Organ Malformations Research Articles

Goldenhar Syndrome: Quality-of-Life Analysis of 43 Consecutive Patients.

Goldenhar syndrome is a rare congenital disease, characterized by the malformation of craniofacial features, spine, and other organs. Its pathogenesis and impact on patients' quality of life (QoL) have not been fully elucidated as yet. Therefore, data of all patients with Goldenhar syndrome, who were treated at Hannover Medical School between 1997 and 2020, were analyzed. Forty-three patients were identified. Their medical records were carefully reviewed for data regarding their age, sex, demographics, Pruzansky classification, surgical history, and affected side. Goldenhar syndrome-associated medical conditions, therapeutic procedures, and the impact of disease on QoL were assessed. Their QoL was assessed using the Oral Health Impact Profile (OHIP)-14 questionnaire. The χ 2 test and Pearson correlation were performed for statistical evaluation. Female sex was positively correlated with OHIP outcomes, whereas male sex had a negative correlation with OHIP outcomes. Therefore, females had significantly worse QoL than males. No significant correlation was observed between the Pruzansky classification and QoL or between surgical history and QoL. Goldenhar syndrome is a rare disease that presents with varying severity. Hence, prospective studies are required to further investigate the impact of Goldenhar syndrome on the QoL.

The Effect of Cynometra cauliflora Linn. Fruit Extract-Induced Congenital Anomalies on Chick Embryos

Background: Cynometra cauliflora is a traditional folk medicine that is used to treat a variety of unpleasant symptoms without adverse effects. Previous studies have shown that C. cauliflora fruit relieving morning sickness and nausea in pregnant women. However, no research has been performed on the effect of C. cauliflora fruit extract on birth anomalies. Objective: In this study, we aim to investigate the effects of C. cauliflora fruit extract on developing chick embryos. Materials and Methods: Three hundred fertilized eggs were divided into 2 groups; 1) the experimental groups received various doses of C. cauliflora fruit extract at 50, 100, 200, and 400 mg/kg, and 2) the control group received a 0.9 % normal saline solution. One hundred and fifty eggs at embryonic day-3 (ED-3) were observed for LC50, morphology, and histology, while the 150 eggs at embryonic day-6 (ED-6) were investigated for morphology and histology. Results: At a dosage of 291.70 mg/kg, the C. cauliflora fruit extract induced mortality in ED-3 by more than 50 %. Moreover, fruit extraction can also result in anomalies in ED-3 and ED-6, such as anterior neuropore openings, heart tubes, liver and kidney tissue defects. Conclusion: As a result, it was determined that tissue damage and organ malformation followed dose-dependent and all-or-none laws. Despite having a wide range of medical properties, C. cauliflora fruit extracts have been demonstrated to impair early growth and development and cause birth abnormalities in animal studies. This will allow further determination of regulatory criteria for medical use, particularly for pregnant women. HIGHLIGHTS First report of the cauliflora fruit extract induced embryonic lethality The cauliflora fruit extract induces embryonic organ and tissue anomalies following dose-dependent and all-or-none laws These experimental protocols are beneficial for teratogenesis studies GRAPHICAL ABSTRACT

Congenital malformations of the female genital organs

Congenital malformations of the female genital organs

Challenging problems of congenital cytomegalovirus infection therapy: case study

Cytomegalovirus infection is the most common congenital infection, causing development disorders of the fetus’ nervous system. The article describes two clinical cases of congenital cytomegalovirus infection, which highlight the crucial importance of an early administration of direct antiviral drugs (ganciclovir, valgancyclovir) for the generalized manifest forms of infection. The first clinical case study (a girl, most likely infected at the beginning of the second trimester of pregnancy) deals with the development of the classic triad of severe congenital CMV infection (small weight for gestational age, direct hyperbilirubinemia and petechial rash). Given that the intrauterine developmental anomalies specific for CMV were detected in the fetus on the 32nd week of pregnancy during her mother’s comprehensive test examination, the treatment of the infant girl with ganciclovir could have started immediately after her birth. The second clinical case study describes a congenital generalized cytomegalovirus infection in a child with malformations of internal organs and the central nervous system. The described two clinical cases of congenital cytomegalovirus infection highlight the crucial importance of ganciclovir and point to the fact that the isolated use of hyperimmune immunoglobulin does not stop the progression of the disease. The chance of a favorable outcome of the disease is much higher if the clinical diagnosis is established as early as possible after the birth of the child and etiotropic therapy is fully administered.

Artículo traducido] Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida

BackgroundHereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. ObjectiveTo evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. MethodsA comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2–4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2–3; mean 2.61) vs 2 (IQR 2–3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. ConclusionsDWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Clinical analysis of the nose on Down syndrome patients in the Minangkabau tribe

Background: Down's syndrome (DS) is a congenital disorder due to prenatal trisomy 21 which causes malformations of organs and body shape, including the nose. The variables measured are the points that determine the aesthetics of the nose. Purpose: This study aimed to describe primary data thus obtained from nose anthropometry of Down syndrome in the Minangkabau tribe can be used as a reference in nose reconstruction in patients with Down syndrome to restore physiological function and add aesthetic value. Methods: This research is a descriptive type study with a cross-sectional method using primary data as subjects. The sample of this study were people with Down syndrome who have Minangkabau ethnicity, totaling 22 samples with an age range of 13-25 years from special schools in Padang city. The study was conducted by observation and anthropometry of the nose using graphical images computerized by software called rhinobase software. Results: The results of this study showed that the nose width is 15.25 mm ± 2.07, the ala nasi width is 41.41 mm ± 3.47, the nasofrontal angle was 133.59° ± 5.89, the nasolabial angle was 109.24° ± 13.60 , the nose length is 32.16 mm ± 3.24. Conclusion: From this study, various results were found on the size of the aesthetic points of the nose of Down syndrome patients in the Minangkabau ethnic group when compared to DS patients in different race, ethnic, or non DS patients.

Prime-Editing of human ACTB in induced pluripotent stem cells to model human ACTB Loss-of-Function diseases and compensatory mechanisms

Beta-actin (ACTB) heterozygous loss-of-function mutations are associated with pleiotropic developmental disorders entailing intellectual disability and frequent organ malformations in affected individuals. We generated two CRISPR/Cas9 prime-edited human induced pluripotent stem cell (iPSC) lines, IUFi004-A-1 and IUFi004-A-2, carrying a heterozygous missense mutation in exon 4 of ACTB. Mutant iPSCs exhibited normal cell morphology and genomic integrity, maintained expression of pluripotency markers, and differentiated into the three primary germ layers. The mutants offer a valuable platform for examining the molecular and functional consequences of ACTB haploinsufficiency, developing effective treatments, and exploring mechanisms underlying phenotypic variability and genetic compensation observed in monogenic diseases.

Hereditary Hemorrhagic Telangiectasia with Recurrent Epistaxis, Telangiectasia, Hepatic Arteriovenous Malformation, and a Poorly Developed Middle Cerebral Artery in a Patient with a Novel Mutation in the ACVRL1 Gene.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by intractable epistaxis, mucocutaneous telangiectasias, and arteriovenous malformations (AVMs) in multiple organs, including the lungs, liver, gastrointestinal tract, brain, and spinal cord. We herein report a 50-year-old Japanese man with HHT who experienced recurrent epistaxis, telangiectasia in the cornea, apex of the tongue and fingers; hepatic AVM; and a poorly developed main arterial trunk in the right middle cerebral artery. A genetic analysis revealed a novel heterozygous mutation in the activin A receptor-like type 1 gene, with a frameshift mutation in NM_000020.3:c.826_836del (p.Ile276ProfsTer112).

Jujube Witches' Broom Phytoplasma Effector Zaofeng3, a Homologous Effector of SAP54, Induces Abnormal Floral Organ Development and Shoot Proliferation.

Plant-pathogenic phytoplasmas secrete specific virulence proteins into a host plant to modulate plant function for their own benefit. Identification of phytoplasmal effectors is a key step toward clarifying the pathogenic mechanisms of phytoplasma. In this study, Zaofeng3, also known as secreted jujube witches' broom phytoplasma protein 3 (SJP3), was a homologous effector of SAP54 and induced a variety of abnormal phenotypes, such as phyllody, malformed floral organs, witches' broom, and dwarfism in Arabidopsis thaliana. Zaofeng3 can also induce small leaves, dwarfism, and witches' broom in Ziziphus jujuba. Further experiments showed that the three complete α-helix domains predicted in Zaofeng3 were essential for induction of disease symptoms in jujube. Yeast two-hybrid library screening showed that Zaofeng3 mainly interacts with proteins involved in flower morphogenesis and shoot proliferation. Bimolecular fluorescence complementation assays confirmed that Zaofeng3 interacted with these proteins in the whole cell. Overexpression of zaofeng3 in jujube shoot significantly altered the expression patterns of ZjMADS19, ZjMADS47, ZjMADS48, ZjMADS77, and ZjTCP7, suggesting that overexpressing zaofeng3 might induce floral organ malformation and witches' broom by altering the expression of the transcriptional factors involved in jujube morphogenesis.

Individual Treatment Trial of PIGV-Associated Mabry Syndrome with D-Mannose in a Young Child

We describe the first individual treatment trial with D-mannose in a young girl with PIGV-CDG. PIGV-CDG belongs to the GPI anchor deficiencies leading to intellectual disability, dysmorphic features, epilepsy, and, less frequently, organ malformations. A hallmark of the GPI anchor deficiencies is the elevated serum alkaline phosphatase (AP). Our patient carried the germline homozygous PIGV variant c.1022C&gt;A, p. (Ala341Glu), the most commonly reported pathogenic variant leading to PIGV-CDG so far. We aimed to improve the impaired enzymatic function of PIGV through elevated substrate levels by giving D-mannose orally. We monitored the clinical status, developmental progress as well as serum AP levels. Our patient experienced no side effects. Standardized developmental testing showed better developmental progress during the 21-month treatment period with D-mannose than in the 12 months following the discontinuation of treatment. The D-Mannose treatment might have had a positive effect on the development of our patient with PIGV-CDG.

CLINICAL, ULTRASOUND AND CYTOGENETIC CHARACTERISTICS OF FETUSES WITH INCREASED NUCHAL TRANSLUCENCY THICKNESS IN THE FIRST TRIMESTER OF PREGNANCY

Background: Improving programs for early prenatal detection of congenital malformations remains a relevant scientific and practical problem. The prevalence of congenital anomalies in Ukraine is 23.7:1000 among live-born babies, and there is no significant decrease in it. The aim of this study was to compare clinical, ultrasound and cytogenetic data in swollen fetuses with increased nuchal translucency (NT) thicknesses from the group of pregnant women in the first trimester at high genetic risk to optimize the algorithm of prenatal diagnostics.&#x0D; Materials and Methods: Clinical examinations, ultrasound diagnostics, invasive methods of prenatal diagnostics (chorion biopsy, amniocentesis), genetic testing techniques, such as karyotyping and FISH, genetic counseling and statistical analysis were carried out. The results of complex examinations of 127 fetuses with an increased NT thickness from the group of pregnant women were analyzed. Fetuses were divided into two groups with an NT thickness of 2.5–3.5 mm (group 1) (38 cases) and with an NT above 3.5 mm (group 2)(89 cases).&#x0D; Results: Among pregnancies with fetuses with an increased NT thickness, there were 65.4% cases of adverse outcomes with chromosomal pathology (69.9%), congenital malformations of non-chromosomal etiology (25.3%) and pregnancy loss (4.8%). The frequency of chromosomal abnormalities in fetuses of group 1 was 55.3% and 41.6% in group 2. Congenital malformations of various systems and organs in fetuses, the most frequent of which were cardiac defects, were diagnosed. The ratio of congenital heart defects in the fetuses of groups 1 and 2 was 23.7% and 43.8%, respectively (p=0.03; OR=0.40).&#x0D; Conclusion: There is no significant difference between the frequency of chromosomal abnormalities in the fetuses of group 1 compared to group 2, which indicates a high informative value of an increased NT thickness, including the thickness of 2.5–3.5 mm in fetuses in the first trimester as a marker of chromosomal pathology. A significantly higher incidence of congenital malformations of non-chromosomal etiology was found in fetuses with venous duct pathology and NT thickness over 3.5 mm compared to fetuses with the same pathology and NT thickness of 2.5–3.5 mm. Proposed changes to the management algorithm for pregnant women with swollen fetuses include mandatory congenital heart defects screening in the first trimester.

In ovo o,p'-DDT exposure induces malformation of reproductive organs and alters the expression of genes controlling sexual differentiation in Japanese quail embryo.

In ovo exposure to o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p'-DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p'-DDT-containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 μg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti-Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p'-DDT dose-dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p'-DDT dose-dependently decreased estrogen receptor (ER) α, ERβ, and AMHR2 mRNA expression. o,p'-DDT dose-dependently induced left-biased asymmetry of testis size, and ovary-like tissue was found in the left testis after exposure to 8,000 μg per egg o,p'-DDT, although asymmetric gene expression did not occur. o,p'-DDT did not affect ovarian tissue but did decrease 17α-hydroxylase/C17-20 lyase mRNA expression and dose-dependently increased ERβ mRNA expression. o,p'-DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p'-DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals.

Physiological effects of polycyclic aromatic hydrocarbons (PAH) in fish organism

The pollution of world ocean is a serious threat to the biodiversity of flora and fauna. One of the most important sources of pollution are oil and oil products – every year more than 1 million tons of oil is spilled into the sea as a result of accidents during oil production or transportation. The teratogenic and carcinogenic effects of such oil components as benzopyrene is well known since the middle of the last century. However, after a large oil spill from “Exxon Valdez” tanker in 1989 it became clear that oil and its components have strong toxic effects in fish organism – and to a large extent these effects are caused by di- and tricyclic aromatic hydrocarbons, in particular phenanthrene. Field research have demonstrated that fish embryo and larvae are the most prone to the effects of oil – and the largest oil spills endanger the populations of important commercial fish species that spawn in this area. This review considers the influence of polycyclic aromatic hydrocarbons (PAH) on the physiology of various organ systems in fish. Particular attention is paid to the cardiotoxic effects of PAH which were recently discovered and which are potentially not only the main cause of animals’ death upon the spill of PAH into water, but also underlie the malformation of other organs.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation

BackgroundHereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. ObjectiveTo evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. MethodsA comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. Results111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2–4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2–3; mean 2.61) vs 2 (IQR 2–3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. ConclusionsDWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Endovideosurgical interventions in the bladder diverticulum in children

Introduction. Among congenital and acquired malformations in the urinary system organs, one of the topical issues is the choice of management modalities in bladder diverticulum. Modern equipment and development of minimally invasive techniques have expanded the variability of curative approaches, which is especially important for children with comorbidities.Purpose. To optimize surgical treatment of children with bladder diverticulum using minimally invasive surgical interventions, to reduce the rate of intraoperative and postoperative complications as well as to improve endovideosurgical access for the successful implementation of reconstructive interventions based on the authors' analysis of their own material on treating children with bladder diverticula.Material and methods. Five patients of different age having a bladder diverticulum with various anatomical features and with comorbidities were treated at the surgical department of St. Luka Clinical Research Specialized Center for Children (Moscow, Russia) in 2021–2022. The researchers could find the principle for selecting a proper surgical modality after they had assessed positive and negative aspects of each type of surgical access.Results. While choosing the type of surgical access in the discussed patients, the authors took into account anatomical features, concomitant pathologies, findings of instrumental diagnostics. As a result, all patients had good outcomes. The authors demonstrated a successful application of endovideosurgical techniques in the management of patients with congenital bladder diverticula after they had analyzed their own clinical material. They also described effective techniques for reconstructing ureterovesical anastomosis area with consideration of its place in relation to the diverticulum.Conclusion. The pneumovesicoscopic access for congenital bladder diverticulum removal is the most rational one, as it allows to accurately restore the relationship of anatomical structures.

SAT436 Endocrine Disruptor Of Organochlorine Pesticides Levels In Saudi Arabian Produce

Abstract Disclosure: M.S. Alokail: None. N.M. Al-Daghri: None. A.M. Alnaami: None. S. Sabico: None. S.D. Hussain: None. O.E. Amer: None. S.H. Abd-Alrahman: None. Food monitoring (FM) is a system used to evaluate and monitor hazardous contaminants, including pollutants such as organochlorine pesticides (OCPs). Long term exposure to organochlorine pesticides (OCPs) can lead to a variety of endocrine and reproductive disruptors including gonadal changes, changes in reproductive behavior, reduced sperm quality, an increase in organ malformations, testicular failure, fetal defects, thyroid dysfunction, and lactation. The present study aimed to determine and quantify OCPs in different local produce collected from different regions in Saudi Arabia. A total of 179 local produce samples were obtained in four regions in Saudi Arabia: Riyadh (N=55), Qassim (N=61), Eastern province (N=38) and Western region (N=25). Solid phase extraction method (QuEChERS) was used to detect OCP residues in samples and levels were quantified using gas chromatograph-electron capture detector (GC-ECD). The results have shown that a total of 11 OCPs were detected overall (9 OCPs in Qassim, Eastern province and Riyadh; 8 in Western region). Levels of alpha BHC was highest in Riyadh; 6 OCPs were highest in Qassim (Beta-BHC, Delta BCH, Dieldrin, Gamma-BHC, heptachlorepoxide and heptachlor); 4 OCPs were highest in the Eastern province (DDD, DDE, endosulfan and endrin), with endrin and endosulfan having the highest levels among all OCPs assessed. A total of 6 OCPs were found in all regions at varying concentrations (Beta-BHC, DDE, Delta-BCH, Dieldrin, endosulfan and heptachlor. Worthy to note is that heptachlorepoxide was found only in Qassim. In conclusion, the endocrine disruptor pesticides such as OCP residues require further investigation for a possible etiologic role in some hormone related cancers such as breast cancer. Presentation: Saturday, June 17, 2023

Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.

Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.

HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.

Pulmonary hypertension— a novel phenotypic hypothesis of Kabuki syndrome: a case report and literature review

BackgroundPediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations.Case presentationA 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory.ConclusionsKS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.

Psychoneurological Disorders in Children with Congenital Aniridia and &lt;i&gt;PAX6&lt;/i&gt;-Associated Syndromes

Congenital aniridia manifests with total or partial absence of the iris. The association of the disease with the PAX6 gene has been proven. Changes in the PAX6 structure lead to intrauterine pathology, visual organ malformation, malformation of master regulator proteins of organogenesis affecting various cells’ differentiation (central nervous system cells included). Such disorders result into the development of PAX6-associated syndromes with various brain malformations, neurological disorders, and systemic pathology (thyroid pathology, Wilms tumor, glucose intolerance). Isolated congenital aniridia is also accompanied by psychoneurological disorders. It can be associated with brain structures’ disorders during embryogenesis and with impact of external stress factors on the child (frequent medical checkup, surgical treatments). The psychoneurological disorders’ pathogenesis as well as congenital aniridia’s genetic mechanisms remain unclear. Thus, it is crucial to review new relevant data within the context of previously obtained information to gather full picture of the clinical signs of the disease and to improve the management of children with congenital aniridia.