A 36-Year-Old Woman With Intermittent Cyanosis.

CASE PRESENTATION: A 36-year-old woman with a medical history of opioid use disorder and frequent urinary tract infections presented to the ED from her opioid use disorder clinic, where she was found to have an oxygen saturation by pulse oximetry (Spo2) of 82% on room air. Starting 3 days before presentation, the patient's family noted worsening pale complexion and blue lips at rest. These findings of cyanosis had occurred a few times before and always resolved within a couple days without any medical intervention. She had no pulmonary symptoms outside of long-standing dyspnea with moderate exertion when at work or doing chores around the house. Her medications included methadone 160 mg daily, acetaminophen 650 mg nightly as needed, and phenazopyridine 199 mg three times daily as needed for increased urinary frequency and urethral discomfort that lasted a maximum of 4 days at a time. She confirmed she had started taking a new course of phenazopyridine 4 days before presenting to the ED. She had no dietary restrictions, had been eating her normal diet, and lived in a mobile home with her family, two dogs, and a gerbil. The patient reported using less than 10 tobacco cigarettes per day, one marijuana cigarette nightly, and no alcohol or other drugs. She worked in a warehouse stacking prepackaged bread.

The role of reticulocyte hemoglobin equivalent on the evaluation of iron deficiency and iron deficiency anemia in pediatric cyanotic heart disease: a diagnostic study in Indonesia.

BACKGROUND: In light of prolonged hypoxia, children with cyanotic heart disase (CHD) are at a high risk of developing iron deficiency iron deficiency (ID) and iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is a novel and dependable indicator for assessing iron status. However, there has been no previous study regarding cut-off value in pediatric CHD group. The purpose of this study is to assess the role of Ret-He and to establish cut-off points in the diagnosis of iron deficiency and IDA in pediatric cyanotic heart disease. METHOD: This study was conducted in two tertiary hospitals in Jakarta, Indonesia. 59 children with CHD, aged 3 months to 18 years, were enrolled consecutively. To determine iron status, hematological parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin) and biochemical parameters for iron status (serum ferritin, transferrin saturation) were analysed and compared to Ret-He levels. The receiver operating characteristic (ROC) analysis was performed for the Ret-He cut-off points for ID and IDA. Sensitivity, specificity, positive and negative predictive value were calculated for each cut-off point. RESULT: Normal iron status was identified in 27 (45.8%) subjects, ID in 8 (13.5%) subjects, and IDA 24 (40.7%) subjects. The ID cut-off value for Ret-He is 28.8 pg (sensitivity 75%, specificity 85.2%, PPV 60%, NPV 92%, and AUC 0.828) and the Ret-He cut-off point for IDA is 28.15 pg (sensitivity 75%, specificity 88.9%, PPV 85.7%, NPV 80%, and AUC 0.824). Hemoglobin should be used in conjunction with Ret-He. ID might be detected in this cohort with Ret-He 28.8 pg and hemoglobin > 16,5 g/dL. While Ret-He 28.15 pg or Ret-He 28.15-28.8 pg with hemoglobin 16.5 g/dL could be used to diagnose IDA. CONCLUSION: The reticulocyte hemolgobin equivalent could be utilised as an iron status parameter in pediatric CHD, with a cut-off value of 28.8 pg for ID and 28.15 pg for IDA.

Comparative Analysis of Modified BT Shunt and Central Shunt in Pediatric Patients.

INTRODUCTION: Cyanotic congenital heart diseases constitute 40-45% of all congenital heart diseases. In patients who are not suitable for primary repair, modified BT (MBT) shunt and central shunt (CS) procedures are still frequently used. METHODS: This study included 62 pediatric patients who underwent MBT shunt or CS via median sternotomy. Patients' demographic, echocardiographic, operative, and postoperative data were collected retrospectively. The patients were classified as single ventricle and bi-ventricle according to their cardiac anatomy, and the presence of prematurity and heterotaxy was noted. Procedure details of the patients who underwent endovascular intervention prior to the surgery were investigated, and operation data were accessed from the surgery notes. Data regarding postoperative follow-ups were obtained and comparatively analyzed. RESULTS: Of the total 62 patients, 32 (51.6%) were newborns and 16 (25.8%) had a body weight < 3 kg. MBT shunt was applied to 48 patients (77.4%), while CS was applied to 14 patients (22.6%). There was no significant difference between the two surgical procedures in terms of requirement for urgent shunt or cardiopulmonary bypass, additional simultaneous surgical intervention, need for high postoperative inotropes, and in-hospital mortality (P>0.05). The rate of congestive heart failure in patients with in-hospital mortality was determined as 66.7% and it was significantly higher than in patients without heart failure (P<0.001). CONCLUSION: MBT shunt and CS are still frequently used in cyanotic patients. The use of small-diameter shunts, particularly when centrally located, can prevent the onset of congestive heart failure and lower mortality.

Cyanotic Nephropathy in an Adult Patient with Eisenmenger Syndrome: A Case Report and Literature Review.

INTRODUCTION: Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES. CASE PRESENTATION: A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength. CONCLUSION: Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.

Perioperative care of neonates with critical pulmonary stenosis: Case report.

RATIONALE: Summarizing the perioperative nursing experience in the successful treatment of 4 neonates with critical pulmonary stenosis (CPS). PATIENT CONCERNS: Of the 4 patients, 3 had postnatal shortness of breath and varying degrees of cyanosis, aggravated by crying and noise, and 1 had no obvious shortness of breath and cyanosis. The preoperative auscultation of the precordial region could be heard 3-4/6 systolic murmur; echocardiography was diagnosed as CPS, combined with patent ductus arteriosus, right ventricular dysplasia, and severe tricuspid regurgitation. Four children were treated with prostaglandin 5 ng/(kg-min) to maintain a certain degree of pulmonary blood flow to improve hypoxemia, effectively preventing ductus arteriosus from closure, and the infusion was discontinued 2 hours prior to the operation. Three of the children required ventilator-assisted respiration to relieve severe hypoxia and correct acidosis before surgery. DIAGNOSIS: Neonatal CPS was diagnosed. INTERVENTIONS: Four neonates with rapidly developing conditions were admitted to the hospital, a multidisciplinary in-hospital consultation was organized immediately, and a multidisciplinary collaborative team was set up, consisting of medical doctors and nurses from the medical department, the neonatal intensive care unit, cardiovascular medicine, cardiac ultrasound room, anesthesiology department, and radiology and interventional medicine department. The multidisciplinary team evaluated the treatment modality of the children and finally decided to perform percutaneous balloon pulmonary valvuloplasty. The surgical team included specialists from the Department of Cardiovascular Medicine, Department of Interventional Radiology, Cardiac Ultrasound Unit, and Department of Anesthesiology. OUTCOMES: All 4 neonates were successfully operated and discharged from the hospital. Multidisciplinary follow-up interventions were carried out 1 year after discharge, and the children were in good condition. LESSONS: The specialty nursing-led multidisciplinary collaboration model significantly improves the professional competence of nurses from various specialties, promotes the integration and development of multispecialty disciplines, and provides better quality services for children, which is the key to improving the success rate of percutaneous balloon pulmonary valvuloplasty in neonates.

[Clinical features of peripheral neuropathy with livedo reticularis: an analysis of seven cases].

The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.

Neuromental health aspects in adults with CHD after cardiopulmonary bypass intervention during childhood.

OBJECTIVE: It is often assumed, that adult patients with CHD (ACHD) have impairments regarding their cognitive function (CF) and health-related quality of life. In particular, it seems reasonable to assume that cyanosis may have a potential impact on CF as well as surgical or drug treatment into adulthood. This study assesses neuromental health aspects such as CF and health-related quality of life in ACHD patients. METHODS: Seventy-eight ACHD patients (female n = 39 (50%); 34.1 ± 12.9 years; cyanotic CHD n = 49 (62.8%) with a cyanosis duration of 159.8 ± 196.2 month) who underwent open heart surgery as first intervention were asked to participate during routinely follow-up in 2018. Wechsler Intelligence Scale IV was used for CF and the Short Form 36 Health Survey to assess health-related quality of life. RESULTS: Intelligence quotient measures showed significant differences comparing never cyanotic and with a cyanotic phase in verbal comprehension (p = 0.013). There was no association of CF with cyanosis duration, number of surgery or catheter, CHD severity, and time of first surgery. The group of early surgery showed significantly better results in physical function (p = 0.040) of health-related quality of life, and in comparison with their assigned reference, both groups showed significantly reduced results in all domains except in bodily pain and mental health. Full-Scale intelligence quotient correlates with physical function of health-related quality of life. CONCLUSIONS: The results show normal CF in ACHD. Health-related quality of life was weak in comparison with the reference. There is a need to improve the well-being of our ACHD with structured programmes, including physical activity programmes. This growing ACHD population should be focused in order of their needs, medical ones on one hand and on the other hand psychosocial matters.

Pulmonary reperfusion injury in post-palliative intervention of oligaemic cyanotic CHD: a new catastrophic consequence or just revisiting the same old story?

Pulmonary reperfusion injury is a well-recognised clinical entity in the setting pulmonary artery angioplasty for pulmonary artery stenosis or chronic thromboembolic disease, but not much is known about this complication in post-palliative intervention of oligaemic cyanotic CHD. The pathophysiology of pulmonary reperfusion injury in this population consists of both ischaemic and reperfusion injury, mainly resulting in oxidative stress from reactive oxygen species generation, followed by endothelial dysfunction, and cytokine storm that may induce multiple organ dysfunction. Other mechanisms of pulmonary reperfusion injury are "no-reflow" phenomenon, overcirculation from high pressure in pulmonary artery, and increased left ventricular end-diastolic pressure. Chronic hypoxia in cyanotic CHD eventually depletes endogenous antioxidant and increased the risk of pulmonary reperfusion injury, thus becoming a concern for palliative interventions in the oligaemic subgroup. The incidence of pulmonary reperfusion injury varies depending on multifactors. Despite its inconsistence occurrence, pulmonary reperfusion injury does occur and may lead to morbidity and mortality in this population. The current management of pulmonary reperfusion injury is supportive therapy to prevent deterioration of lung injury. Therefore, a general consensus on pulmonary reperfusion injury is necessary for the diagnosis and management of this complication as well as further studies to establish the use of novel and potential therapies for pulmonary reperfusion injury.

Complex cyanotic congenital heart disease and cervical spine surgery: Ticking all the right boxes.

Although complex congenital heart disease (CHD) patients usually present in childhood, it is not rare to see adults well past middle age. These patients undergo continuous pathophysiological changes in their heart and blood vessels, making anesthetic management more challenging if surgery is required. Herein, we report a case in which understanding the anatomy and pathophysiology helped optimally manage a patient with a double outlet right ventricle (DORV) who underwent plating and fixation for a hangman's fracture in the prone position.

[A case of Charcot-Marie-Tooth disease type 2 caused by homozygous MME gene mutation].

The patient is a 44-year-old man. His parents are consanguineous. He experienced muscle weakness in his toe and distal tingling sensation in his feet at 42 years of age, which gradually progressed. Additionally, a marked cyanotic discoloration of the feet appeared and worsened progressively. Neurological examination revealed loss of tendon reflexes and distal muscle weakness in the lower extremities. Findings from nerve conduction studies indicated axonal polyneuropathy. Upon detection of the MME gene mutation, the patient was diagnosed with autosomal-recessive Charcot-Marie-Tooth disease 2T (ARCMT2T). In this case, cyanosis of the lower extremities possibly was associated with ARCMT2T, and it was suggested to be due to neprilysin deletion linked with the MME mutation. This represents the first documented occurrence of cyanosis as a distinctive feature of CMT with MME mutation.

Unrepaired tetralogy of Fallot in a 71 years old woman: A case report and review of the literature.

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease (CHD) in infants. The four components that constitute ToF are an overriding aorta over the crest of the interventricular septum, obstruction in the right ventricular outflow tract, right ventricular hypertrophy, and a typically large non-restricted ventricular septal defect. ToF may also be associated with other extracardiac abnormalities, including patent ductus arteriosus or multiple aortopulmonary collateral arteries, which can impact the patient's survival. Patients with unoperated ToF rarely reach adulthood, and it is extremely rare to discover undiagnosed ToF in individuals over 60 years old. In this report, we describe an unusual case of a woman with unrepaired ToF who survived until the age of 71. She was fairly asymptomatic until the 7th decade of her life and complained only of dyspnea on exertion. The patient declined corrective cardiac surgery and preferred conservative management.

Novel transcatheter intervention for iatrogenic cyanosis due to surgical rerouting of inferior vena cava to the left atrium.

Improper identification of the atrial septal defect margins during surgery and inadvertent suturing of the surgical patch to the Eustachian valve of the inferior vena cava (IVC) results in the diversion of inferior venacaval blood to the left atrium causing cyanosis. This complication has been dealt so far with surgery. We report the planning and implementation of a novel transcatheter rediversion of the IVC to the right atrium using a covered stent.

Acquired Methemoglobinemia in the Surgical Intensive Care Unit.

Acquired methemoglobinemia is a potentially lethal medical condition caused by exposure to oxidizing xenobiotics, including antibiotics such as dapsone and inhaled anesthetics such as benzocaine. In this case report, we describe two presentations of acquired methemoglobinemia which presented to our surgical intensive care unit within one month. This highlights the potential connection between an emergent surgery or procedure and the development of methemoglobinemia in an environment where it is presumed that this condition would be extremely rare. High clinical suspicion for methemoglobinemia is warranted if the patient develops cyanosis or a decreased oxygen saturation unresponsive to supplemental oxygen when another etiology is not identifiable. If methemoglobinemia is suspected, a direct measurement of blood methemoglobin levels can be obtained to confirm the diagnosis. Prompt treatment with intravenous methylene blue is highly effective.

Long-term home mechanical ventilation using a noninvasive ventilator via tracheotomy in patients with myasthenia gravis: a case report and literature review.

Neuromuscular diseases (NMD) are indications for long-term home mechanical ventilation (HMV). Noninvasive ventilation is preferred to HMV. However, invasive mechanical ventilation (IMV) is more appropriate if the patient has uncontrollable airway secretions, the possibility of aspiration, failure to wean, or severe weakness of the respiratory muscles. But if the patient undergoes multiple intubation or tracheotomy, it will be more painful and unbearable. For some end-stage NMD patients who need long-term tracheostomy, HMV using noninvasive ventilator via tracheotomy may be a conservative care option. An 87-year-old male with myasthenia gravis underwent repeated IMV and failed to wean. We used a noninvasive ventilator connected to a tracheostomy tube for mechanical ventilation. One and a half years later, the patient weaned successfully. However, there was a lack of evidence-based medicine and standardized guidelines in such areas as indications, contraindications, and ventilator parameter setting. For the systematic review, a literature search was performed in PubMed, Embase, Cochrane, and CNKI (China National Knowledge Infrastructure) to identify reported cases of using noninvasive ventilator in patients undergoing tracheostomy. A total of 72 cases who performed ventilation via tracheotomy tube were identified. The main diagnoses included NMD, chronic obstructive pulmonary disease (COPD), pneumonia, and congenital central hypoventilation syndrome (CCHS). Indications included dysfunctional ventilatory weaning response (DVWR), apnea and cyanosis. Clinical outcome was as follows: 33 patients were weaned, and 24 patients underwent HMV. A total of 288 cases who performed ventilation through the mask after blocking the tracheostomy tube were identified. The primary diagnoses included COPD, NMD, thoracic restriction, spinal cord injured (SCI), and CCHS. Indications included DVWR, apnea and cyanosis, routine weaning. Clinical outcome was as follows: successful tracheostomy tube decannulations were performed in 254 patients and failed in 33 patients. So, in patients requiring HMV, selection of noninvasive ventilation (NIV) or IMV should be individualized. Tracheostomy preservation should be considered in some patients with advanced NMD if there is respiratory muscle weakness or the risk of aspiration. And attempts can be made to use a noninvasive ventilator because of its advantages of portability, ease of operation, and low cost. Noninvasive ventilators can be used in patients with tracheotomy, whether direct connection tracheotomy or mask ventilation after the tube is capped, especially in weaning and tracheostomy tube decannulation.

Novel Diabolo Configuration of a Large Covered Stent to Treat Cyanosis Related to Pulmonary Arteriovenous Malformations.

Microvascular pulmonary arteriovenous malformations (pAVMs) can lead to profound hypoxemia. "Hepatic factor" is postulated to play a role in their development. Certain patients with congenital heart disease are at particular risk to develop pAVMs, including those with heterotaxy syndromes and complex Fontan palliation. Ideally, an underlying cause is identified and corrected, although pAVMs may persist despite those interventions. We report a patient with heterotaxy syndrome s/p Fontan who had pAVMs that persisted despite Fontan revision with equal hepatic flow to both lungs. We employed a novel method to produce a diabolo configuration of a large covered stent to restrict lung flow while maintaining the potential for future dilation.

Can Isolated Discordant Atrioventricular Connections Survive Without Interatrial or Interventricular Shunt?

Clinical presentation of isolated discordant atrioventricular connections is akin to transposition of the great arteries. In the absence of a significant intracardiac shunt, profound cyanosis is expected at birth. We report one such 5-month-old infant who had only mild cyanosis. The left-sided tricuspid valve straddled the interventricular septum with a closed interventricular communication, a type of "Double Outlet Left Atrium with three atrioventricular valves," which provided the necessary "left to right" shunt while severe regurgitation through the straddling part and a patent ductus arteriosus provided the effective pulmonary blood flow.

Factors contributing to mortality in neonates with congenital diaphragmatic hernia and eventration.

Introduction: Despite all the advances, the mortality rate of congenital diaphragmatic hernia (CDH) ranges from 30% to 60% for isolated CDH and as high as 89% when they are associated with additional structural or chromosomal anomalies. Hence, a study was conducted to evaluate the factors contributing to the mortality of neonates treated for CDH or the eventration of diaphragm. Materials and Methods: A retrospective study was conducted in the department of paediatric surgery at a tertiary centre. The neonates admitted with a diagnosis of CDH or eventration requiring surgery, between March 2013 and March 2021, were included in the study. Results: A total of 123 neonates were included in the study. The variables, earlier median age at presentation (1 [1-23] vs. 3 [1-28]; P < 0.001; Mann-Whitney U-test), preterm birth (10/79 vs. 0/44; P = 0.01; Fischer's exact test), inborn (68/79 vs. 27/44; P = 0.002; Chi-square test), weight ≤2 kg (18/79 vs. 1/44; P = 0.003; Chi-square test), central cyanosis at presentation (21/79 vs. 1/44; P < 0.001; Chi-square test), antenatal detection (47/79 vs. 14/44; P = 0.003; Chi-square test) and earlier mean age at surgery (3.66 ± 1.47 vs. 7.66 ± 6.88; P < 0.001; Independent sample t-test) were associated with increased mortality. On multinominal logistic regression analysis, the factors preterm (odd's Ratio [OR] =4.735; P = 0.03), weight ≤2 kg (OR = 5.081; P = 0.02), central cyanosis at presentation (OR = 6.969; P = 0.008) and antenatal detection (OR = 7.471; P = 0.006) were found to be independently associated with increased mortality in CDH/eventration. Conclusion: The factors: prematurity, weight <2 kg, cyanosis at presentation and antenatal diagnosis were independently associated with increased mortality in neonates with CDH/eventration requiring surgery.

Causa inusual de cianosis en el recién nacido: hemoglobina M / Unusual cause of cyanosis in the newborn: hemoglobin M

Resumen La hemoglobina M es un desorden hereditario infrecuente, causante de metahemoglobinemia y, por ende, cianosis. Las manifestaciones clínicas de esta enfermedad son amplias y variadas, por lo que se debe considerar como diagnóstico diferencial en un recién nacido con cianosis sin otra causa aparente. A continuación, se presenta el caso de un recién nacido de 5 horas de vida con cianosis generalizada desde el nacimiento y con saturaciones de oxígeno de entre 60-70%, en el que se descartaron patologías como hipoxia perinatal, patología pulmonar o cardíaca y sepsis y se documentó un nivel de metahemoglobina elevado, reportado en 21,6%, con lo cual se estableció el diagnóstico de metahemoglobinemia. El tratamiento administrado fueron dos dosis de azul de metileno, pero no hubo respuesta clínica. Por este motivo, se realizó electroforesis de hemoglobina, la cual fue compatible con hemoglobina M (Iwate o Kankakee), lo que se confirma su causa congénita de metahemoglobinemia.

Abstract Hemoglobin M is a rare hereditary disorder that causes ethemoglobinemia and therefore cyanosis. The clinical manifestations of this condition differs considerably, so it should be considered as a differential diagnosis in a newborn with cyanosis, with no other apparent cause. The case of a 5 hours old newborn is presented below, with generalized cyanosis from birth with oxygen saturations between 60-70%, in whom, upon ruling out pathologies such as perinatal hypoxia, pulmonary disease, heart disease and sepsis, a high level of methemoglobin is documented, reported in 21,6%; the diagnosis of methemoglobinemia was established. The treatment administered was two doses of methylene blue with no response. For this reason, hemoglobin electrophoresis was performed, which was compatible with Hemoglobin M (Iwate or Kankakee), confirming its congenital cause.

[Oculo-facio-cardio-dental syndrome caused by BCOR gene mutations: a case report]. / BCORåŸºå› çªå˜è‡´æ–°ç”Ÿå„¿çœ¼-面-心-牙综合征1例.

A full-term female infant was admitted at 5 hours after birth due to heart malformations found during the fetal period and cyanosis once after birth. Mmultiple malformations of eyes, face, limbs, and heart were noted. The whole-exome sequencing revealed a pathogenic heterozygous mutation, c.2428C>T(p.Arg810*), in the BCOR gene. The infant was then diagnosed with oculo-facio-cardio-dental syndrome. He received assisted ventilation to improve oxygenation and nutritional support during hospitalization. Right ventricular double outlet correction was performed 1 month after birth. Ocular lesions were followed up and scheduled for elective surgery. The possibility of oculo-facio-cardio-dental syndrome should be considered for neonates with multiple malformations of eyes, face, and heart, and genetic testing should be performed as early as possible to confirm the diagnosis; meanwhile, active ophthalmic and cardiovascular symptomatic treatment should be given to improve the prognosis.

[A family with early onset myopathy caused by MEGF10 gene defect and literature review].

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.