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JPMA. the Journal of the Pakistan... Feb 2024Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare entity. It most commonly affects the tubular bones leading to dwarfism and a long...
Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare entity. It most commonly affects the tubular bones leading to dwarfism and a long trunk with ossification defects. Other presentations are wide hands and feet, dysplastic nails, thin hair, and cardiac malformations. An eight-year-old female patient presented to our tertiary care centre with complaints of short stature, abnormal dentition, and fatigue. The child's parents were first-degree relatives. On radiological imaging, it was revealed that the patient had postaxial polydactyly, short stature, and genu valgum deformity along with mild cardiomegaly. All these features were indicative of Ellis-van Creveld syndrome. EVC is a rare clinical syndrome with a distinctive clinical presentation. It requires comprehensive radiological investigations and the management is best done with a multidisciplinary approach.
Topics: Female; Child; Humans; Ellis-Van Creveld Syndrome; Polydactyly; Heart Defects, Congenital; Fingers
PubMed: 38419244
DOI: 10.47391/JPMA.7049 -
PLoS Genetics Nov 2023Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as...
Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST). We show that ST can be used to investigate the transcriptome of the developing arterial valves, circumventing the problems of accurately dissecting out these tiny structures from the developing embryo. We show that the transcriptome of CS16 and CS19 arterial valves overlap considerably, despite being several days apart in terms of human gestation, and that expression data confirm that the great majority of the most differentially expressed genes are valve-specific. Moreover, we show that the transcriptome of the human arterial valves overlaps with that of mouse atrioventricular valves from a range of gestations, validating our dataset but also highlighting novel genes, including four that are not found in the mouse genome and have not previously been linked to valve development. Importantly, our data suggests that valve transcriptomes are under-represented when using commonly used databases to filter for genes important in cardiac development; this means that causative variants in valve-related genes may be excluded during filtering for genomic data analyses for, for example, BAV. Finally, we highlight "novel" pathways that likely play important roles in arterial valve development, showing that mouse knockouts of RBP1 have arterial valve defects. Thus, this study has confirmed the utility of ST for studies of the developing heart valves and broadens our knowledge of the genes and signalling pathways important in human valve development.
Topics: Humans; Mice; Animals; Heart Valve Diseases; Aortic Valve; Bicuspid Aortic Valve Disease; Gene Expression Profiling; Transcriptome
PubMed: 38011284
DOI: 10.1371/journal.pgen.1010777 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Oct 2023The long-term effect of muscular force balance reconstruction technique combined with intranasal fixation for correcting secondary nasolabial deformity after unilateral...
OBJECTIVES
The long-term effect of muscular force balance reconstruction technique combined with intranasal fixation for correcting secondary nasolabial deformity after unilateral cleft lip was evaluated. The aim was to provide a basis for further improving the surgical treatment effect of secondary nasolabial deformity of acleft lip.
METHODS
A total of 40 patients aged 4-28 years with secondary nasal deformity and unilateral cleft lip were selected as research subjects. The two-dimensional photo measurement analysis method was used in comparing the surgical results before and immediately after the operation (7 d) and 1 year after the operation.
RESULTS
Columellar angle, nostril height ratio (NHR), alar rim angle, alar rim angle ratio, and nostril shape (NS) increased dimmediately after the operation, whereas alar base width ratio (ABWR) and nostril width ratio decreased (NHR) immediately after the operation (<0.01). The ABWR, NHR, and NS immediately after the operation were not significantly different from those 1 year after the operation (>0.05).
CONCLUSIONS
Muscular force balance reconstruction technique combined with intranasal fixation is effective in the repair of unilateral secondary nasolabial deformity, and stable results can be obtained 1 year after surgery.
Topics: Humans; Cleft Lip; Nose; Rhinoplasty; Treatment Outcome
PubMed: 37805680
DOI: 10.7518/hxkq.2023.2023136 -
Revista Espanola de Enfermedades... Jan 2024Abernethy syndrome (AS or extrahepatic portosystemic shunt) is an uncommon congenital malformation consisting of agenesis or hypoplasia of the portal vein (PV) in such a...
Abernethy syndrome (AS or extrahepatic portosystemic shunt) is an uncommon congenital malformation consisting of agenesis or hypoplasia of the portal vein (PV) in such a way that splanchnic venous blood drains directly into the systemic circulation through aberrant communications, resulting in a portosystemic shunt that bypasses the liver AS is an underdiagnosed condition with unknown incidence and complication rate given that symptoms are usually absent. AS identification is increasingly common because of improved imaging techniques, hence prognostic implications and clinical management need be understood. This editorial reviews the natural history of AS and its diagnostic-therapeutic implications, illustrating the process with a series of cases from our institution.
Topics: Humans; Liver Neoplasms; Vascular Malformations; Portal Vein; Portasystemic Shunt, Surgical; Syndrome
PubMed: 37522317
DOI: 10.17235/reed.2023.9781/2023 -
The Journal of Craniofacial Surgery Oct 2023The pharyngeal arches form the cornerstone of the complex anatomy of the face and neck. These embryologic structures are the foundation of face and neck development, and...
The pharyngeal arches form the cornerstone of the complex anatomy of the face and neck. These embryologic structures are the foundation of face and neck development, and anomalous growth can result in craniofacial abnormalities. Surgeons who manage head and neck pathology and pathoanatomy will invariably encounter conditions associated with aberrant pharyngeal arch anatomy, and a thorough understanding of the normal and pathological development of these important structures is paramount to accurate diagnosis and treatment. This manuscript is the first of a three-part educational series that addressed the pharyngeal/branchial arch embryology, development, nomenclature, and normal anatomy (Part I), pathologic anomalies of ear and neck derived from abnormal development of the arches (Part II), and different types of orofacial clefts, including Tessier clefts (Part III).
Topics: Humans; Branchial Region; Cleft Lip; Cleft Palate; Head; Neck
PubMed: 37264513
DOI: 10.1097/SCS.0000000000009374 -
Journal of Clinical Research in... Nov 2023Patients with congenital adrenal hyperplasia (CAH) require lifelong therapy with glucocorticoids to suppress androgen excess and substitute for deficient cortisol. An... (Observational Study)
Observational Study
OBJECTIVE
Patients with congenital adrenal hyperplasia (CAH) require lifelong therapy with glucocorticoids to suppress androgen excess and substitute for deficient cortisol. An important aspect of care is the prevention of metabolic sequelae. In infants, potentially lethal nocturnal hypoglycaemia has been described. In adolescence, visceral obesity, hypertension, hyperinsulinism and insulin resistance are reported. To date, systematic studies of glucose profiles in this age group with CAH are lacking.
METHODS
This was a monocentric, prospective, observational study to determine the glucose profiles under different treatment regimens in a cohort of young patients with CAH. The continuous glucose monitoring device used was the latest generation FreeStyle Libre 3 sensor in blinded mode. Therapeutic and auxological data were obtained.
RESULTS
The cohort consisted of 10 children/adolescents with a mean age of 11 years. Three patients exhibited morning fasting hyperglycaemia. Overall, 6 out of 10 patients had unacceptably few total values in the desired range of 70-120 mg/dL. Tissue glucose values above 140-180 mg/dL were found in 5 of 10 patients. The mean value for glycosylated haemoglobin for the cohort was of 5.8%. All pubertal adolescents with reverse circadian regimens had significantly higher glucose levels at night. Two adolescents showed asymptomatic nocturnal hypoglycaemia.
CONCLUSION
Most of the patients exhibited abnormalities in glucose metabolism. Two-thirds had elevated total 24h glucose values outside the age-appropriate reference values. Thus, this aspect may need to be addressed early in life by adjusting the doses, treatment regimen or dietary measures. Consequently, reverse circadian therapy regimens should be critically indicated and closely monitored due to the potential metabolic risk.
Topics: Infant; Humans; Child; Adolescent; Adrenal Hyperplasia, Congenital; Blood Glucose; Prospective Studies; Blood Glucose Self-Monitoring; Hydrocortisone; Hypoglycemia; Glucose
PubMed: 37218136
DOI: 10.4274/jcrpe.galenos.2023.2023-3-5 -
PloS One 2023A novel machine learning framework that is able to consistently detect, localize, and measure the severity of human congenital cleft lip anomalies is introduced. The...
A novel machine learning framework that is able to consistently detect, localize, and measure the severity of human congenital cleft lip anomalies is introduced. The ultimate goal is to fill an important clinical void: to provide an objective and clinically feasible method of gauging baseline facial deformity and the change obtained through reconstructive surgical intervention. The proposed method first employs the StyleGAN2 generative adversarial network with model adaptation to produce a normalized transformation of 125 faces, and then uses a pixel-wise subtraction approach to assess the difference between all baseline images and their normalized counterparts (a proxy for severity of deformity). The pipeline of the proposed framework consists of the following steps: image preprocessing, face normalization, color transformation, heat-map generation, morphological erosion, and abnormality scoring. Heatmaps that finely discern anatomic anomalies visually corroborate the generated scores. The proposed framework is validated through computer simulations as well as by comparison of machine-generated versus human ratings of facial images. The anomaly scores yielded by the proposed computer model correlate closely with human ratings, with a calculated Pearson's r score of 0.89. The proposed pixel-wise measurement technique is shown to more closely mirror human ratings of cleft faces than two other existing, state-of-the-art image quality metrics (Learned Perceptual Image Patch Similarity and Structural Similarity Index). The proposed model may represent a new standard for objective, automated, and real-time clinical measurement of faces affected by congenital cleft deformity.
Topics: Humans; Cleft Lip; Cleft Palate; Computer Simulation; Musculoskeletal Diseases; Machine Learning; Image Processing, Computer-Assisted
PubMed: 37535557
DOI: 10.1371/journal.pone.0288228 -
Journal of the American Heart... Mar 2024Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term...
BACKGROUND
Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth.
METHODS AND RESULTS
Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (=-0.25 to -0.31, all <0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted =0.25-0.47, all <0.05).
CONCLUSIONS
Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.
Topics: Infant, Newborn; Child; Pregnancy; Humans; Female; Placenta; Fetal Development; Brain; Heart Defects, Congenital; Fetal Diseases; Brain Injuries
PubMed: 38420785
DOI: 10.1161/JAHA.123.033189 -
The Journal of Clinical Investigation Dec 2023Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms...
Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities. Here, we found that KCTD1 and KCTD15 can form multimeric complexes and can compensate for each other's loss and that disease mutations are dominant negative, resulting in lack of KCTD1/KCTD15 function. We demonstrated that KCTD15 is critical for cardiac outflow tract development, whereas KCTD1 regulates distal nephron function. Combined inactivation of KCTD1/KCTD15 in keratinocytes resulted in abnormal skin appendages but not in ACC. Instead, KCTD1/KCTD15 inactivation in neural crest cells resulted in ACC linked to midline skull defects, demonstrating that ACC is not caused by a primary defect in keratinocytes but is a secondary consequence of impaired cranial neural crest cells, giving rise to midline cranial suture cells that express keratinocyte-promoting growth factors. Our findings explain the clinical observations in patients with KCTD1 versus KCTD15 mutations, establish KCTD1/KCTD15 complexes as critical regulators of ectodermal and neural crest cell functions, and define ACC as a neurocristopathy.
Topics: Humans; Neural Crest; Ectodermal Dysplasia; Scalp; Epidermis; Co-Repressor Proteins; Potassium Channels
PubMed: 38113115
DOI: 10.1172/JCI174138 -
La Pediatria Medica E Chirurgica :... Dec 2023Current knowledge on congenital microgastria is limited due to its extreme rarity, and the paucity of nutritional and quality of life follow-ups. Patients affected by...
Current knowledge on congenital microgastria is limited due to its extreme rarity, and the paucity of nutritional and quality of life follow-ups. Patients affected by congenital microgastria cases followed at out center were screened, and general and nutritional status were evaluated at follow-up visits through validated questionnaires. Three cases were included: one patient died because of a complex syndromic picture where microgastria was imperatively approached conservatively. The remaining cases underwent Hunt-Lawrence at 2 and 17 months. After 2 years and 27 years postoperatively, both patients are on full oral intake. The 28-yearold patient did not reach a BMI higher than 18. She rated her quality of life as unimpacted, with a Gastrointestinal Quality of Life Index of 111. In the other case, parents reported about their 2-yearold child an Infant Gastrointestinal Symptom Questionnaire of 13, corresponding to "no distress". Our findings confirm the literature trend supporting the role of early surgery in microgastria to improve outcomes. We presented the nutritional status and quality of life in two cases of congenital microgastria operated according to Hunt-Lawrence at a 2-year and 27-year distance, which is the longest follow-up reported to date.
Topics: Adult; Female; Humans; Infant; Digestive System Abnormalities; Follow-Up Studies; Quality of Life; Stomach Diseases
PubMed: 38112623
DOI: 10.4081/pmc.2023.326