Hepatobiliary Ultrasonographic Abnormalities in Adult Patients with Sickle Cell Anaemia in Steady State in Ile-Ife, Nigeria.

BACKGROUND: Sickle cell anaemia (SCA) is associated with structural manifestations in the hepatobiliary axis. This study aimed to investigate the hepatobiliary ultrasonographic abnormalities in adult patients with sickle cell anaemia in steady state attending the Haematology clinic of a federal tertiary health institution in Ile-Ife, Nigeria. MATERIAL/METHODS: Basic demographic data as well as right upper abdominal quadrant ultrasonography of 50 consecutive sickle cell anaemia patients were compared with those of 50 age- and sex-matched subjects with HbAA as controls. RESULTS: Each of the study groups (patients and controls) comprised of 21 (42%) males and 29 (58%) females. The age range of the patients was 18-45 years with a mean (±SD) of 27.6±7.607 years, while that of the controls was 21-43 years with a mean (±SD) of 28.0±5.079 years (p=0.746). Amongst the patients, 32 (64%) had hepatomegaly, 15 (30%) cholelithiasis and 3 (6%) biliary sludge. Fourteen (28%) of the patients had normal hepatobiliary ultrasound findings. In the control group, one (2%) person had cholelithiasis, one (2%) biliary sludge, one (2%) fatty liver and none hepatomegaly. Forty-seven (94%) of the controls had normal hepatobiliary ultrasound findings. There was a statistically significant difference in the prevalence of hepatomegaly and cholelithiasis between the patients and controls (p value <0.001 for both comparisons). CONCLUSIONS: In this study, hepatomegaly, cholelithiasis and biliary sludge were the most common hepatobiliary ultrasound findings in patients with sickle cell anaemia. Ultrasonography is a useful tool for assessing hepatobiliary abnormalities in patients with sickle cell anaemia.

Anomalous Origin of All Coronary Arteries from Right Sinus of Valsalva.

Anomalous coronary arteries are rare and often incidental findings. Most variants are benign. We present the case of a 75-year-old man with exertional dyspnea in whom the left anterior descending coronary artery arose from the right sinus of Valsalva, and the left circumflex coronary artery originated from the distal right coronary artery and supplied the obtuse marginal branch. No arteries originated from the left sinus of Valsalva. The patient was prescribed optimal medical therapy for atherosclerotic stenosis in his ramus intermedius. His symptoms were stable 3 years later.

Effectiveness of Bidirectional Glenn Shunt Placement for Palliation in Complex Congenitally Corrected Transposed Great Arteries.

Surgery for complex congenitally corrected transposed great arteries is one of the greatest challenges in cardiovascular surgery. We report our experience with bidirectional Glenn shunt placement as a palliative procedure for complex congenitally corrected transposition. We retrospectively identified 50 consecutive patients who had been diagnosed with congenitally corrected transposition accompanied by left ventricular outflow tract obstruction and ventricular septal defect and who had then undergone palliative bidirectional Glenn shunt placement at our institution from January 2005 through December 2014. Patients were divided into 3 groups according to subsequent surgeries: Fontan completion (total cavopulmonary connection, 13 patients) (group 1), anatomic repair (hemi-Mustard and Rastelli procedures without Glenn takedown, 11 patients) (group 2), and prolonged palliation (no further surgery, 26 patients) (group 3). After shunt placement, no patient died or had ventricular dysfunction. Overall, mean oxygen saturation increased significantly from 79.5% ± 13.5% preoperatively to 94.1% ± 7.3% (P <0.001). The median time from shunt placement to Fontan completion and anatomic repair, respectively, was 2.1 years (range, 1.6-5.2 yr) and 1.1 years (range, 0.6-2.4 yr). Only 2 late deaths occurred, both in group 1. In group 3, time from shunt placement to latest follow-up was 4.5 years (range, 2.3-8 yr). At latest follow-up, mean oxygen saturation was 91.6% ± 10.3%, and no patients had impaired ventricular function. Bidirectional Glenn shunt placement as an optional palliative procedure for complex congenitally corrected transposition has favorable outcomes. Later, patients can feasibly be treated by Fontan completion or anatomic repair. Use of a bidirectional Glenn shunt for open-ended palliation is also acceptable.

Anomalous Origin of the Right Coronary Artery from the Pulmonary Artery in a Neonate with Turner Syndrome and Aortic Arch Hypoplasia.

Anomalous origin of the right coronary artery from the pulmonary artery, a rare congenital cardiac defect, is typically not diagnosed during infancy. On the other hand, Turner syndrome is usually diagnosed early, and it is classically associated with bicuspid aortic valve and aortic coarctation. Individuals with Turner syndrome are also at increased risk for coronary artery anomalies. We present a case of anomalous right coronary artery from the pulmonary artery in a week-old neonate who also had Turner syndrome, patent ductus arteriosus, transverse aortic arch hypoplasia, and impaired ventricular function. Prostaglandin therapy through the ductus increased the patient's myocardial perfusion. Four months after corrective surgery, she was doing well. We discuss the reperfusion phenomenon in our patient's case, as well as other considerations in this combination of congenital defects.

Ventricular septal defect closure in a patient with VACTERL syndrome: anticipating sequelae in a rare genetic disorder.

Noncardiac components of genetic disorders can complicate the operative and postoperative courses of pediatric cardiac surgery patients. Prolonged hospital stay, increased treatment cost, morbidity, and death are more likely in this subgroup of patients. Ventricular septal defect, which is a component of various genetic disorders, has a 22.3% incidence in VACTERL syndrome--a rare, nonrandom pattern of birth defects. Herein, we discuss the impact of ventricular septal defect closure in a 4-month-old girl who was diagnosed after birth with VACTERL syndrome.

Management of right-sided fetal congenital diaphragmatic hernia with hepatopulmonary fusion: a report of three cases and literature review / 中华围产医学杂志

Objective:To investigate the clinical features and management of right-sided congenital diaphragmatic hernia (RCDH) with hepatopulmonary fusion (HPF).Methods:This retrospective study analyzed the clinical characteristics of three cases of RCDH complicated by HPF that were treated in Guangzhou Women and Children's Medical Center from June to December 2022. Diaphragm defects in the three cases were classified according to the international standard of diaphragm defect classification. Besides, an extensive search of publications was performed including domestic and foreign databases, including CNKI, Wanfang Database, Yiigle, VIP Chinese journals, PubMed, Embase and UpToDate databases from January 1997 to April 2023 using terms including "congenital diaphragmatic hernia" and "hepatopulmonary fusion". Clinical features and prognosis of RCDH complicated by HPF were summarized.Results:(1) Cases in the present study: RCDH was found in case 1 and case 2 during routine prenatal ultrasound examination; antenatal fetal MRI showed partial displacement of the hepatocele into the right hemithorax, right lung hypoplasia, a normal-sized left lung and without left shift of the mediastinum in both cases. Postnatal chest radiographs of case 1 and case 3 showed dense shadow in the left lung and mediastinum shifted to the right. Case 2 had a D-type defect and a slight shift of the mediastinum to the left was observed on the postnatal chest radiograph. Preoperative imaging findings indicated highly suspected HPF in the three cases. Case 1 and case 2 had complete separation of liver and lung and underwent diaphragmatic herniorrhaphy with patch. Partial lung resection was performed in case 2. Both case 1 and case 2 survived (length of hospital stay was 22 d and 23 d, respectively). Case 3 did not undergo hepatopulmonary separation or herniorrhaphy after exploratory operation and died of persistent pulmonary hypertension. (2) Literature review: Only 40 cases of CDH with HPF were retrieved from PubMed. Among the 43 cases including the above three cases, 27 (62.8%) had a right shift or no deviation of the mediastinum before surgery and nine (20.9%) had a left shift of the mediastinum, while the condition of seven patients (16.3%) were not described. There were 26 patients undergoing complete separation of liver and lung and 19 (73.1%) of them survived. Thirteen patients underwent partial separation of liver and lung and six of them survived. Four patients died without receiving separation.Conclusions:HPF should be considered in patients with RCDH, especially in cases with no left shift in the mediastinum in the imaging. Preoperative evaluation for surgery in such cases needs to be managed as if it were a major operation that may require hepatectomy or partial pneumonectomy.

Prenatal diagnosis of fetal diencephalic-mesencephalic junction dysplasia: a case report / 中华围产医学杂志

We report a case of fetal diencephalic-mesencephalic junction dysplasia (DMJD) diagnosed prenatally. Prenatal ultrasound at 24 gestational weeks showed that the fetus was small, about the size at 22 weeks' gestation, with short biparietal diameter and enhanced echo at the anterior border of thalamus. Fetal MRI showed short T2 signal shadow in the left choroid plexus, and hemorrhage and midbrain dysplasia were suspected. A pathogenic homozygous mutation variant in protocadherins 12 gene (c.1558C>T) was found in this fetus by whole exome sequencing and both parents carried the same heterozygous variation revealed by Sanger sequencing. All of the above information lead to the diagnosis of fetal DMJD, and the pregnancy was terminated after genetic counseling.

Townes-Brocks syndrome caused by de novo mutation in spalt-like transcription factor 1 gene: a case report and literature review / 中华围产医学杂志

Objective:To summarize the clinical features and gene variations in children with Townes-Brocks syndrome (TBS).Methods:The clinical data of a female infant diagnosed with TBS caused by human spalt-like transcription factor 1 ( SALL1) gene mutation in Gansu Maternal and Child Health Hospital in May 2022 were analyzed retrospectively. Relevant articles up to July 2022 were retrieved from several databases including CNKI, VIP, Wanfang, Chinese Medical Journal Network and PubMed with the terms of " SALL1 gene" and "Townes-Brocks syndrome". Patients diagnosed with TBS caused by SALL1 gene mutation were retrieved and the clinical phenotype-genotype correlations in patients with TBS caused by frameshift mutation in SALL1 gene were analyzed and summarized. Descriptive statistical analysis was applied. Results:(1) Clinical data: The index patient was a 40-day-old girl exhibiting major clinical manifestations of polycystic kidney dysplasia, congenital external ear deformity, preaxial polydactyly and recto-perineal fistula. Whole exome sequencing and Sanger sequencing revealed a heterozygous variation of c.420delC (p.S141fs*42) in the SALL1 gene, while the same gene was found to be wild type in her parents and sister. The variant was predicted to be pathogenic (PVS1+PS2+PM2). (2) Literature review retrieved 161 cases of TBS, of which 71 were attributable to a frameshift mutation in SALL1 gene. Clinical phenotypes of the 71 cases and the index case were summarized. TBS was mainly characterized by external ear, hand and anal deformities, sometimes accompanied by hearing loss, abnormal kidney development and foot deformity. A small number of affected cases presented with rare clinical phenotypes such as abnormal eyes, hypothyroidism and abnormal development. At present, the human gene mutation database records 110 variations in the SALL1 gene, with a majority located in exon 2. The most common mutation type was frameshift variation, accounting for 52%, followed by missense variation and nonsense variation. Conclusion:TBS should be considered in children with ear, hand and anal malformations, accompanied by renal dysfunction and hearing loss, and genetic testing is recommended for timely diagnosis.

Prenatal sonographic diagnosis of urorectal septum malformation sequence in one of twins: a case report / 中华围产医学杂志

Urorectal septum malformation sequence (URSMS) is a rare congenital complex malformation characterized by severe abnormalities in the urinary, reproductive and digestive systems. It is difficult to diagnose URSMS by prenatal ultrasound due to its complex and variable manifestations. This paper reported a twin with partial URSMS. Prenatal ultrasound findings included pelvic "trilobe" cystic masses, sacrococcygeal hemivertebral malformations, imperforate anus, and transient ascites. Postnatal examination confirmed the diagnosis of URSMS, as the baby girl was born with anal atresia. Her colon, urethra, and vagina converged and formed a common tract with a single perineal opening. The baby died after her parents' refusal to surgical treatment.

Prenatal diagnosis of fetal ZTTK syndrome: a case report / 中华围产医学杂志

This article reported the prenatal diagnosis of a fetus with ZTTK syndrome. A pregnant woman underwent preimplantation genetic diagnosis because her partner carried a balanced chromosomal translocation. Chromosomal karyotype analysis and copy number variation sequencing (CNV-seq) performed on amniocytes collected at 18 + weeks of gestation revealed no abnormalities. Ultrasonography performed at 23 +5 and 26 +3 weeks of gestation revealed severe fetal growth restriction, cerebellar dysplasia, poorly visualized sacrum and coccyx, and spina bifida. MRI of the fetal brain showed that the bilateral cerebellar hemispheres of the fetus were small and the cisterna magna was large at 23 +6 weeks of gestation. Whole exome sequencing in the pedigree identified a heterozygous variant c.2092delG (p.Glu698fs*4) in the exon 3 of the fetal SON gene, which was not inherited from the parents and proved to be a de novo mutation. Mutations in the locus are pathogenic, causing ZTTK syndrome. After genetic counseling, the pregnant woman and her family chose to terminate the pregnancy.

Asociación entre las variantes anatómicas del complejo osteomeatal y patología inflamatoria sinusal: estudio de casos y controles / Association between anatomical variants of the osteomeatal complex and inflammatory sinus pathology: case-control study

Introducción: las variantes anatómicas nasosinusales pueden ser una causa frecuente de infecciones crónicas, y resulta importante identificarlas en la práctica diaria. Objetivo: determinar la asociación entre las variantes anatómicas del complejo osteomeatal (COM) y el desarrollo de patologías inflamatorias nasosinusales. Materiales y métodos: estudio de casos y controles, muestra de 226 pacientes identificando las variantes anatómicas del COM en la tomografía computada (TAC) de senos paranasales (SPN) y su correlación clínica. Resultados: el 51,9 % presentaron hallazgos imagenológicos indicativos de patología inflamatoria nasosinusal y el 19,8 % reportaron sintomatología sugestiva de sinusitis en la historia clínica. Los SPN más afectados fueron: maxilares (46,9 %) y etmoidales (23 %). Las variantes anatómicas más frecuentes fueron las celdillas de Agger Nasi (50,2 %) y la desviación septal (46,2 %). Se encontró como variable estadísticamente significativa la inserción lateral de la apófisis unciforme (p = 0,015) más frecuente del lado izquierdo (p = 0.018, odds ratio [OR] = 4,078, intervalo de confianza [IC] 95 % = 1,3-12,6). Discusión: Se confirmó la incidencia de las variantes anatómicas más frecuentes en la literatura, sin embargo, no se correlacionan con los hallazgos clínicos para la serie de pacientes estudiada en comparación con otros estudios. Existe una alta relación entre la inserción lateral de apófisis unciforme y hallazgos de rinosinusitis escasamente documentados en la literatura médica. Conclusión: se requieren más estudios sobre modelos predictivos en muestras poblacionales mayores y protocolos de lectura TAC enfocados sobre diferentes variantes anatómicas de la apófisis unciforme.

Introduction: Sinonasal anatomical variants can be a frequent cause of chronic in- fections, so it is important to identify them in daily practice. Objective: To determine the association between the anatomical variants of the osteomeatal complex (OCM) and the development of sinonasal inflammatory pathologies. Materials and methods: Case-control study, a sample of 226 patients is analyzed identifying the anatomical variants of OCM in computed tomography of the paranasal sinuses and their clinical correlation. Results: 51.9% presented imaging findings indicative of sinonasal in- flammatory disease, 19.8% reported symptoms suggestive of sinusitis in the clinical history. The most affected paranasal sinuses were: maxillary (46.9%) and ethmoid (23%). The most frequent anatomical variants were Agger Nasi cells (50.2%) and septal deviation (46.2%). The lateral insertion of the uncinate process (p=0.015) was a statistically significant variable, more frequent on the left side (p=0.018, odds ratio [OR]=4.078, 95% confidence interval [CI]=1.3-12.6). Discussion: The incidence of the most frequent anatomical variants in the literature was confirmed, however not correlated with the clinical findings for the series of patients studied in comparison with other studies. There is a high relationship between the lateral insertion of the uncinate process and rhinosinusitis findings that are scarcely documented in the medical literature. Conclusion: More studies are required on predictive models in larger population samples and tomographic reading protocols focused on different anatomical variants of the uncinate process

Aortic translocation with autologous tissue.

Aortic translocation, although technically demanding, could be an excellent surgical option for d-transposition of the great vessels and left ventricular outflow tract obstruction. We report a modification of the aortic translocation technique that uses autologous tissue. The aortic root is mobilized from the right ventricle with an extension of infundibular free-wall muscle for use in closure of the ventricular septal defect, which is similar to the technique for harvesting pulmonary autograft in the Ross-Konno procedure. Our modification may offer an even better surgical outcome for aortic translocation.

Prenatal ultrasonographic characteristics and prognosis of fetal umbilical-portal-systemic venous shunt: analysis of 14 cases / 中华围产医学杂志

Objective:To summarize the prenatal ultrasonographic features and prognosis of fetal umbilical-portal-systemic venous shunt (UPSVS).Methods:This retrospective study retrieved the records of 14 fetuses with UPSVS from Chongqing Health Center for Women and Children from January 2018 to September 2020, to describe their ultrasonographic features, concomitant malformations, chromosomal examination results, and follow-up.Results:All the 14 cases were classified into three types: Type Ⅰ ( n=2), the umbilical vein directly connected to the systemic venous detouring around the liver; Type Ⅱ ( n=2), the umbilical vein connected to the distal inferior vena cava instead of the left atrium after entering the liver through the ductus venosus; and Type Ⅲa ( n=10), those with an intrahepatic shunt, between the intrahepatic portal venous system and the hepatic vein. Of the 14 fetuses, 11 had normal chromosome test results, including four had serum screening of Down syndrome in the first trimester, four had non-invasive prenatal testing, and three had prenatal genetic diagnosis. Six cases were complicated by other system malformations. Fetal growth restriction and heart failure were found in four cases each. Four pregnancies were terminated due to other anomalies and the other 10 ended in live births with good prognosis for the fetuses. Conclusions:Special attention should be paid to the fetal umbilical- portal-venous system when there are unexplained fetal growth restriction, fetal heart failure, or abnormal blood vessels in the abdominal section of the fetus. UPSVS has typically ultrasonographic features, which can prenatally determine the shunt type and the integrity of the intrahepatic portal venous system. A full assessment of the intrauterine fetal condition and other malformations are of great value in prognostic counseling.

Repair of Intrapericardial Diaphragmatic Hernia during Aortic Surgery in a 78-Year-Old Woman.

Intrapericardial diaphragmatic hernias are reported very rarely. Those of congenital origin are most often diagnosed in neonates, and those caused by indirect blunt trauma occur chiefly in adults. The latter type can be asymptomatic; however, the results of a computed tomographic scan can yield a definitive diagnosis. Once discovered, these hernias should be corrected to avoid severe sequelae such as bowel strangulation and necrosis, peritonitis, mediastinitis, and cardiac tamponade. We report the case of a 78-year-old woman who presented for elective ascending aortic aneurysm repair. Computed tomographic angiograms incidentally revealed a large intrapericardial diaphragmatic hernia, which had probably developed years earlier, after a traffic accident. The patient underwent a median sternotomy and repair of the intrapericardial diaphragmatic hernia with use of a bovine pericardial patch, followed by ascending aortic and hemiarch repair, aortic valve repair, and aorto-right coronary artery bypass grafting. We discuss the details of these procedures and alternative treatment options. To our knowledge, this is the first report of concomitant aortic surgery and repair of a trauma-induced intrapericardial diaphragmatic hernia in an adult.

A Rare Case of Vascular Ring and Coarctation of the Aorta in Association with CHARGE Syndrome.

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring-consisting of a right aortic arch with retroesophageal brachiocephalic artery-combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution. To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case of these combined disorders occurring in CHARGE syndrome. This report describes a truly rare case and reveals the limitations of echocardiography in detecting complex aortic arch anomalies while illustrating the benefits of advanced imaging prior to surgical intervention.

Ruptured Sinus of Valsalva Aneurysm Associated with Situs Ambiguus, Isolated Levocardia, and Polysplenia.

Aneurysm of the sinus of Valsalva, a rare cardiac condition, results from dilation of an aortic sinus. Sudden aneurysm rupture can trigger rapidly progressive heart failure. We discuss the case of a 57-year-old woman with situs ambiguus, isolated levocardia, and polysplenia who presented with acute-onset heart failure. Transesophageal echocardiograms revealed an aneurysm of the right coronary sinus of Valsalva that had ruptured into the right atrial cavity. The patient underwent successful surgical repair. To our knowledge, this is the first report of a sinus of Valsalva aneurysm in a patient with this combination of congenital abnormalities. We briefly review the association between congenital heart disease, situs ambiguus, and ciliary dysfunction.

Prospective Evaluation of Kidney Disease in Joubert Syndrome.

BACKGROUND AND OBJECTIVES: Joubert syndrome is a genetically heterogeneous ciliopathy associated with >30 genes. The characteristics of kidney disease and genotype-phenotype correlations have not been evaluated in a large cohort at a single center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated 97 individuals with Joubert syndrome at the National Institutes of Health Clinical Center using abdominal ultrasonography, blood and urine chemistries, and DNA sequencing. RESULTS: Patients were ages 0.6-36 years old (mean of 9.0±7.6 years old); 41 were female. Mutations were identified in 19 genes in 92 patients; two thirds of the mutations resided in six genes: TMEM67, C5orf42, CC2D2A, CEP290, AHI1, and KIAA0586. Kidney disease was detected in 30%, most commonly in association with the following genes: CEP290 (six of six), TMEM67 (11 of 22), and AHI1 (three of six). No kidney disease was identified in patients with mutations in C5orf42 (zero of 15) or KIAA0586 (zero of six). Prenatal ultrasonography of kidneys was normal in 72% of patients with kidney disease. Specific types of kidney disease included nephronophthisis (31%), an overlap phenotype of autosomal recessive polycystic kidney disease/nephronophthisis (35%), unilateral multicystic dysplastic kidney (10%), and indeterminate-type cystic kidney disease (24%). Early-onset hypertension occurred in 24% of patients with kidney disease. Age at ESRD (n=13) ranged from 6 to 24 years old (mean of 11.3±4.8 years old). CONCLUSIONS: Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in CEP290, TMEM67, and AHI1. Patients with mutations in C5orf42 or KIAA0586 are less likely to develop kidney disease. Prenatal ultrasonography is a poor predictor of kidney involvement in Joubert syndrome. Unilateral multicystic dysplastic kidney and autosomal recessive polycystic kidney disease-like enlarged kidneys with early-onset hypertension can be part of the Joubert syndrome kidney phenotype.

Echocardiographic Classification and Surgical Approaches to Double-Outlet Right Ventricle for Great Arteries Arising Almost Exclusively from the Right Ventricle.

Selecting an appropriate surgical approach for double-outlet right ventricle (DORV), a complex congenital cardiac malformation with many anatomic variations, is difficult. Therefore, we determined the feasibility of using an echocardiographic classification system, which describes the anatomic variations in more precise terms than the current system does, to determine whether it could help direct surgical plans. Our system includes 8 DORV subtypes, categorized according to 3 factors: the relative positions of the great arteries (normal or abnormal), the relationship between the great arteries and the ventricular septal defect (committed or noncommitted), and the presence or absence of right ventricular outflow tract obstruction (RVOTO). Surgical approaches in 407 patients were based on their DORV subtype, as determined by echocardiography. We found that the optimal surgical management of patients classified as normal/committed/no RVOTO, normal/committed/RVOTO, and abnormal/committed/no RVOTO was, respectively, like that for patients with large ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries without RVOTO. Patients with abnormal/committed/RVOTO anatomy and those with abnormal/noncommitted/RVOTO anatomy underwent intraventricular repair and double-root translocation. For patients with other types of DORV, choosing the appropriate surgical approach and biventricular repair techniques was more complex. We think that our classification system accurately groups DORV patients and enables surgeons to select the best approach for each patient's cardiac anatomy.

Neonatal lateral meningocele syndrome: report of a case and literature review / 中华围产医学杂志

Objective:To investigate the clinical characteristics and pathogenic gene mutation of lateral meningocele syndrome(LMS).Methods:We retrospectively collected the clinical manifestations, laboratory examination, imaging examinations, and genetic analysis of a neonate with LMS which was diagnosed at the Department of Neonatology of the Second Affiliated Hospital of Wenzhou Medical University in May 2020. Relevant literature up to February 2021, retrieved from PubMed, OMIM, CNKI, Wanfang, and CQVIP database with the terms of "lateral meningocele syndrome", " NOTCH3", were reviewed to summarize the clinical characteristics, pathogenesis, and genetic etiology of this disease. Results:A full-term male newborn was admitted to our hospital due to feeding difficulty 7 d after birth. The clinical characteristics included hypotonia, dysphagia, hypertension, lateral spinal meningocele, craniofacial anomaly, and cryptorchidism. Abnormal spinal MRI and brainstem evoked potential were also observed. Whole exome sequencing revealed a heterozygous frameshift variation c.6667_6686del(p.Ala2223Profs*12) of NOTCH3 gene located in 19p13.12, which was not detected in the parents. Only 12 English literature were retrieved, with 17 patients from 15 pedigrees. Out of the 18 patients including the index case, 10 were genetically diagnosed as LMS. The age at diagnosis ranged from 15 d to 55 years. Regarding the clinical features, multiple lateral thoracolumbar spinal meningoceles (18/18) was the most common one, followed by retrognathia and low-set ears (16/18), eyelid ptosis and down slanting palpebral fissures (15/18), hypotonia (13/18), hypertension (11/18), developmental delay (9/18), mixed or conductive hearing loss (9/18), cardiovascular dysplasia (7/18), and cryptorchidism (7/10). A total of nine NOTCH3 gene variants were detected, all were heterozygous variants, including six frameshift and three nonsense variants. Conclusions:LMS is caused by NOTCH3 gene mutation with the clinical characteristics including multiple lateral thoracolumbar spinal meningoceles, craniofacial dysmorphisms, hypotonia, hypertension, developmental delay, difficulty in feeding, cryptorchidism, etc.

Sonographic features of Joubert syndrome in first or second trimester: report of two fetuses / 中华围产医学杂志

We report two cases of Joubert syndrome initially tentatively diagnosed by prenatal ultrasound in the first or second trimester which were thereafter confirmed by whole exome sequencing (WES). Case 1 was one of the twins who presented with increased intracranial transparency (IT) and thinner brainstem at 12 +1 gestational weeks. Ultrasound at 18 +2 weeks found multiple intracranial malformations, "molar tooth sign (MTS)" at the midbrain-hindbrain junction level in the cerebral cross section, and bilateral ventriculomegaly. Enlarged and echogenic kidneys and oligohydramnios were also detected. In case 2, ultrasound image at 17 +5 weeks of gestation indicated multiple intra-and extra cranial and extracranial malformations, MTS in the midbrain-hindbrain junction plane, bilateral ventriculomegaly, unclear cavum septum pellucidum. Extracranial anomalies were bilateral multicystic enlarged kidneys, invisible bladder, and oligohydramnios. Both fetuses underwent amniocentesis, which showed normal karyotype and no copy number variation was detected. However, variation of the TMEM67 gene (c.312+5G>A at introns 2 and c.1175C>G at exon12) was detected in both fetuses by WES, supporting the diagnosis of Joubert syndrome. Selective reduction and termination of pregnancy were performed on case 1 and case 2 at 18 +5 and 19 weeks of gestation, respectively.