Case Report: Long-Term Suppression of Paroxysmal Kinesigenic Dyskinesia After Bilateral Thalamotomy

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by transient dyskinetic movements, including dystonia, chorea, or both, triggered by sudden voluntary movements. Carbamazepine and other antiepileptic drugs (AEDs) are widely used in the treatment of PKD, and they provide complete remission in 80–90% of medically treated patients. However, the adverse effects of AEDs include drowsiness and dizziness, which interfere with patients' daily lives. For those with poor compatibility with AEDs, other treatment approaches are warranted.Case Report: A 19-year-old man presented to our institute with right hand and foot dyskinesia. He had a significant family history of PKD; his uncle, grandfather, and grandfather's brother had PKD. The patient first experienced paroxysmal involuntary left hand and toe flexion with left forearm pronation triggered by sudden voluntary movements at the age of 14. Carbamazepine (100 mg/day) was prescribed, which led to a significant reduction in the frequency of attacks. However, carbamazepine induced drowsiness, which significantly interfered with his daily life, especially school life. He underwent right-sided ventro-oral (Vo) thalamotomy at the age of 15, which resulted in complete resolution of PKD attacks immediately after the surgery. Four months after the thalamotomy, he developed right elbow, hand, and toe flexion. He underwent left-sided Vo thalamotomy at the age of 19. Immediately after the surgery, the PKD attacks resolved completely. However, mild dysarthria developed, which spontaneously resolved within three months. Left-sided PKD attacks never developed six years after the right Vo thalamotomy, and right-sided PKD attacks never developed two years after the left Vo thalamotomy without medication.Conclusion: The present case showed long-term suppression of bilateral PKDs after bilateral thalamotomy, which led to drug-free conditions.

Heterozygous Familial Hyperlipidemia in a Fighter Pilot

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disease characterized by elevated low-density lipoprotein cholesterol (LDL-C) that increases risk for clinically significant atherosclerotic cardiovascular disease (ASCVD). This common (1:220) disease is present within the fighter pilot community and hesitation to treat this condition at younger ages results in a higher risk for coronary artery disease (CAD), the presence of which can be catastrophic for flying safety. CASE REPORT: A 40-yr-old asymptomatic F-15 pilot presented with persistently elevated LDL-C levels > 190 mg dL1 and a significant family history of CAD. Coronary artery calcium, CT angiography, and finally, invasive angiography were used to further stratify him as having mild CAD. Initiation of statin therapy significantly lowered his LDL and subsequent risk for disease progression, allowing him to return to flying. DISCUSSION: Early recognition and treatment of HeFH is imperative for lowering the risk of ASCVD. Often the medical community supporting flyers is hesitant to diagnose or treat this condition, due to nonrecognition, the young age of presentation, or reluctance to potentially ground a flyer. By intervening earlier, rather than waiting, aviators can remain on flying status longer with lower risk to themselves and their aircrew. Gatzke LC. Heterozygous familial hyperlipidemia in a fighter pilot. Aerosp Med Hum Perform. 2021; 92(10):835837.

Compound heterozygote KCNQ1 mutation causing Jervell Lange Neilson syndrome: a case report of genotype-phenotype correlation

Congenital sensorineural hearing loss (SNHL) is a common phenomenon with several genetic and non-genetic associations that require early diagnosis and work-up to prompt appropriate interventions. Of the genetic associations, Jervell and Lange-Nielsen syndrome (JLNS) remains a rare monogenic disease that is characterized by SNHL, prolongation of QT interval, syncopal attacks due to ventricular arrhythmias and sudden cardiac death from very early in life. We hereby report a 5 years old girl with SNHL and recurrent blackout episodes in early childhood with significant family history, admitted for cochlear implant who developed ventricular arrhythmias requiring multiple interventions with further investigations revealing a prolonged QT interval on electrocardiography (ECG) with metabolic abnormalities (hypomagnesemia and hypokalemia). Her clinical exome study showed a compound heterozygous KCNQ1 mutation, a more sporadic form of JLNS managed using oral beta-blocker. This experience illustrates the relevance of a detailed systemic evaluation with an elaborate cardiac assessment in children with SNHL, more so in the presence of frequent unexplained acute life-threatening episodes.

Polymerase Gamma Mitochondrial DNA Depletion Syndrome Initially Presenting as Disproportionate Respiratory Distress in a Moderately Premature Neonate: A Case Report

A 32-week premature infant presented with respiratory failure, later progressing to pulmonary hypertension (PH), liver failure, lactic acidosis, and encephalopathy. Using exome sequencing, this patient was diagnosed with a rare Polymerase Gamma (POLG)-related mitochondrial DNA (mtDNA) depletion syndrome. This case demonstrates that expanding the differential to uncommon diagnoses is important for complex infants, even in premature neonates whose condition may be explained partially by their gestational age (GA). It also shows that patients with complex neonatal diseases with significant family history may benefit from exome sequencing for diagnosis.

Effects of endothelins and matrix metalloproteinases in various pathological disorders and their antagonism at a better treatment modality in modern medicine

Chronic disorders or diseases like hypertension, diabetes-mellitus, cancer, heart failure, pulmonary hypertension are becoming more prevalent nowadays even at a younger age. Various methods have been introduced to determine several diseases out of which the concept of measurement of endothelins and matrix metalloproteinases and the usage of endothelin receptor antagonist as a way of treatment either singly or combinedly with other drugs has achieved more importance. By the usage of serum matrix metalloproteinases (MMPs) and endothelins we can determine the people who are at risk of developing hypertension, type2 diabetes, heart failure, atherosclerosis, cancer, pulmonary hypertension and can also assess the range of complications that are going to occur in the individual. These elevated levels cause remodelling after a period of time. Hence, the detection is done through a method in which few factors like endothelins and MMPs of our body are measured through a blood sample, maximum benefits can be obtained in individuals who have a significant family history of developing hypertension and other conditions In this review we have discussed about various effects of endothelins in different conditions, and also to know if these conditions can be improved or not by using endothelin receptor antagonists.

Myositis, rhabdomyolysis and severe hypercalcaemia in a body builder

Summary A 53-year-old man who used growth hormone (GH), anabolic steroids and testosterone (T) for over 20 years presented with severe constipation and hypercalcaemia. He had benign prostatic hyperplasia and renal stones but no significant family history. Investigations showed – (1) corrected calcium (reference range) 3.66 mmol/L (2.2–2.6), phosphate 1.39 mmol/L (0.80–1.50), and PTH 2 pmol/L (1.6–7.2); (2) urea 21.9 mmol/L (2.5–7.8), creatinine 319 mmol/L (58–110), eGFR 18 mL/min (>90), and urine analysis (protein 4+, glucose 4+, red cells 2+); (3) creatine kinase 7952 U/L (40–320), positive anti Jo-1, and Ro-52 antibodies; (4) vitamin D 46 nmol/L (30–50), vitamin D3 29 pmol/L (55–139), vitamin A 4.65 mmol/L (1.10–2.60), and normal protein electrophoresis; (5) normal CT thorax, abdomen and pelvis and MRI of muscles showed ‘inflammation’, myositis and calcification; (6) biopsy of thigh muscles showed active myositis, chronic myopathic changes and mineral deposition and of the kidneys showed positive CD3 and CD45, focal segmental glomerulosclerosis and hypercalcaemic tubular changes; and (7) echocardiography showed left ventricular hypertrophy (likely medications and myositis contributing), aortic stenosis and an ejection fraction of 44%, and MRI confirmed these with possible right coronary artery disease. Hypercalcaemia was possibly multifactorial – (1) calcium release following myositis, rhabdomyolysis and acute kidney injury; (2) possible primary hyperparathyroidism (a low but detectable PTH); and (3) hypervitaminosis A. He was hydrated and given pamidronate, mycophenolate and prednisolone. Following initial biochemical and clinical improvement, he had multiple subsequent admissions for hypercalcaemia and renal deterioration. He continued taking GH and T despite counselling but died suddenly of a myocardial infarction. Learning points: The differential diagnosis of hypercalcaemia is sometimes a challenge. Diagnosis may require multidisciplinary expertise and multiple and invasive investigations. There may be several disparate causes for hypercalcaemia, although one usually predominates. Maintaining ‘body image’ even with the use of harmful drugs may be an overpowering emotion despite counselling about their dangers.

Mesenteric Panniculitis in a Patient with Homozygous Factor V Leiden Gene Mutation: A Case and Literature to Review

A 30-year-old Asian male with a significant history of deep vein thrombosis and family history positive for pulmonary embolism presented with complaints of fever, nonradiating epigastric pain, and a sense of abdominal fullness. After the initial workup, ultrasonography of the whole abdomen was carried out which showed thrombus formation in the portal vein. A CT scan of the abdomen was performed, which showed findings suggestive of mesenteric panniculitis. Keeping the significant family history and imaging findings in mind, the clotting and thrombin profiles were analysed and came back positive for the factor V Leiden gene (homozygous). A CT angiogram was performed to demonstrate extensive thrombosis throughout the abdominal vasculature with cavernous transformation. It is asserted that the chronic thrombosis on a background of factor V mutation led towards chronic inflammation of the mesentery. To the authors’ knowledge it is the first reported case of mesenteric panniculitis in a patient with factor V homozygous gene mutation.

Urgent cancer genetic counseling and testing for young, premenopausal women with breast cancer (BC): Impact on surgical decision-making for contralateral risk-reducing mastectomy.

1533 Background: In women newly diagnosed with unilateral breast cancer (BC), contralateral risk-reducing mastectomy (CRRM) to decrease risk for additional primary BC is an appropriate option for some individuals, such as those with significantly increased risk due to a pathogenic variant (PV) in a breast cancer predisposition gene. Genetic testing at the time of BC diagnosis for young women has become more available and could aid in the decision-making process. We evaluated the trends for CRRM in a cohort of women diagnosed with BC at age ≤45 years who were seen in a multidisciplinary clinic where genetic counseling and testing is offered to each patient. Methods: A single institution, prospectively maintained database of patients seen in a BC multidisciplinary clinic between November 2014 and June 2019 was reviewed. Patients were included if they had non-metastatic, unilateral BC diagnosed ≤45 years of age, and underwent genetic testing at the time of BC diagnosis. Associations between surgical treatment (lumpectomy, mastectomy, or mastectomy with CRRM) and age at diagnosis, BC stage, family history, and genetic testing results were evaluated. Results: 184 patients were included in the analysis. The prevalence of a PV in a breast cancer predisposition gene was 15.8% (29/184; 1 in ATM, 12 in BRCA1, 8 in BRCA2, 5 in CH EK2, 2 in NBN, and 1 in NF1). 69% of the PV were in BRCA1 and BRCA2. 126 (68.4%) tested negative, and 29 (15.8%) had a variant of uncertain significance (VUS) in various genes. Overall, 63 patients (34.2%) elected to have CRRM. Of the 29 patients with a PV, 24 (82.8%) had CRRM. Women who chose CRRM were younger, more likely to test positive for a PV in a breast cancer predisposition gene, and more likely to have a significant family history of breast and/or ovarian cancer. Among the 155 patients who tested negative or had a VUS, there was no statistically significant association between CRRM and age (p = 0.58), test result (negative vs. VUS. p = 0.12), or family history (p = 0.32). Conclusions: For young women with BC seen in a multidisciplinary clinic, a younger age, significant family history, and positive genetic testing result were found to be associated with the decision to undergo CRRM. Among those without a genetic predisposition, having a VUS result was not associated with choosing CRRM. Incorporation of genetic services in the initial evaluation of young patients newly diagnosed with BC could add relevant information in surgical decision making and promote risk-appropriate management.