Reduced Tendon Reflexes Research Articles

Autoimmunity to voltage‐gated calcium channels

AbstractSeveral review articles on voltage‐gated calcium channels (VGCCs) classify VGCCs into five electrophysiological types and 10 genotypes. Each VGCC is distributed in different organs and specialized cells, and various organ‐specific human genetic diseases have been reported. Most of the human diseases caused by abnormalities in the VGCCs are genetic diseases. To the best of our knowledge, Lambert–Eaton myasthenic syndrome (LEMS) appears to be the only autoimmune disease for VGCCs. Approximately 90% of LEMS patients are positive for autoantibodies against P/Q‐VGCCs in the active zone of nerve endings. On the other hand, about 50% of LEMS patients a tumor‐associated neurological syndrome with small cell lung cancer. Neurological symptoms in LEMS patients include weakness of proximal limb muscles, reduced tendon reflexes, autonomic neuropathy, and in 9%–14% of patients, cerebellar ataxia, and paraneoplastic cerebellar degeneration. In the second half of this manuscript, we provide a clinical review with reference to the recently published Practical Guideline for Myasthenia gravis and LEMS 2022 in Japan.

Frequency Of Peripheral Neuropathy in Chronic Hepatitis C Patients Presenting at Liaquat University Hospital, Hyderabad

Hepatitis C virus (HCV) and its infective pathogenic role leads to the psychiatric and neurological signs and symptoms. Therefore, close monitoring and regular follow-up is warranted. Objective: To find out the frequency of peripheral neuropathy among patients presenting at Liaquat University Hospital, Hyderabad, having Chronic Hepatitis C. Methods: The cross-sectional study included 359 patients with chronic HCV, aged 20 to 70 years, who presented to the Liaquat University Hospital's Hepatitis Clinic and Outpatient Department of General Medicine and Neurology. Non-probability - sequential sampling was used to choose patients. Patients were asked about demographic information and the duration of chronic HCV after giving informed written consent. The clinical examination was performed to see if there were any reduced tendon reflexes in all of the patient's extremities. To diagnose peripheral neuropathy based on nerve conduction velocity, all patients had an electrophysiological test using a simplified nerve conduction study (NCS) methodology (NCV). The research lasted six months, from June 2021 to December 2021. The information was examined via SPSS version 25.0. Results: There were 219 Men (61%) And 140 Females (39%) among the 359 Patients. The average age (SD) of the participants was 42.3 (8.7) years (range 22–70). HCV infection lasted 36 months on average (range 1–156). Out of 359 patients, 61 had clinical peripheral neuropathy (PN) (17%). Electrophysiological evidence of PN was present in all of these patients, electrophysiological investigation revealed subclinical PN in 19 more patients (5.3%). Conclusion: On the basis of the findings from this study, it can be concluded that a high prevalence of peripheral neuropathy is present among the patients with HCV in our locality. However, an electrophysiological examination should always be done to avoid underestimating PN, particularly in older HCV patients.

Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family

BackgroundCa2+ as a universal second messenger regulates basic biological functions including cell cycle, cell proliferation, cell differentiation, and cell death. Lack of the protein mitochondrial calcium uptake1 (MICU1), which has been regarded as a gatekeeper of Ca ions, leads to the abnormal mitochondrial Ca2+ handling, excessive production of reactive oxygen species (ROS), and increased cell death. Mutations in MICU1 gene causes a very rare neuromuscular disease, myopathy with extrapyramidal signs (MPXPS), due to primary alterations in mitochondrial calcium signaling which demonstrates the key role of mitochondrial Ca2+ uptake. To date, 13 variants have been reported in MICU1 gene in 44 patients presented with the vast spectrum of symptoms.Case presentationHere, we report a 44-year-old Iranian patient presented with learning disability, muscle weakness, easy fatigability, reduced tendon reflexes, ataxia, gait disturbance, elevated hepatic transaminases, elevated serum creatine kinase (CK), and elevated lactate dehydrogenase (LDH). We identified a novel nonsense variant c.385C>T; p.(R129*) in MICU1 gene by whole exome sequencing (WES) and segregation analysis.ConclusionsOur finding along with previous studies provides more evidence on the clinical presentation of the disease caused by pathogenic mutations in MICU1. Finding more variants and expanding the spectrum of the disease increases the diagnostic rate of molecular testing in screening of this kind of diseases and in turn improves the quality of counseling for at risk couples and helps them to minimize the risks of having affected children.

Hemodiafiltration for Intoxication with Lithium Unmasking Its Anti-Parkinsonian Effect

From lithium it is known that it exhibits an anti-Parkinson effect [1]. Accordingly, smokers develop less frequently Parkinson’s Disease (PD) than the non-smoking population [2]. This is because tobacco contains a significant amount of lithium [3]. The anti-PD effect of lithium is explained by increased autophagy and reduction of intracellular a-synuclein [3]. Lithium inhibits GSK-3ß and consequently increases the ß-catenine activity [4]. Development of a Parkinson crisis due to flushing out of lithium by Hemodiafiltration (HDF), as in the following case, has not been reported. The patient is a 63 years male (height 180cm, weight 75kg) who was living with his mother in a retirement home and developed fever since 4 days prior to admission. His previous history was positive for psychosis, bipolar disorder, arterial hypertension, chronic renal failure, chronic obstructive pulmonary disease, diabetes, bilateral hydrocele, prostate hypertrophy, polyneuropathy, lithium intoxication, and hyperlipidemia. He had the diagnosis of a questionable extra-pyramidal syndrome but no anti-Parkinson medication. His home medication included aripiprazole (400 mg/ once every 30 d), biperiden (8 mg/d), midazolam (0.25 mg/d), lithium (900 mg/d), quetiapine (50 mg/d), trazodone (75 mg/d), nebivolol (2.5 mg/d), metformin (850 mg/d), simvastatin (20 mg/d), tamsulosin (0.4 mg/d), fenoterol with ipratropium-bromid, and tiotropium plus olodaterol. On admission (hospital day-1 (hd1)) he was comatose, had spontaneous resting tremor, and arterial hypotension (80/40 mmHg). Blood tests revealed hypokaliemia, hypernatriemia, and renal insufficiency (Table 1). The swab test for SARS-CoV2 was negative. ECG showed AV-block-I, right bundle-branch-block, and QT-prolongation (501 ms). X-ray of the lung was normal. Clinical neurologic exam on hd2 revealed somnolence, pain upon maximal passive anteflexion of head, nuchal rigor, ptosis, ophthalmoparesis, spontaneous myocloni all over the body, mild rigor of all extremities, reduced tendon reflexes on the lower limbs, and clonus of the left lower leg (Table 1). Cerebral CT-scan was non-informative. He was treated with fluid substitution, cefuroxim, levetirazetam (LEV) (1000 mg/d), and discontinuation of all psychiatric medication.

Stroke-like lesions in mitochondrial disease may resemble ischemic stroke

The patient is a 73-y-male who was referred after a fall without losing consciousness or secessus. Clinical exam revealed disorientation, ophthalmoparesis, hemianopia to the left, left hemineglect, hypoacusis, quadruparesis, general wasting, generally reduced tendon reflexes, mild rigor, occasional myoclonic jerks of the right lower limb, and ataxia of the left lower limb. Cerebral magnetic resonance imaging (MRI) showed a stroke-like lesion (SLL), generalized atrophy, white matter lesions, and ponsgliosis. The previous history was positive for diabetes, hypoacusis, arterial hypertension, hyperlipidemia, vitamin-D deficiency, cataract, esophageal adenocarcinoma, histiocytoma, Barrett esophagus, hiatal hernia, colonic polyps, and lactic acidosis. Based upon this phenotypic spectrum, lactic acidosis, and the cerebral MRI, a mitochondrial disorder (MID) was diagnosed. This case shows that a MID may be missed for years, that an SLL may be easily mixed up with ischemic stroke; and that the initial manifestation of an SLL may be a fall.

Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy

Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.

A rare form of metabolic myopathy in a neurologist’s practice

Secondary metabolic myopathies develop in endocrine pathologies, different somatic diseases, electrolyte disorders and in some vitamin deficiency. Myopathic syndrome caused by vitamin D deficit is a rear pathologic condition, for this reason it is difficult to diagnose it. Proper diagnosis has a vital importance for proper treatment choice. The article describes a rear form of the metabolic myopathy in a young female admitted to the neurology department because of significant leg weakness. A thorough examination revealed no pathology of internal organs. On physical examination moderate lower flaccid paresis with reduced tendon reflexes was revealed. Muscle tone was normal. The absence of systemic inflammatory changes in blood tests as well as normal biopsy results ruled out dermatomyositis and polymyositis. Blood tests revealed deficiency of 25-OH-vitamin D. On vitamin D monotherapy leg weakness completely resolved. In case of myopathic syndrome it is necessary to have in mind such rear causes for its development as vitamin D deficiency.

Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene

Severe cardiomyopathy in a young patient with complete deficiency of adipose triglyceride lipase due to a novel mutation in PNPLA2 gene

Exhaustion or fatigability may not only be cardiac but also myopathic.

To the Editor, With interest, we read the article by Yaksh et al. about a patient with left ventricular hypertrabeculation/noncompaction and Wolff–Parkinson–White syndrome who also manifested with ventricular tachycardia. We have the following comments and concerns. The patient described is not the first adult with noncompaction who also presented with Wolff–Parkinson–White syndrome. In a previous report, one of the two noncompaction patients from the same family had pre-excitation on electrocardiography [1]. The combination of noncompaction and pre-excitation was also reported in two adult Chinese patients [2]. Additionally, Wolff–Parkinson–White syndrome was described by Moceri et al. and Brembilla-Perrot et al. in a single patient each [3, 4]. In a study of 86 noncompaction patients, Wolff–Parkinson–White syndrome was found in two of them [5]. The authors mention that noncompaction was first described by Engberding et al. [6]. Engberding et al. were indeed the first to recognize and describe this unclassified cardiomyopathy on echocardiography, but there are indications that noncompaction had been described earlier, as indicated in the paper by Feldt et al. in 1969 [7]. Noncompaction is not only associated with electrocardiographic abnormalities such as right bundle branch block, supraventricular tachycardia, or ventricular tachycardia, but any type of electrocardiographic abnormality may be observed in these patients including atrial fibrillation, atrioventricular block, left bundle branch block, or QT prolongation [5]. Easy fatigability or exhaustion may not only be a cardiac symptom but may also be a clinical manifestation of a neuromuscular disorder, frequently associated with noncompaction [8]. Was the patient investigated for neuromuscular disorders by a neurologist? Did she present with any other feature of a neuromuscular disorder, such as muscle weakness, wasting, reduced tendon reflexes, muscle aching, muscle cramping, double vision, or ptosis? Not only symptomatic patients are investigated for noncompaction but also asymptomatic patients, as reported in a number of cases and family studies. Occasionally noncompaction is found in asymptomatic relatives of symptomatic noncompaction cases. In a family study of 25 relatives of noncompaction patients, asymptomatic noncompaction was detected in four of these relatives [9]. Surprisingly, the authors mention in the discussion that atrial fibrillation could have been the cause of ventricular tachycardia in their patient [6]. Did the patient receive oral anticoagulation in addition to ablation and implantable cardioverter defibrillator implantation as a prophylactic measure? It is essential to put noncompaction patients on oral anticoagulation as soon as atrial fibrillation or heart failure has been documented. How often did the implantable cardioverter defibrillator discharge during follow-up and which was the arrhythmia that caused the implantable cardioverter defibrillator to react? In the introduction the authors mention that the clinical presentation of noncompaction includes heart failure, thromboembolic events, or arrhythmias [6]. However, noncompaction patients may present with other cardiac manifestations, particularly if noncompaction is associated with functional or morphological abnormalities in addition to noncompaction (non-isolated noncompaction) [10]. Overall, there is a need to thoroughly investigate and describe noncompaction patients, to screen noncompaction patients for neuromuscular disorders or chromosomal abnormalities, and to screen other family members for noncompaction. For clarification of the pathogenetic background of noncompaction, it is useful to search for any genetic abnormality that may explain the occurrence of noncompaction.

Dysuria, Urinary Retention, and Inguinal Pain as Manifestation of Sacral Bannwarth Syndrome.

Only few cases with sacral radiculitis due to infection with Borrelia burgdorferi leading to neurogenic urinary dysfunction have been reported. A 57-year-old male developed urethral pain and urinary retention, requiring permanent catheterization. Extensive urological investigations did not reveal a specific cause, which was why neurogenic bladder dysfunction was suspected. Neurologic exam revealed only mildly reduced tendon reflexes. Cerebral and spinal MRI were noninformative. CSF investigations, however, revealed pleocytosis, elevated protein, and antibodies against Borrelia burgdorferi. Intravenous ceftriaxone for three weeks resulted in immediate improvement of bladder dysfunction, with continuous decline of residual urine volume and continuous increase of spontaneous urine volume even after removal of the catheter and initiation of self-catheterization. Sacral radiculitis due to infection with Borrelia burgdorferi is a potential cause of detrusor areflexia and urethral, perineal, inguinal, and scrotal pain and may be misinterpreted as cystitis or urethritis. Ceftriaxone may result in progressive recovery of bladder dysfunction and pain. Neuroborreliosis may manifest exclusively as neurourological problem.

Hereditary Neuropathy with Liability to Pressure Palsies Masked by Previous Gunshots and Tuberculosis

Objectives. Although hereditary neuropathy with liability to pressure palsies (HNPP) presents with a distinct phenotype on history, clinical exam, and nerve conduction studies, it may be masked if diagnostic work-up suggests other causes. Case Report. In a 37-year-old male with pseudoradicular lumbar pain, neurological exam revealed sore neck muscles, peripheral facial nerve palsy, right anacusis and left hypoacusis, hemihypesthesia of the right face, mild distal quadriparesis, diffuse wasting, and generally reduced tendon reflexes. He had a history of skull fracture due to a gunshot behind the right ear and tuberculosis for which he had received adequate treatment for 3 years; MRI revealed a disc prolapse at C6/7 and Th11/12. Nerve conduction studies were indicative of demyelinating polyneuropathy with conduction blocks. Despite elevated antinuclear antibodies and elevated CSF-protein, HNPP was diagnosed genetically after having excluded vasculitis, CIDP, radiculopathy, and the side effects of antituberculous treatment. Conclusions. HNPP may manifest with mild, painless, distal quadriparesis. The diagnosis of HNPP may be blurred by a history of tuberculosis, tuberculostatic treatment, hepatitis, and the presence of elevated CSF-protein.

65. Peripheral nerve ultrasonography: Clinical use

Charcot–Marie–Tooth disease (CMT) is an heterogeneous group of hereditary neuropathies characterized by weakness and atrophy of the limbs, loss of sensation and absent or reduced tendon reflexes. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) causes progressive or recurrent weakness and numbness of the limbs. Both CMT and CIDP share similar nerve conduction study abnormalities (reduced amplitude of sensory and motor potentials, and reduced conduction velocity). The aim of our study was to compare the ultrasound (US) data recorded in genetic neuropathy (CMT) and inflammatory neuropathy (CIDP). We enrolled 10 patients with CMT type 1A and 10 patients with CIDP. In this study we compared left and right median nerve cross-sectional area (CSA) and echogenicity nerve in the forearm, between two groups of patients to evaluate a possible difference. Three US classes were identified based on CSA and echogenicity. For all patient included neurophysiological assessment was used to estimate a possible correlation between the nerve conduction study variables and US data. US of the nerve can be a tool of significant value in the differential diagnosis in different neuropathies.

G.O.3: Severe congenital actin related myofibrillar myopathy

Mutations in ACTA1 have been associated with nemaline myopathy, intranuclear rod myopathy, actin myopathy, cap myopathy, and congenital fiber type disproportion. Myofibrillar myopathies (MFM) are morphologically distinct but genetically heterogeneous muscular dystrophies arising from mutations in Z-disk related proteins. A 26-month-old boy was hypotonic and weak at birth, had significantly delayed motor development, and was mechanically ventilated and tube-fed since birth. At age 26 months he had cup-shaped low-set ears, a high-arched palate, contractures of the metacarpophalangeal and proximal interphalangeal joints, and facial diplegia with diffuse muscle weakness and reduced tendon reflexes, but had good head control and could sit with support. The EMG showed prominent fibrillation potentials and myopathic motor unit potentials. The muscle biopsy revealed abnormal variation in fiber size, fiber splitting, increased internal nuclei, vacuolar change, myofibrillar disorganization, hyaline structures, focal decreases of oxidative enzyme activity as well as scattered necrotic and regenerating fibers with marked increase of endomysial and perimysial connective tissue. Many structurally abnormal fibers displayed ectopic or abnormal expression of desmin, alphaB-crystallin, myotilin, dystrophin, and NCAM. Whole exome sequencing demonstrated a previously published in-frame insertion of two amino acids in ACTA1 . The mutant actin was expressed at ∼11% of wild-type in COS7 and C2 cells. C2 cells expressing mutant actin displayed cytoplasmic actin aggregates of different sizes whereas cells expressing wild-type actin displayed mostly filamentous actin. We conclude that (1) mutations in ACTA1 can cause MFM pathology; (2) MFM can be present at birth; (3) mutations in ACTA1 should be considered in patients with severe congenital hypotonia associated with muscle weakness and MFM pathology.

Wearable Cardioverter-Defibrillator in a Patient with Left Ventricular Noncompaction/Hypertrabeculation, Coronary Artery Disease, and Polyneuropathy

A 55-year-old Caucasian male with coronary heart disease was admitted because of dyspnea for 4 weeks. Echocardiography showed a dilated left ventricle with an ejection fraction of 34% and apical left ventricular hypertrabeculation/noncompaction with an apical thrombus. Neurologic examination revealed positional tremor and generally reduced tendon reflexes. During 8 weeks, his condition improved under pharmacotherapy. The patient was skeptical about implantable cardioverter-defibrillator (ICD) and expected further improvement from pharmacotherapy. Thus, he received a wearable cardioverter-defibrillator (WCD). We conclude that a WCD might be useful in noncompaction patients in whom improvement of systolic dysfunction is expected or who are skeptical about ICDs.

Letter to the Editor Complex-I defect with minimal manifestations

Letter to the Editor Complex-I defect with minimal manifestations

Epilepsy and noncompaction

Dear Sir, With interest we read the article by Dello et al. about a patient with left ventricular hypertrabeculation/noncompaction (LVHT) and syncope being attributed to ventricular tachycardia [1]. We have the following comments and concerns. Work-up for syncope not only requires cardiological but also neurological investigations. It is important not only to rule out epilepsy but also ischaemic stroke or cerebral bleeding. In this respect it is important to carry out multimodal cerebral MRI to receive not only parenchymatous but also vascular information. Stroke is particularly prevalent in LVHT patients because of embolism from thrombus formation within the intertrabecular spaces [2]. Single patients with LVHT may also develop atrial fibrillation, the most common risk factor for embolic stroke. A number of patients with LVHT also develop systolic dysfunction, another risk factor for stroke or embolism [3]. Did the described patient undergo cerebral MRI and what was the result? Where any old ischaemic lesions seen on TIRM sequences? Syncope may also derive from stenosis of the extra-cranial cerebral arteries. Did the patient undergo carotid ultrasound or contrast-enhanced MR angiography to rule out high-grade stenosis of the internal carotid arteries or dissection of the carotid or vertebral arteries? A further neurological cause of syncope may be affection of the peripheral nerves [4]. Were there any indications for vegetative polyneuropathy in the described patient? Did he present with weakness, wasting, reduced tendon reflexes, or sensory disturbances? Was the patient seen by a neurologist to rule out or confirm acute or chronic polyneuropathy? A fourth reason why the neurologist should see LVHT patients is the frequent association of LVHT with neuromuscular disorders [5]. Particularly muscle disease is highly prevalent among LVHT patients, although a causative relation between neuromuscular disorders and LVHT has not been proven yet. It would be also interesting to receive a more detailed description of the paroxysmal activity on EEG? How often did the patient experience seizures? What type of seizures did he experience? Only focal or also generalised seizures? Did he also present with non-convulsive seizures? When was the onset of epilepsy, what was the seizure frequency, what were the most frequent triggers for seizures in this particular patient? Did he have a family history positive for epilepsy, did he have a history of birth trauma, cerebral hypoxia, fever cramps, traumatic brain injury, meningitis, or a history of neurosurgery? What was the cause of epilepsy and did he ever take antiepileptic drugs other than levetiracetam? How do the authors know that paroxysmal activity on EEG was secondary to arrhythmias and not primary due to a double trouble? It is not unusual that EEG is normal after a seizure, particularly after initiation of antiepileptic treatment. EEGs may be also abnormal in patients without epilepsy, such as in patients with migraine or other types of headache. Did the patient report a history of headache? Did he experience further seizures after discharge? How frequently did he attend the follow-ups? How were the follow-up EEGs? Was the family history positive for epilepsy? Overall, there is a strong need to investigate LVHT patients with a history of syncope or epilepsy more thoroughly, particularly by referral to the neurologist. The neurologist must rule out stroke, epilepsy, carotid artery stenosis, polyneuropathy, or myopathy. Seizures in LVHT patients may not only be due to ischaemia during ventricular arrhythmias but also an independent second trouble in these patients.

Molecular basis of Charcot–Marie–Tooth type 2B disease

CMT2B (Charcot-Marie-Tooth type 2B) disease is an autosomal dominant peripheral neuropathy whose onset is in the second or third decade of life, thus in adolescence or young adulthood. CMT2B is clinically characterized by severe symmetric distal sensory loss, reduced tendon reflexes at ankles, weakness in the lower limbs and muscle atrophy, complicated by ulcerations that often lead to amputations. Four missense mutations in the gene encoding the small GTPase Rab7 cause the CMT2B neuropathy. Rab7 is a ubiquitous protein that regulates transport to late endosomes and lysosomes in the endocytic pathway. In neurons, Rab7 is important for endosomal trafficking and signalling of neurotrophins, and for retrograde axonal transport. Recent data on CMT2B-causing Rab7 mutant proteins show that these proteins exhibit altered koff rates and, as a consequence, they are mainly in the GTP-bound state and bind more strongly to Rab7 effector proteins. Notably, expression of CMT2B-causing Rab7 mutant proteins strongly inhibit neurite outgrowth in several cells lines and alter NGF (nerve growth factor) trafficking and signalling. These data indicate that Rab7 plays an essential role in neuronal cells and that CMT2B-causing Rab7 mutant proteins alter neuronal specific pathways, but do not fully explain why only peripheral neurons are affected in CMT2B. In the present paper, we discuss the current understanding of the molecular and cellular mechanisms underlying CMT2B, and we consider possible hypotheses in order to explain how alterations of Rab7 function lead to CMT2B.

MiR-886-3p Levels Are Elevated in Friedreich Ataxia

Friedreich ataxia (FRDA) is the most common inherited ataxia caused primarily by an intronic GAA.TTC triplet repeat expansion in the frataxin (FXN) gene. FXN RNA and protein levels are reduced in patients leading to progressive gait and limb ataxia, sensory loss, reduced tendon reflexes, dysarthria, absent lower limb reflexes, and loss of position and vibration sense. Neurological manifestations ensue from primary loss of dorsal root ganglia neurons and their associated axons ascending centrally in the spinal cord and peripherally in large myelinated nerves. Small noncoding RNAs such as microRNAs have been shown to be dysregulated in neurodegenerative diseases such as Alzheimer's and Huntington's disease. Here we report that hsa-miR-886-3p (miR-886-3p) was increased in patient cells as well as peripheral patient blood samples. Selective reduction in miR-886-3p by an anti-miR led to elevation of FXN message and protein levels without associated changes in histone marks at the FXN locus. Nevertheless, derepression of frataxin by a histone deacetylase inhibitor leads to a decrease in miR-886-3p. These results outline involvement of a small RNA, miR-886-3p in FRDA and a novel therapeutic approach to this disease using an anti-miR-886-3p.

Novel c.367_369del LMNA mutation manifesting as severe arrhythmias, dilated cardiomyopathy, and myopathy

ObjectiveThe 3-bp deletion in exon 2 of the Lamin A/C (LMNA) gene has not been described in association with dilated cardiomyopathy, which is characterized by progressive heart failure, atrioventricular (AV) block, tachyarrhythmias, and variable skeletal muscle involvement. Case ReportIn a 43-year-old woman with a long-term history of palpitations and newly diagnosed AV blocks I and II, ventricular ectopic beats, inducible nonsustained ventricular tachycardias (VTs), cardiac arrest, and successful resuscitation, an implantable cardioverter defibrillator was successfully implanted. Her family history was positive for sudden cardiac death (her father and sister), dyspnea and heart failure (her grandmother and sister), palpitations (her brother), and elevated levels of creatine-kinase (CK) (her sister). Two cousins had died of nonspecific muscular dystrophy at ages 10 years and 11 years. Upon neurological investigations revealing sore neck muscles, reduced tendon reflexes, and detached, spot-like white matter lesions bilaterally, a neuromuscular disorder was suspected. The direct sequencing of all exons and flanking intronic regions of the LMNA gene detected the heterozygote 3-bp deletion (AAG) c.367_369del in exon 2 of the gene. This mutation resulted in the deletion of a lysine at position 123 (p.lys123del) in the lamin A/C protein. ConclusionsThe novel 3-bp deletion in exon 2 of the LMNA gene may phenotypically manifest as dilated cardiomyopathy, heart failure, severe tachyarrhythmias, and muscular dystrophy. Sudden cardiac death from ventricular fibrillation may be prevented in LMNA mutation carriers if the diagnosis is established early enough to implant a cardioverter defibrillator.

Central and peripheral autonomic failure in cold-induced sweating syndrome type 1

Cold-induced sweating syndrome type 1 (CISS1) is a rare disorder characterized by profuse sweating in a cold environment, determined by mutations in cytokine receptor–like factor 1 ( CRLF1 ).1 Its pathogenesis is not fully understood. It has been demonstrated in vitro that CRLF1 may be involved in inducing differentiation from a noradrenergic to a cholinergic transmitter phenotype. During development, catecholaminergic and cholinergic neurotransmission is required for the induction of secretory function, whereas cholinergic transmission becomes crucial for the maintenance of the secretory responsiveness.2 The abnormal sweat response in CISS1 could be also related to alterations in temperature signals acting on hypothalamus and preoptic areas.1 We report clinical, molecular, skin biopsy, and temperature monitoring data of an Italian boy with CISS1. ### Case report. A 16-year-old boy had come to our observation at 1 year of age. His parents were healthy and unrelated. A brother, with facial dysmorphisms and hypotonia, had died at age 3 months from bronchopulmonary infection. Our patient was hypotonic at birth and experienced severe feeding difficulties. He had elongated face, high-arched palate, weak cry, large pinnae, short hands, tapering fingers, clinodactyly, and reduced tendon reflexes. Concentric needle EMG, nerve conduction velocity (NCV) studies (ulnar, median, peroneal, tibial, and sural nerves), and repetitive nerve stimulation testing excluded a …