Project description:Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.
Project description:BackgroundMitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a multi-organ disorder resulting from mitochondrial DNA (mtDNA) mutations. We report a case of suspected MELAS syndrome that progressed to left ventricular dysfunction 24 years after an initial diagnosis of atrioventricular block (AVB).Case summaryA 51-year-old woman was referred to heart failure clinic because of dyspnoea on exertion and progressive cardiomegaly. She had a dual-chamber pacemaker implanted for 24 years because of a high-degree AVB. She was treated for diabetes mellitus for 23 years and used hearing aids for 12 years because of sensorineural hearing loss. Transthoracic echocardiography revealed reduced left ventricular ejection fraction (26%), with increased thickness and unusual texture of the myocardium. The absence of abnormal findings on serum and urine protein electrophoresis suggested that light-chain amyloidosis was unlikely. In addition, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy revealed no definite uptake in the myocardium. Endomyocardial biopsy revealed a hypertrophy of myocytes in haematoxylin-eosin staining, and electron microscopy revealed a disarrangement of mitochondrial cristae, which were suggestive of mitochondrial cardiomyopathy. A mtDNA test detected the m.3243A > G mutation in the MT-TL1 gene. According to these findings, MELAS syndrome was the most probable diagnosis despite the absence of common symptoms such as stroke-like episodes or lactic acidosis.DiscussionThe patient had progressed to heart failure with reduced ejection fraction 24 years after the first cardiac manifestation. An identification of the mutation in the MT-TL1 gene, indicative of MELAS syndrome, enabled the diagnosis of MELAS syndrome without typical manifestations.
Project description:Pediatric endocarditis, a rare entity in developed countries, remains a challenging diagnosis to make in children. We present an uncommon etiology of shortness of breath on exertion (SOBOE) in a 7-year-old male presenting with two weeks of nocturnal fever, malaise and fatigue following a viral prodrome. Point of care ultrasound (POCUS) led to suspicion for a ventricular septal defect (VSD) with tricuspid valve (TV) endocarditis, which was ultimately confirmed by formal echocardiography. This ultrasound diagnosis allowed emergency clinicians to order blood cultures under the suspicion of endocarditis as well as expedited antibiotic treatment.
Project description:BackgroundTetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. It is generally diagnosed and surgically repaired early in life, with good overall outcomes.Case presentationWe report the case of a patient incidentally diagnosed with paucisymptomatic TOF at the age of 56 years old, during investigations for carbon monoxide poisoning. The patient had a history of thyroidectomy, arterial hypertension, and four uncomplicated vaginal deliveries.ConclusionsThis case shows us that some patients with TOF can reach older ages without surgical correction. Late surgical repair should be meticulously decided on a case basis.
Project description:Mosaicism for FMR1 premutation (PM: 55-199 CGG)/full mutation (FM: >200 CGG) alleles or the presence of unmethylated FM (UFM) have been associated with a less severe fragile X syndrome (FXS) phenotype and fragile X associated tremor/ataxia syndrome (FXTAS)-a late onset neurodegenerative disorder. We describe a 38 year old male carrying a 100% methylated FM detected with Southern blot (SB), which is consistent with complete silencing of FMR1 and a diagnosis of fragile X syndrome. However, his formal cognitive scores were not at the most severe end of the FXS phenotype and he displayed tremor and ataxic gait. With the association of UFM with FXTAS, we speculated that his ataxia might be related to an undetected proportion of UFM alleles. Such UFM alleles were confirmed by more sensitive PCR based methylation testing showing FM methylation between 60% and 70% in blood, buccal, and saliva samples and real-time PCR analysis showing incomplete silencing of FMR1. While he did not meet diagnostic criteria for FXTAS based on MRI findings, the underlying cause of his ataxia may be related to UFM alleles not detected by SB, and follow-up clinical and molecular assessment are justified if his symptoms worsen.
Project description:Case presentationA 56-year-old man presented to the lung nodule clinic with abnormal chest imaging prompted by a chronic cough and hemoptysis. Approximately 2.5 years earlier, while kneeling beside his car fixing a flat tire, he fell backwards while holding the tire cap in his mouth, causing him to inhale sharply and aspirate the cap. He immediately developed an intractable cough productive of flecks of blood. He presented to an emergency room but left before being seen because of a long wait time and his lack of health-care insurance. He self-medicated for severe cough and chest discomfort with codeine, eventually developing a dependency. Approximately 3 weeks after aspirating the tire cap, his cough became productive, and he developed fever and chills. His symptoms improved transiently with antibiotics and additional narcotics. Ultimately, his chronic cough with intermittent hemoptysis affected his ability to work, and 30 months later he sought medical attention and was diagnosed with pneumonia and reactive airway disease. He was prescribed doxycycline, steroids, inhaled albuterol, and dextromethorphan, with initial improvement, but his symptoms recurred multiple times despite quitting smoking, leading to repeated medication courses.