congenital Abnormalities; Operative Time; Child
PubMed: 38488232
DOI: 10.1002/ohn.723