-
BMC Medical Genomics Jun 2024TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and...
BACKGROUND
TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants.
METHODS
Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed.
RESULTS
TTN c.38,876-2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases.
CONCLUSIONS
Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.
Topics: Humans; Female; Connectin; Pedigree; Male; Exome Sequencing; Arthrogryposis; Contracture; Mutation; Pregnancy; Fetus; Adult
PubMed: 38937733
DOI: 10.1186/s12920-024-01946-z -
World Journal of Clinical Cases Oct 2023Takotsubo cardiomyopathy, also called apical ballooning syndrome, is a disease that is often triggered by stress factors in postmenopausal women and mimics acute...
BACKGROUND
Takotsubo cardiomyopathy, also called apical ballooning syndrome, is a disease that is often triggered by stress factors in postmenopausal women and mimics acute coronary syndrome. The aim of this article is to draw attention to takotsubo cardiomyopathy after surgical treatment of liver hydatid cyst.
CASE SUMMARY
A 50-year-old diabetic and hypertensive female patient was evaluated preoperatively before general surgery for liver hydatid cyst, and no cardiac problems were found. The patient was discharged on the 3 postoperative day without any postoperative complications. On postoperative day 5, the patient presented to the emergency department with fever, shortness of breath, chills, and shivering and was hospitalized with the diagnosis of pneumonia. The troponin levels remained high during follow-up. Echocardiography was performed on postoperative day 7, after which the patient was referred to a tertiary center with the diagnosis of non-ST-elevation myocardial infarction due to akinesia in the apical region. Coronary angiography performed at the tertiary center showed normal coronary anatomy, and the patient was diagnosed with takotsubo cardiomyopathy.
CONCLUSION
Takotsubo cardiomyopathy mimicking myocardial infarction without ST segment elevation may develop after surgical treatment of liver hydatid cyst.
PubMed: 37946773
DOI: 10.12998/wjcc.v11.i29.7187 -
Prenatal Diagnosis Apr 2024Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present...
Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.
Topics: Female; Humans; Pregnancy; Abnormalities, Multiple; Cleft Palate; Lymphangioma, Cystic; Malignant Hyperthermia; Muscular Diseases; Ryanodine Receptor Calcium Release Channel; Skin Abnormalities; Fetal Diseases
PubMed: 38520674
DOI: 10.1002/pd.6553 -
Clinical Parkinsonism & Related... 2024Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture....
Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.
PubMed: 38845753
DOI: 10.1016/j.prdoa.2024.100258 -
Clinical Genetics Feb 2024We report the third case of FADS due to biallelic DOK7 variants, which further strengthens the association of DOK7 with this lethal phenotype and lack of genotype... (Review)
Review
We report the third case of FADS due to biallelic DOK7 variants, which further strengthens the association of DOK7 with this lethal phenotype and lack of genotype phenotype correlation.
Topics: Humans; Arthrogryposis; Phenotype; Muscle Proteins
PubMed: 37849383
DOI: 10.1111/cge.14431 -
Neurobiology of Disease Aug 2024Parkinson's disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal...
Parkinson's disease is caused by a selective vulnerability and cell loss of dopaminergic neurons of the Substantia Nigra pars compacta and, consequently, striatal dopamine depletion. In Parkinson's disease therapy, dopamine loss is counteracted by the administration of L-DOPA, which is initially effective in ameliorating motor symptoms, but over time leads to a burdening side effect of uncontrollable jerky movements, termed L-DOPA-induced dyskinesia. To date, no efficient treatment for dyskinesia exists. The dopaminergic and serotonergic systems are intrinsically linked, and in recent years, a role has been established for pre-synaptic 5-HT1a/b receptors in L-DOPA-induced dyskinesia. We hypothesized that post-synaptic serotonin receptors may have a role and investigated the effect of modulation of 5-HT4 receptor on motor symptoms and L-DOPA-induced dyskinesia in the unilateral 6-OHDA mouse model of Parkinson's disease. Administration of RS 67333, a 5-HT4 receptor partial agonist, reduces L-DOPA-induced dyskinesia without altering L-DOPA's pro-kinetic effect. In the dorsolateral striatum, we find 5-HT4 receptor to be predominantly expressed in D2R-containing medium spiny neurons, and its expression is altered by dopamine depletion and L-DOPA treatment. We further show that 5-HT4 receptor agonism not only reduces L-DOPA-induced dyskinesia, but also enhances the activation of the cAMP-PKA pathway in striatopallidal medium spiny neurons. Taken together, our findings suggest that agonism of the post-synaptic serotonin receptor 5-HT4 may be a novel therapeutic approach to reduce L-DOPA-induced dyskinesia.
Topics: Animals; Dyskinesia, Drug-Induced; Levodopa; Oxidopamine; Mice; Male; Mice, Inbred C57BL; Serotonin 5-HT4 Receptor Agonists; Antiparkinson Agents; Corpus Striatum; Receptors, Serotonin, 5-HT4; Parkinsonian Disorders; Pyridines; Neurons; Piperidines; Pyrimidines
PubMed: 38852753
DOI: 10.1016/j.nbd.2024.106559 -
Journal of the Academy of... 2024Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with...
BACKGROUND
Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis.
METHODS
This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.
RESULTS
A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics.
CONCLUSIONS
Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.
Topics: Humans; Neuroleptic Malignant Syndrome; Case-Control Studies; Female; Male; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Adult; Antipsychotic Agents; Middle Aged; Young Adult; Mexico
PubMed: 38151160
DOI: 10.1016/j.jaclp.2023.12.002 -
American Journal of Medical Genetics.... Mar 2024ATP1A2 encodes a subunit of sodium/potassium-transporting adenosine triphosphatase (Na /K -ATPase). Heterozygous pathogenic variants of ATP1A2 cause familial hemiplegic...
ATP1A2 encodes a subunit of sodium/potassium-transporting adenosine triphosphatase (Na /K -ATPase). Heterozygous pathogenic variants of ATP1A2 cause familial hemiplegic migraine, alternating hemiplegia of childhood, and developmental and epileptic encephalopathy. Biallelic loss-of-function variants in ATP1A2 lead to fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, resulting in fetal death. Here, we describe a patient with compound heterozygous ATP1A2 variants consisting of missense and nonsense variants. He survived after birth with brain malformations and the fetal akinesia/hypokinesia sequence. We report a novel type of compound heterozygous variant that might extend the disease spectrum of ATP1A2.
Topics: Male; Humans; Hypokinesia; Sodium-Potassium-Exchanging ATPase; Microcephaly; Hemiplegia; Migraine with Aura; Syndrome
PubMed: 37870493
DOI: 10.1002/ajmg.a.63453 -
Kardiologiia Mar 2024To compare capabilities for diagnosing regional and global myocardial dysfunction using the values of longitudinal and circular strain, left ventricular (LV) torsion and...
Limitations of Diagnosis of Ischemic Left Ventricular Dysfunction Using the Values of Strain, Twist and Untwist in Patients With Myocardial Infarction of Various Localization.
AIM
To compare capabilities for diagnosing regional and global myocardial dysfunction using the values of longitudinal and circular strain, left ventricular (LV) torsion and untwisting in patients with myocardial infarction (MI) of various locations.
MATERIAL AND METHODS
Patients included in the study (n=121) were divided into three groups: patients with unstable angina (n=30), patients with anterior MI (n=45), and patients with inferior MI (n=46). Clinical, laboratory and instrumental test were performed, including echocardiography. For a quantitative analysis of LV contractility, the maximum systolic peaks of regional and global longitudinal and circular strain, systolic and diastolic rotation, LV torsion and untwisting were measured.
RESULTS
Anterior MI was characterized by injury of the LV apical segments, while inferior MI was characterized by injury of the basal segments. In anterior MI, the longitudinal strain was reduced less than 14.5% and circular strain less than 19.3% in the apical segment of the LV anteroseptal wall (ASW). In akinesia of the LV ASW apical segment, longitudinal and circular strains were reduced less than 10%. The magnitude of the circular strain of the LV ASW apical segment (diagnostic threshold 19.3%, sensitivity (Se) 87%, specificity (Sp) 90%) was superior to that of the longitudinal strain as a diagnostic marker for regional ischemic dysfunction in anterior MI. The magnitude of the circular strain of the basal segment of the LV inferior wall in inferior MI has a greater diagnostic value for identifying regional systolic dysfunction than the value of the longitudinal strain of this LV segment. The diagnostic threshold was 17.3%, Se 79%, Sp 80%.
CONCLUSION
A decrease in the circular strain of the LV ASW less than 19.3% in the LV apical segment is more specific (Sp 90%) for diagnosing regional systolic dysfunction in anterior MI than a decrease in longitudinal strain. A circular strain value of less than 17.3% in the basal segment of the LV inferior wall is more specific (Sp 80%) than the longitudinal strain of this segment for diagnosing regional systolic dysfunction in inferior MI. Predominant injury to the LV apex in anterior MI can cause systolic and diastolic myocardial dysfunction, which is manifested by a decrease in LV circular deformation, torsion and untwisting.
Topics: Humans; Myocardial Infarction; Myocardium; Angina, Unstable; Diastole; Ventricular Dysfunction, Left
PubMed: 38597763
DOI: 10.18087/cardio.2024.3.n2253 -
PCN Reports : Psychiatry and Clinical... Jun 2024Delayed neuropsychiatric sequelae (DNS) is a syndrome that appears days to weeks after acute carbon monoxide (CO) poisoning. DNS shows various neuropsychiatric symptoms,...
BACKGROUND
Delayed neuropsychiatric sequelae (DNS) is a syndrome that appears days to weeks after acute carbon monoxide (CO) poisoning. DNS shows various neuropsychiatric symptoms, such as mental deterioration and parkinsonism.
CASE PRESENTATION
Our case was a 37-year-old male with schizophrenia. He attempted suicide by CO poisoning and was brought to our emergency department (Day 0). He was ventilated with normobaric oxygen therapy for 3 days and moved to the psychiatric ward with clear consciousness. We restarted antipsychotics, and he gradually presented akinesia and rigidity. Additionally, around Day 32, he showed disorganized behaviors, mental deterioration, incontinence, and gait disturbance. Brain magnetic resonance imaging (MRI) showed slightly abnormal findings on Day 35. Although we suspected DNS on the clinical course and the MRI findings, catatonia and side-effects of antipsychotics were also considered. Finally, electroencephalography (EEG) on Day 38 with apparent abnormalities, including diffuse slow waves, resulted in our diagnosis of DNS, and he underwent hyperbaric oxygen therapy. His condition was dramatically improved, and his diffuse slow waves on EEG disappeared on Day 83. We also followed his clinical presentations and brain MRI until 33 months. Throughout the whole follow-up, his cognition, movement, and psychiatric symptoms remained stable. However, his brain MRI showed progressive atrophy in bilateral frontal lobes and increasing white matter lesions throughout the whole course.
CONCLUSION
EEG, as well as brain MRI, may be crucial in the differential diagnosis of DNS in patients with complex conditions involving medications and severe mental illnesses.
PubMed: 38910909
DOI: 10.1002/pcn5.218