Classic Triad Research Articles

Steroid-resistant nephrotic syndrome due to renal-limited thrombotic microangiopathy and membranous nephropathy after allogeneic hematopoietic stem cell transplantation successfully treated with calcineurin inhibitors.

Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown. Herein, we report three cases of renal-limited TMA after allo-HSCT that presented with nephrotic syndrome, in which renal biopsy showed TMA and concurrent membranous nephropathy. All patients were refractory to glucocorticoid monotherapy and the addition of CNIs led to complete remission of nephrotic syndrome. Renal-limited TMA after allo-HSCT may present as nephrotic syndrome with distinct pathophysiological features from renal-limited TMA in non-allo-HSCT recipients. Previous reports have suggested that renal-limited TMA after allo-HSCT is associated with renal graft-versus-host disease, and thus optimizing immunosuppressive therapy, including CNI treatment, may be useful. CNI treatment may be an option even in the presence of renal-limited TMA after allo-HSCT accompanied by concurrent membranous nephropathy.

Co-presentation of diabetic ketoacidosis and hepatitis an infection with anasarca: a case report

Diabetic ketoacidosis is the common initial presentation of Type 1 Diabetes Mellitus in paediatric practice. Hepatitis A infection is a common cause of jaundice in children with varied constitutional symptoms. However, co-presentation of diabetic ketoacidosis and hepatitis A infection with anasarca is rare. One four-year-ten-month-old male child presented to the emergency department of our hospital with diabetic ketoacidosis with new-onset Type 1 diabetes mellitus. At the time of presentation, the blood sugar level was in the diabetic range, 677 mg% laboratory value and was suggestive of diabetes mellitus. The HbA1c level was 14.47% at that time; however, there was no history of the classical triad of polyuria, polydipsia and polyphagia in the child. The child presented with mild acidosis (pH 7.3) and responded to the Milwaukee regimen of DKA management. During the course of the management, the child developed clinical jaundice on the 5th day of hospital admission and was investigated and diagnosed as having viral hepatitis A. On the 7th day of illness, the child developed anasarca in the form of moderate pleural effusion and gross ascites, leading to respiratory distress along with pedal edema and scrotal edema. The anasarca responded to symptomatic treatment and the clinical improvement of Hepatitis A occurred after 15 days. The stressful event of brewing hepatitis A, precipitating DKA in a relatively asymptomatic child of type 1 diabetes mellitus, is more likely in our case. The chance association of both the conditions in an underweight child with a history of 3rd degree consanguinity is noted in our child. The child also developed anasarca, which is uncommon in viral hepatitis A or diabetic ketoacidosis alone.

Inherited or Immunological Thrombocytopenia: The Complex Nature of Platelet Disorders in 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is one of the most common congenital malformation syndromes resulting from disrupted embryonic development of pharyngeal pouches. The classical triad of symptoms described by Angelo DiGeorge is frequently accompanied by hematological and immune disorders. While it is well-established that patients with 22q11.2DS have an increased risk of recurrent autoimmune cytopenias, including immune thrombocytopenia, the platelet abnormalities in this population are more complex and multifaceted. Given this issue, we conducted a comprehensive literature review on platelet disorders in 22q11.2DS using accessible databases (PubMed and Scopus). We aimed to outline previous studies limitations and most urgent challenges concerning thrombocytopenia in these patients. One characteristic finding frequently observed in 22q11.2DS is mild macrothrombocytopenia caused presumably by the loss of one GP1BB allele, encoding the element of the GPIb-IX-V complex. This structure plays a central role in thrombocyte adhesion, aggregation, and subsequent activation. Recent studies suggest that defective megakaryopoiesis and impaired vasculogenesis may strongly influence platelet and hemostasis disorders in 22q11.2DS. Furthermore, the phenotypic manifestation may be modulated by epigenetic factors and gene expression modifiers located outside the deletion region. Although the final hemorrhagic phenotype is typically mild, these patients may require more frequent transfusions following major surgical procedures. Despite the risk of thrombocytopenia and thrombocytopathy, there is a lack of large-scale research on hematological anomalies in 22q11.2DS, and the available results are often inconclusive. Given the complexity of hemostatic disorders, it is essential to establish specific recommendations for perioperative management and autoimmune cytopenias treatment within this population.

A Distinctive Encounter With Diffuse Alveolar Hemorrhage in Granulomatosis With Polyangiitis and Pneumonia.

This article highlights the critical importance of identifying the classic triad of hemoptysis, anemia, and diffuse pulmonary infiltrates, offering clinicians a structured approach for the timely diagnosis and management of the diffuse alveolar hemorrhage in setting of GPA. Post-intubation HRCT findings revealed diffuse patchy ground glass opacities in both lungs, along with right lobar consolidation showing liquefaction and an air-fluid level.

Clinical masks of primary cardiac tumors: a clinical case report

INTRODUCTION: Primary cardiac tumors are rare, 75% of them are benign, half of which are myxomas. Despite histological benignity, untimely diagnosed myxoma can have serious complications. Myxoma is characterized by non-specific symptoms, however, a typical triad of atrial myxoma symptoms is distinguished: (1) symptoms of mitral valve obstruction manifested by heart failure and weakness, (2) symptoms of embolism and (3) systemic manifestations. AIM: Illustration of the variety of clinical manifestations, discussion of diagnostic difficulties, formation of clinical alertness in the observation of left atrial myxoma. MATERIALS AND METHODS: Left atrial myxoma in a 49-year-old male patient debuted at the age of 44 with the development of a transient cerebrovascular disorder in the right carotid system manifested by dysarthria and paresis of the facial muscles; at that time, no echocardiographic (EchoCG) examination was conducted. Several years later, the clinical presentation of heart failure manifested: shortness of breath when walking, edema of lower limbs. EchoCG revealed a sizable mass in the left atrium 33 mm × 55 mm fixed to the interatrial septum, prolapsing into the left ventricle and partially stenosing the left atrioventricular opening. Dilation of both atria, of the right ventricle, pronounced pulmonary hypertension, 2-degree regurgitation on the tricuspid valve, 2-degree regurgitation on the pulmonic valve, hydropericardium and hydrothorax on the right were found. The clinical case was also characterized by the developed bilateral thrombosis of the superficial femoral vein with signs of flotation. The development of venous thrombosis in a patient with cardiac myxoma can probably be considered as a systemic manifestation of the tumor disease. After compensation for the heart failure and implantation of a cava filter, the tumor was surgically removed, the morphological picture corresponded to cardiac myxoma with hemorrhages of various ages. CONCLUSION: The case demonstrates the need for performing EchoCG in a transient ischemic attack, in ischemic stroke, to screen for intracardiac masses capable of frustrating cerebral circulation by cardioembolic mechanism, especially at a young age in the absence of other cardiovascular risk factors. The clinical picture consistently showed all the symptoms of the classic triad of cardiac myxoma: embolic syndrome, symptoms of mitral valve obstruction and systemic manifestations. The prognosis for patients with cardiac myxoma depends on the severity of thromboembolic syndrome and severity of heart failure. Timely diagnosis and surgical removal of cardiac myxoma provide a favorable prognosis.

Pregnancy vomiting obscuring other disease: a clinical case of Wernicke encephalopathy

The article presents a clinical case of Wernicke encephalopathy occurring as complication of excessive pregnancy-related vomiting (hyperemesis gravidarum). This disorder has developed due to thiamine (vitamin B1) deficiency. The correct diagnosis is challenging due to the similarity of clinical manifestations with several other disorders. Timely diagnosis and early treatment reduce the risk of severe course and irreversible complications that can lead to the potentially adverse outcome. This case is remarkable due to the appearance of the disease in a 32-year-old pregnant woman with excessive vomiting. The patient demonstrated the classic symptom triad found in only 16% of patients with Wernicke encephalopathy. Primarily ataxia and nystagmus appeared, and later memory impairment with confabulations was recorded. Magnetic resonance imaging of the brain revealed bilateral symmetrical areas with increased MR signal intensity in T2 (SE and FLAIR) sequences in the mediodorsal nucleus (MD) of thalamus, subependymal microglia of the III ventricle, and periaqueductal gray. The treatment of Wernicke encephalopathy was immediately initiated with the use of intravenous thiamine 200 mg 3 times daily. The beneficial treatment effect was reported. Further pregnancy proceeded unremarkably and resulted in the birth of a live term girl. During the postpartum period, the patient reported persisting instability when walking, which increased with closed eyes, and non-systemic dizziness.

Isolated Right Atrial Enhancement with Atrial Standstill: An Uncommon Presentation of Emery–Dreifuss Muscular Dystrophy

AbstractEmery–Dreifuss muscular dystrophy (EDMD) is a rare inherited syndrome that affects muscles, joints, and the heart. The classic clinical triad includes early joint contractures, slowly progressive muscle weakness, and cardiac abnormalities. The common cardiac manifestations include conduction disturbances, systolic dysfunction, and dilated cardiomyopathy and may be associated with left ventricular noncompaction with an increased risk of thromboembolic events. Conduction disturbances include atrial arrhythmias, atrial standstill, complete heart block, or ventricular tachyarrhythmia. Cardiac magnetic resonance imaging (CMR) can help in the diagnosis of this condition by identifying chamber dilatation, systolic dysfunction, and late gadolinium enhancement of the atrium. Additional MRI finding of paraspinal muscle atrophy, an important finding in this muscular dystrophy, helped in reaching a confident imaging diagnosis. Our case in this article highlights the clinical and CMR findings of this rare condition.

West Syndrome: spectrum of disorders with diagnostic and therapeutic challenges

Introduction: West syndrome (WS) is a rare epileptic encephalopathy of multifactorial etiology, characterized by epileptic spasms, psychomotor delay, and hypsarrhythmia on electroencephalogram. Its prevalence is 1.5 to 2 per 10,000 children under 10 years, with an incidence of 1 per 2,000-4,000 live births. Objective: This article describes the clinical characteristics of a pediatric patient with WS in a developing country context. Materials and methods: With informed consent, the clinical history was performed, detecting psychomotor delay at 6 months, manifested by loss of social smile and gross motor skills. Physical examination revealed generalized hypotonia, desaturation, and bradycardia. Neuroimaging ruled out organic abnormalities; however, the electroencephalogram (EEG) showed hypsarrhythmia, confirming the diagnosis of West syndrome by meeting the classic clinical triad. Results and discussion: Male patient of 6 months, firstborn, born by cesarean section at 39 weeks due to hypoxic encephalopathy, with negative STORCH and toxicological tests. He presented to the emergency room with four episodes of spastic movements in the upper limbs, which spontaneously resolved without loss of consciousness, during the previous month. Currently, at 12 years old, the patient is in remission, without seizure episodes for over 10 years. He shows adequate social and family adaptation, with academic performance appropriate for his age group. Cognitive tests indicate borderline performance, suggesting the presence of ADHD, with no evidence of underlying cognitive deficit.

Horner Syndrome in a Pediatric Patient: A Case Report of Lymphatic Malformation Induced Presentation in a 7-year-old Boy

Lymphatic malformations are low-flow vascular anomalies that predominantly affect the cervicofacial region in the pediatric population. We describe a case of a 7-year-old healthy boy who presented to the emergency department with the classic triad of miosis, ptosis, and anhidrosis. Initial evaluation, including a cervicocranial computed tomography scan, revealed no intracranial space-occupying lesion. Subsequent diagnostic work-up, involving ultrasound and cervicothoracic magnetic resonance imaging, identified a cystic lesion in the upper mediastinum, consistent with the diagnosis of lymphatic malformations. The integration of a multidisciplinary team proved essential in reaching a definitive diagnosis and selecting the optimal treatment (ultrasound-guided sclerotherapy) mitigating the risk of life-threatening and cosmetic complications.

Hepatic Vein Thrombosis Secondary to Protein C and S Deficiency

Hepatic Venous Outflow Tract Obstruction is obstruction of the hepatic venous outflow tract can be primary due to obstruction by thrombosis or secondary due to compression of hepatic vein, inferior vena cava or both. Causes being prothrombotic inherited or acquired. Classical clinical triad being abdominal pain, ascites, and tender hepatomegaly.Ultrasound, Computed Tomography or Magnetic Resonance Imaging of abdomen are required for confirmation.Long-term anticoagulation with vitamin K antagonists should be started. 24year female with abdominal distention and pain, having pallor, fluid distended abdomen. CT abdomen revealed an hypodense focal lesion in right lobe, ascites with Hepatic Vein Thrombosis. Haematology Low Functional antithrombin activity of 29 units, low Free Protein S Antigen of 42.8 units, very low Protein C functional activity of 16.5 units was observed. Frequency of prothrombotic hepatic venous outflow tract obstruction in India is more compared to west. So considered in all cases with acute, chronic liver disease with complications.

Wernicke's Encephalopathy

Wernicke encephalopathy is a thiamine deficiency condition that has a wide range of somatic causes in addition to alcohol abuse. Most patients do not have the classical clinical triad — oculomotor dysfunction, ataxia and cognitive impairment at the onset of the disease, which makes timely diagnosis difficult. The disease may manifest as dizziness, unsteadiness, double vision, or cognitive impairment. Key clinical manifestations include symmetrical gaze-evoked nystagmus, truncal ataxia, bilateral abducens paresis, internuclear ophthalmoplegia, bilateral vestibular-ocular reflex reduction, and anterograde amnesia. To make a diagnosis, the presence of a condition leading to thiamine deficiency is required. The diagnosis is confirmed by MRI, but even with clinical suspicion of Wernicke encephalopathy, it is necessary to initiate parenteral therapy with thiamine in an adequate dose. With timely treatment, the disease has a good prognosis.

A Brief Review on Normal Pressure Hydrocephalus Diagnosis in Primary Neuropsychiatric Care Settings

Normal pressure hydrocephalus (NPH) is clinically characterized by the triad of mental deterioration, gait disturbance, and urinary incontinence. Correct diagnosis and referral of patients is important because NPH is a potentially treatable cause of cognitive decline and should be distinguished from more common forms of irreversible dementia. Unfortunately, it remains to be a rather underdiagnosed and controversial neuropsychiatric entity even in countries with modern healthcare systems. The diagnostic process is complicated by diverse clinical presentations, especially when the classical triad is incomplete or atypical such as with psychiatric symptoms. This manuscript aims to briefly review atypical clinical presentations of NPH and basic radiologic findings associated with it, and outline some recommendations to primary care physicians for diagnosis and referral.

Decoding the Risks of Fecal Incontinence: A Comprehensive Analysis of Closed Internal Sphincterotomy in Chronic Anal Fissure.

Introduction An anal fissure is marked by a longitudinal tear in the mucosal lining of the lower anal canal, causing painful defecation and mild anal bleeding. The classical triad includes an anal ulcer, a sentinel tag, and a hypertrophic papilla. This study investigates the frequency of fecal incontinence in patients with anal fissure undergoing closed internal sphincterotomy, offering recent insights for treatment recommendations. Objective To determine the prevalence of fecal incontinence in individuals with chronic anal fissure undergoing closed internal sphincterotomy. Methodology The study design was a descriptive case series, conducted over a 6-month period (August 21, 2018 to February 21, 2019). It was carried out at the General Surgery Department, Lady Reading Hospital MTI, Peshawar, Pakistan. The participants included a total of 139 patients diagnosed with chronic anal fissures. Data collection To gather comprehensive information, a detailed approach was adopted. This included history taking, general physical examinations, and digital rectal examinations for all patients. All patients diagnosed with chronic anal fissure were prepared for lateral internal sphincterotomy (LIS). Variables The variable of interest was the occurrence of fecal incontinence, assessed during follow-up visits at the end of the 2nd and 6th week post-surgery. Ethical consideration The study received approval from the hospital's ethical committee and the College of Physicians and Surgeons of Pakistan (CPSP) research committee. Results In our study, the mean age was 30 years (SD ± 12.16). Forty-five percent of patients were male, and 55% were female. Fecal incontinence was observed in 10% of patients. Conclusion Our study reveals a fecal incontinence frequency of 10% in patients undergoing closed LIS for chronic anal fissure.

Antepartum Wernicke’s Encephalopathy: Common, and Yet Rarely Diagnosed. Discussion on the Disease and Its Treatment

This review article presents a comprehensive discussion on antepartum Wernicke’s encephalopathy (WE), a serious neurological disorder. This disorder stems from thiamine (Vitamin B1) deficiency, which is critical for normal metabolism and neuronal integrity. During pregnancy, women are more susceptible to this condition due to increased nutritional requirement and metabolic changes. In WE, inadequate thiamine (Vitamin B1) causes disruption of metabolism in cells and impedes neurotransmitter synthesis in the brain, ultimately causing adverse neural consequences. Key risk factors contributing to antepartum WE include conditions that hinder thiamine absorption or increase metabolic demand, such as hyperemesis gravidarum (intense antepartum vomiting), malnutrition, alcoholism, and post-bariatric surgery states. WE's classic triad of symptoms, confusion, ataxia (loss of balance and coordination), and ophthalmoplegia (occlumotor incoordination), are not commonly seen in antepartum WE. Therefore, diagnosing the disorder in pregnancy is challenging and the condition is often misdiagnosed. Pregnancy symptoms like nausea, vomiting, and fatigue often overlap with WE's presentation, complicating diagnosis and confounding treatment. While magnetic resonance imaging (MRI) can reveal characteristic lesions in brain areas such as the thalamus and mammillary bodies, these may not always appear in early stages, adding further diagnostic difficulty. Effective management of antepartum WE relies on early recognition and timely administration of high-dose thiamine, particularly parenteral administration for affected pregnant women. Prompt treatment is critical to preventing irreversible sequalae, neurological and otherwise in both the woman and the child. Once acute symptoms are managed, transitioning to oral thiamine supplementation is the norm to prevent recurrence and maintain normal thiamine levels. Balanced diet of macro-nutrients and maintaining fluid and electrolyte balance, also plays an essential role in recovery. In severe or treatment-resistant cases, more intensive, prolonged thiamine therapy and regular monitoring of maternal and fetal health are necessary, usually managed by a multidisciplinary medical team. This coordinated care approach aims to prevent recurrence and minimize risks associated with WE. The article emphasizes following clinical guidelines, which recommend regular thiamine monitoring and preventive measures in high-risk pregnancies, to improve maternal and fetal outcomes. By adhering to established protocols, healthcare providers can reduce the likelihood of severe complications associated with WE, ensuring better care and recovery for affected pregnant women. Categories: Pregnancy, Neurology, Nutrition.

Exploring the Spectrum of Comorbidities Associated with Primary Aldosteronism: Insights from a Large Real-World Case-Control Study.

Background: Primary aldosteronism (PA) is a common cause of endocrine hypertension, characterized by excessive aldosterone secretion leading to hypertension, hypokalemia, and metabolic alkalosis. While historically diagnosed based on this classic triad of symptoms, current understanding reveals a more nuanced presentation. This study aimed to investigate the prevalence of PA-associated diseases in a large German population. Methods: Medical records from the IQVIATM Disease Analyzer database were analyzed retrospectively. PA patients (n = 860) were matched with non-PA individuals (n = 4300) by age and sex. Associations between PA and predefined chronic diseases were examined using multivariable logistic regression. Results: PA was significantly associated with hypokalemia (7.8% vs. 1.6%, odds ratio (OR): 3.45; 95% confidence intervals (CIs): 2.41-4.96), hypertension (56.1% vs. 28.5%; OR: 2.37; 95% CIs: 2.00-2.81), hepatic steatosis (11.3% vs. 3.0%; OR: 1.85; 95% CIs: 1.34-2.57), gout (8.3% vs. 2.2%; OR: 1.64; 95% CIs: 1.15-2.35), chronic kidney disease (6.3% vs. 2.2%; OR: 1.59; 95% CIs: 1.10-2.31), diabetes mellitus not otherwise specified (7.9% vs. 2.9%; OR: 1.49; 95% CIs: 1.06-2.09), obesity (13.5% vs. 5.1%; OR: 1.38; 95% CIs: 1.05-1.82), and depression (14.8% vs. 6.2%; OR: 1.37; 95% CIs: 1.07-1.77). Conclusions: While the study design had limitations, including reliance on ICD codes for diagnosis, these findings underscore the critical need for early detection and personalized management strategies for PA to reduce associated risks and improve patient outcomes.

'Great Masquerader': a history of diagnosing pheochromocytoma.

Pheochromocytoma is a unique tumour with a variety of clinical presentations. Coined as 'the great masquerader', it can present with the classical triad of headache, sweating and tachycardia and sometimes in an acute hypertensive crisis. This paper describes the evolutionary history of the diagnosis of this condition. A literature review was conducted using Medline Database from 1900 to 2023 outlining the methods of diagnosis for pheochromocytoma. There have been diagnostic dilemmas and localization challenges of pheochromocytoma over the last century. From the first description of pheochromocytoma in 1886 to the first successful resection in 1926, there was poor recognition of its atypical symptoms and lack of reliable diagnostic tests. Over the next few decades, there were significant advances in screening and biochemical tests. Further understanding of catecholamine release and metabolic pathways led to the development of tests to identify end products of catecholamine metabolism in plasma and urine. Computed imaging however heralded significant improvement in surgical planning and management. The evolution of histopathological diagnosis with the use of immunostains and genetic testing has further contributed to the identification of malignant pheochromocytomas and an understanding of their behaviours. Significant advances in the biochemical and imaging have shaped our understanding of pathophysiology and management. These diagnostic advances have enabled early and accurate detection and localization of pheochromocytomas to enable prompt surgical management.

Subependymal giant cell astrocytoma in the absence of tuberous sclerosis: a case report and literature review

Introduction and Importance: Subependymal giant cell astrocytoma (SEGA) is a benign intraventricular tumor classically arising near the Foramen of Monro. SEGAs almost always present as a component of tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by lesions in multiple organs. Case Presentation: A 16-year-old male with no significant past medical history presented with headache and dizziness. Imaging revealed intraventricular mass within the left lateral ventricle; the post-contrast image showed a contrast-enhanced lesion suggestive of SEGA. Following resection, histopathological analysis identified the lesion as a SEGA. However, on further workup, the patient was found not to meet the clinical criteria of TSC, which exemplifies a rare case of SEGA in the absence of a TSC diagnosis. Clinical Discussion: Tuberous sclerosis Complex (TSC) is a neurocutaneous disorder with a classical triad of seizures, mental retardation, and hamartomas in multiple organs and tissues. SEGA without TSC does not have multiorgan problems and hence doesn’t need ancillary testing but despite having a good outlook still needs follow-up for interval growth or recurrence. However, overall prognosis of isolated SEGA is better than SEGA associated with TSC. Conclusion: SEGA is commonly found to be associated with TSC. Although it is challenging to diagnose isolated SEGA, hence it is essential for physicians to be aware of the possibility of SEGA in the absence of other characteristics of TSC, which has many implications for a patient’s clinical course. This case report adds to current knowledge regarding isolated SEGA.

Electrocardiographic Clues for Early Diagnosis of Ventricular Pre-Excitation and Non-Invasive Risk Stratification in Athletes: A Practical Guide for Sports Cardiologists.

Ventricular pre-excitation (VP) is a cardiac disorder characterized by the presence of an accessory pathway (AP) that bypasses the atrioventricular node (AVN), which, although often asymptomatic, exposes individuals to an increased risk of re-entrant supraventricular tachycardias and sudden cardiac death (SCD) due to rapid atrial fibrillation (AF) conduction. This condition is particularly significant in sports cardiology, where preparticipation ECG screening is routinely performed on athletes. Professional athletes, given their elevated risk of developing malignant arrhythmias, require careful assessment. Early identification of VP and proper risk stratification are crucial for determining the most appropriate management strategy and ensuring the safety of these individuals during competitive sports. Non-invasive tools, such as resting electrocardiograms (ECGs), ambulatory ECG monitoring, and exercise stress tests, are commonly employed, although their interpretation can sometimes be challenging. This review aims to provide practical tips and electrocardiographic clues for detecting VP beyond the classical triad (short PR interval, delta wave, and prolonged QRS interval) and offers guidance on non-invasive risk stratification. Although the diagnostic gold standard remains invasive electrophysiological study, appropriate interpretation of the ECG can help limit unnecessary referrals for young, often asymptomatic, athletes.

Fanconi anemia diagnosed by genetic testing

Background : Fanconi anemia (FA) is a rare genetic disorder inherited in an autosomal recessive manner. The clinical phenotype varies depending on the involvement of different genes. Major physical abnormalities mainly affect the limbs and spine.. Methods/Observation : We report the case of an 11-year-old girl from a first-degree consanguineous marriage. The classic triad of short stature, malformation syndrome and early bone marrow failure suggested AF, which was confirmed by the detection of significant chromosomal instability after culture with Mitomycin C, compared with a normal control. Conclusion : This case highlights the crucial role of cytogenetics in the diagnosis of Fanconi anemia and genetic counseling to improve the management of affected children and their families. Keywords : Fanconi anemia; chromosomal breaks; mitomycin C.

Spinal Diffuse Midline Glioma H3 K27M-Altered: Report of a Rare Tumor with Extracranial Skeletal Metastases and Review of Literature.

Diffuse midline glioma, H3 K27-altered is a rare and aggressive pediatric brain tumor with a grim prognosis. Diffuse midline glioma is characterized by specific molecular alterations, including H3 K27 mutations, and involves deep midline structures such as the brainstem, cerebellum, spinal cord, and thalamus. These tumors present with a classic triad of symptoms and have limited surgical options due to their challenging locations. Extra-neural metastases are an unusual occurrence in diffuse midline glioma and have been rarely described. Here we report a 17-year-old girl with spinal diffuse midline glioma, H3 K27M-mutant, who presented with multiple metastatic osseous lesions confirmed on biopsy of the thoracic vertebral lesion. Due to the rapid disease progression, the patient was recommended palliative therapy. Extra-neural metastases in diffuse midline glioma are rare, with only 16 reported patients, and no standard therapy exists. An accurate and early diagnosis is necessary to develop a personalized plan of treatment. Further research is needed to gain insights into the molecular pathology of diffuse midline glioma, H3 K27-altered, and improve the quality of life and the outcome of patients with this deadly disease.