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European Journal of Medical Genetics Feb 2024Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these...
Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; Anophthalmos; Microphthalmos; Heart Defects, Congenital; Limb Deformities, Congenital; CHARGE Syndrome; Prevalence
PubMed: 38110175
DOI: 10.1016/j.ejmg.2023.104892 -
Annual Review of Medicine Jan 2024Congenital heart disease (CHD), a heterogeneous group of structural abnormalities of the cardiovascular system, is the most frequent cause of severe birth defects.... (Review)
Review
Congenital heart disease (CHD), a heterogeneous group of structural abnormalities of the cardiovascular system, is the most frequent cause of severe birth defects. Related to improved pediatric outcomes, there are now more adults living with CHD, including complex lesions, than children. Adults with CHD are at high risk for complications related to their underlying anatomy and past surgical palliative interventions. Adults with CHD require close monitoring and proactive management strategies to improve outcomes.
Topics: Adult; Humans; Heart Defects, Congenital
PubMed: 38285514
DOI: 10.1146/annurev-med-050922-052324 -
Frontiers in Endocrinology 2023Noonan, Costello and Cardio-facio-cutaneous syndromes belong to a group of disorders named RASopathies due to their common pathogenetic origin that lies on the Ras/MAPK... (Review)
Review
Noonan, Costello and Cardio-facio-cutaneous syndromes belong to a group of disorders named RASopathies due to their common pathogenetic origin that lies on the Ras/MAPK signaling pathway. Genetics has eased, at least in part, the distinction of these entities as they are presented with overlapping clinical features which, sometimes, become more pronounced with age. Distinctive face, cardiac and skeletal defects are among the primary abnormalities seen in these patients. Skeletal dysmorphisms range from mild to severe and may include anterior chest wall anomalies, scoliosis, kyphosis, short stature, hand anomalies, muscle weakness, osteopenia or/and osteoporosis. Patients usually have increased serum concentrations of bone resorption markers, while markers of bone formation are within normal range. The causative molecular defects encompass the members of the Ras/MAPK/ERK pathway and the adjacent cascades, important for the maintenance of normal bone homeostasis. It has been suggested that modulation of the expression of specific molecules involved in the processes of bone remodeling may affect the osteogenic fate decision, potentially, bringing out new pharmaceutical targets. Currently, the laboratory imprint of bone metabolism on the clinical picture of the affected individuals is not clear, maybe due to the rarity of these syndromes, the small number of the recruited patients and the methods used for the description of their clinical and biochemical profiles.
Topics: Humans; ras Proteins; Heart Defects, Congenital; Ectodermal Dysplasia; Failure to Thrive
PubMed: 37964950
DOI: 10.3389/fendo.2023.1231828 -
Orphanet Journal of Rare Diseases Apr 2024Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is...
BACKGROUND
Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is strong evidence that genetics has a role in the occurrence of microtia. This systematic review aimed to determine the genes involved and the abnormalities in microtia patients' head and neck regions.
METHODS
We used seven search engines to search all known literature on the genetic and phenotypic variables associated with the development or outcome of microtia. The identified publications were screened and selected based on inclusion and exclusion criteria and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 papers in this systematic review with phenotypic data in microtia involving 1459 patients and 30 articles containing genetic data involved in microtia.
RESULT
The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%).
CONCLUSIONS
Our systematic review shows some genes involved in the microtia development, including TCOF1, SIX2, HSPA9, GSC exon 2, FANCB, HOXA2, GSC exon 3, MARS1, and CDT1 genes. We also reveal a genotype-phenotype association in microtia. In addition, further studies with more complete and comprehensive data are needed, including patients with complete data on syndromes, phenotypes, and genotypes.
Topics: Humans; Congenital Microtia; Homeodomain Proteins; Ear; Phenotype; Syndrome; Genetic Association Studies
PubMed: 38594752
DOI: 10.1186/s13023-024-03142-9 -
Archivos de Cardiologia de Mexico Sep 2023The anomalous aortic origin of the coronary arteries has an estimated prevalence of 0.02-5.7%. It can be associated with sudden death when it has an interarterial or...
INTRODUCTION
The anomalous aortic origin of the coronary arteries has an estimated prevalence of 0.02-5.7%. It can be associated with sudden death when it has an interarterial or intramural pathway or be damaged during interventions on the mitral, pulmonary and/or aortic annulus or percutaneous closure of an interatrial septal defect.
OBJECTIVE
To identify these patients by imaging techniques such as transthoracic color Doppler echocardiography (TTE), computed tomography (CT) multislice angiography or coronary angiography.
METHODS
The imaging techniques used for the detection of coronary anomalies were TTE, multislice coronary angiography or coronary angiography according to what is generally accepted.
RESULTS
Fifteen patients were identified; in 12 of them the suspicion was due to TTE and in the remaining 3, CT multislice angiography was diagnostic. The circumflex artery was the coronary artery most involved, associated or not with another coronary anomaly (12/15 patients) and in the other three cases, the anomalous coronary artery had an interarterial course, with the right coronary arteries and the anterior descending coronary arteries being involved.
CONCLUSIONS
The under diagnosis by TTE of coronary artery abnormalities may be due to the difficulty of visualization that is accentuated with age. Their detection is crucial because they can both, lead to sudden death associated with an intramural and/or interarterial pathway and complicate an interventional procedure on the interatrial septum or within the mitral, pulmonary and/or aortic rings.
Topics: Humans; Coronary Vessel Anomalies; Aorta; Tomography, X-Ray Computed; Coronary Angiography; Death, Sudden
PubMed: 37669688
DOI: 10.24875/ACM.22000136 -
Pediatric Nephrology (Berlin, Germany) Feb 2024Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common birth defects worldwide and a major cause of kidney failure in children.... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common birth defects worldwide and a major cause of kidney failure in children. Extra-renal manifestations are also common. This study reviewed diseases associated with the Genomics England CAKUT-associated gene panel for ocular anomalies. In addition, each gene was examined for expression in the human retina and an ocular phenotype in mouse models using the Human Protein Atlas and Mouse Genome Informatics databases, respectively. Thirty-four (54%) of the 63 CAKUT-associated genes (55 'green' and 8 'amber') had a reported ocular phenotype. Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract. Seven of the CAKUT-associated genes studied (11%) had no reported ocular features but were expressed in the human retina or had an ocular phenotype in a mouse model, which suggested further possibly-unrecognised abnormalities. About one third of CAKUT-associated genes (18, 29%) had no ocular associations and were not expressed in the retina, and the corresponding mouse models had no ocular phenotype. Ocular abnormalities in individuals with CAKUT suggest a genetic basis for the disease and sometimes indicate the affected gene. Individuals with CAKUT often have ocular abnormalities and may require an ophthalmic review, monitoring, and treatment to preserve vision.
Topics: Child; Mice; Animals; Humans; Kidney; Urinary Tract; Vesico-Ureteral Reflux; Urogenital Abnormalities
PubMed: 37468646
DOI: 10.1007/s00467-023-06068-9 -
Cardiovascular Pathology : the Official... 2024Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, with an incidence of approximately 1%. It can be silent and associated with normal valve... (Review)
Review
Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, with an incidence of approximately 1%. It can be silent and associated with normal valve function. However, a series of complications, even catastrophic, may occur with time: valve incompetence, valve stenosis by dystrophic calcification, infective endocarditis, progressive dilatation of the ascending aorta, aortic dissection, sudden death. The problem of BAV is not just about the number of semilunar cusps, but also the aortic wall. Severe noninflammatory degenerative changes (elastic fiber fragmentation, smooth muscle cells death, mucoid extracellular matrix accumulation=MEMA) are observed in the aortic wall of BAV patients, with intrinsic weakness accounting for progressive aneurysmal dilatation of the ascending aorta, valve incompetence, and wall dissection. The link between valve and aortic wall pathology finds most probably an explanation in the embryology of the arterial pole since neurocrestal cells play a role in the development of both the ascending aorta, aortic arch, and semilunar valves. The frequent association of adult aortic coarctation and BAV provides evidence for this hypothesis. BAV has a significant genetic component as to require screening of first-degree relatives, as outlined by AHA/ACC 2022 guidelines.
Topics: Humans; Bicuspid Aortic Valve Disease; Aortic Valve; Heart Valve Diseases; Risk Factors; Prognosis
PubMed: 38253300
DOI: 10.1016/j.carpath.2024.107604 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Dec 2023At present, there is no unified gold standard for the treatment of laryngeal clefts. Type Ⅰ laryngeal clefts with mild symptoms can be treated conservatively, such as... (Review)
Review
At present, there is no unified gold standard for the treatment of laryngeal clefts. Type Ⅰ laryngeal clefts with mild symptoms can be treated conservatively, such as thick diet feeding and using proton pump inhibitor to control reflux, while Ⅱ-Ⅳ laryngeal clefts mostly requires surgical intervention.There are many different surgical methods for the treatment of laryngeal clefts, including injection laryngoplasty, endoscopic surgical repair of laryngeal clefts and open laryngoplasty through anterior cervical approach. How to choose a more suitable surgical plan for children is a problem worth discussing. This article will review the literature on the surgical treatment of laryngeal clefts both domestically and internationally, and summarize the current situation and challenges of surgical treatment of laryngeal clefts.
Topics: Child; Humans; Congenital Abnormalities; Endoscopy; Laryngoplasty; Laryngoscopy; Larynx
PubMed: 38114316
DOI: 10.13201/j.issn.2096-7993.2023.12.010 -
BMC Medical Genomics Apr 2024Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies,...
BACKGROUND
Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes.
METHODS
The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment.
RESULTS
A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation.
CONCLUSIONS
Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.
Topics: Humans; Male; Female; Taiwan; Ciliopathies; Child; Child, Preschool; Mutation; Exome Sequencing; Bardet-Biedl Syndrome; Adolescent; Infant; Abnormalities, Multiple; Retina; Syndrome; Cilia; Eye Abnormalities; Cerebellum; Proteins; Kidney Diseases, Cystic
PubMed: 38671463
DOI: 10.1186/s12920-024-01880-0 -
Acta Obstetricia Et Gynecologica... Jun 2024Accessory cavitated uterine malformation (ACUM) is a relatively recent term used to describe a noncommunicating, accessory uterine cavity. ACUM have been published under... (Review)
Review
INTRODUCTION
Accessory cavitated uterine malformation (ACUM) is a relatively recent term used to describe a noncommunicating, accessory uterine cavity. ACUM have been published under different terms ranging from juvenile cystic adenomyosis to "uterus-like mass". The objective of this study was to systematically identify all cases of ACUM and definitions described in the literature, regardless of label, and identify morphological, epidemiological, and clinical characteristics as well as management, while also highlighting knowledge gaps.
MATERIAL AND METHODS
A systematic literature search of three databases was performed, reviewing all records of cystic myometrial lesions. Cases that fitted common definitions for ACUM were included and clinical and imaging characteristics were documented in detail. This work was registered to PROSPERO and reporting followed PRISMA guidelines for scoping reviews.
RESULTS
A total of 53 articles were included, comprising 115 cases that met the minimal criteria for ACUM. The median age at onset of symptoms was 17 years, presenting with dysmenorrhea soon after menarche. A total of 19 women were parous. On ultrasound, ACUM appears as unilocular myometrial cysts, usually with ground-glass content. Hemorrhagic content is also observed on magnetic resonance imaging (MRI), with high signal intensity on both T2 and T1-weighted images. Ninety-five (83%) cases were managed surgically, with a trend towards primary nonsurgical options. Although no adverse outcomes were reported, long-term follow-up on subsequent fertility and pregnancy was rare.
CONCLUSIONS
Despite its increasing recognition as a clinical entity, ACUM often remains underdiagnosed as it shares similarities with other myometrial masses. We propose a unified terminology and definition for ACUM based on the data in this review. ACUM presents as a cavitated lesion, surrounded by a myometrial mantle, in continuity with the anterolateral uterine wall and located beneath the insertion of the round ligament and the interstitial portion of the fallopian tube. In contrast to other uterine abnormalities, a normal uterine cavity is visualized. Future studies are needed, using a clear definition for ACUM, and prospectively investigating management strategies, including long-term follow-up of patient-reported symptoms, fertility, and pregnancy outcomes.
Topics: Humans; Female; Uterus; Urogenital Abnormalities; Magnetic Resonance Imaging
PubMed: 38345425
DOI: 10.1111/aogs.14801