scholarly journals Noonan Syndrome with Multiple Lentigines and PTPN11 Mutation: A Case with Intracerebral Hemorrhage

2021 ◽  
pp. 1-7
Author(s):  
Eduardo Orrego-González ◽  
Carlos Martin-Restrepo ◽  
Alberto Velez-Van-Meerbeke
Keyword(s):  
Intracerebral Hemorrhage ◽  
Noonan Syndrome ◽  
Tyrosine Phosphatase ◽  
Acute Onset ◽  
Physical Exam ◽  
Autosomal Dominant Disorder ◽  
Acute Hemorrhage ◽  
First Case ◽  
The Right ◽  
Multiple Lentigines

Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome, is a rare autosomal dominant disorder with an unknown prevalence. Characteristics of this disease include cutaneous, neurologic, and cardiologic abnormalities. In this case report, we present a 12-year-old girl who was admitted to the emergency department for acute-onset left weakness, unsteady gait, nausea, and vomiting. Her physical exam notably showed left side upper motor neuron signs and dysmetria. CT scan revealed an acute hemorrhage of the right thalamus. Physical exam exhibited several craniofacial dysmorphisms and lentigines. The genetic test revealed a heterozygous missense mutation in the protein tyrosine phosphatase non-receptor type 11 (<i>PTPN11</i>) gene and a variant of unknown significance of the <i>MYH11</i> gene. To the best of our knowledge, this is the first case of a patient with NSML presenting an intracerebral hemorrhage.

scholarly journals Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines

2015 ◽  
Vol 308 (9) ◽  
pp. H1086-H1095 ◽  
Author(s):  
Sarah A. Clay ◽  
Timothy L. Domeier ◽  
Laurin M. Hanft ◽  
Kerry S. McDonald ◽  
Maike Krenz
Keyword(s):  
Noonan Syndrome ◽  
Tyrosine Phosphatase ◽  
Severe Form ◽  
Cellular Mechanisms ◽  
Specific Expression ◽  
Plasmic Reticulum ◽  
Power Load ◽  
Intracellular Ca ◽  
Generating Capacity ◽  
Multiple Lentigines

Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca2+ homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4–6 wk of age. To assess Ca2+ handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca2+ transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca2+ content concurrent with increased expression of sarco(endo)plasmic reticulum Ca2+-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relationships and power-load curves were shifted upward. The peak power-generating capacity was increased approximately twofold. Transmission electron microscopy revealed that the relative intracellular area occupied by sarcomeres was increased in Q510E-SHP2 cardiomyocytes. Triton X-100-based myofiber purification showed that Q510E-SHP2 increased the amount of sarcomeric proteins assembled into myofibers. In summary, Q510E-SHP2 expression leads to enhanced contractile performance early in disease progression by augmenting intracellular Ca2+ cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM.

scholarly journals Idiopathic Omental Infarction Mimic Acute Appendicitis: A Case Report

2020 ◽  
pp. 1-3
Author(s):  
Hamad Almakinzy ◽  
Bandar Idress ◽  
Hamad Almakinzy
Keyword(s):  
Case Report ◽  
Acute Appendicitis ◽  
Acute Abdomen ◽  
Inflammatory Markers ◽  
Iliac Fossa ◽  
Young Patients ◽  
Acute Onset ◽  
First Case ◽  
Laparoscopy Surgery ◽  
The Right

Idiopathic Omental Infarct (IOI) is a rare cause of an acute abdomen that arises from an interruption of blood supply to the omentum. Since first case was described by Elitelin 1899, more than 300 cases have been published [1]. It can mimic serious surgical pathology. It occurs in <1% of appendicitis cases [2]. It’s challenge to diagnose, as features may mimic acute appendicitis and therefore in young patients, may only be discovered intra-operative. Here, we present a case of omental infarct in 26-year-old gentleman with no significant medical or surgical background who present with acute onset of right iliac fossa (RIF) pain. Examination revealed tenderness over the right iliac fossa and was having localized rebound. His inflammatory markers were high. He was successfully treated with laparoscopy surgery and he was subsequently discharged the following day.

Abstract 1122‐000051: Isolated Diplacusis Due to Ipsilateral Temporal Lobe Infarction: A Case Report

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Ali Kerro ◽  
Reza Bavarsad Shahripour
Keyword(s):  
Case Report ◽  
Temporal Lobe ◽  
Case Reports ◽  
Sensorineural Deafness ◽  
Screen Test ◽  
Acute Onset ◽  
First Case ◽  
Ischemic Infarct ◽  
Pubmed Search ◽  
The Right

Introduction : Double hearing or Diplacusis is a synchronous double perception of a sound and can have Binauralis or Monauralis pattern, with inner ear disorders being the main culprit [1] . Other forms of Auditory illusions have been reported as a co‐manifestation of stroke syndromes, but none as an isolated presentation [1][2] . This is a case of a 77‐year‐old male with acute onset isolated Diplacusis in a patient due to a right temporal lobe ischemic infarct. To our knowledge, this is the first case report of an isolated diplacusis due to cortical infarct. Methods : A case presentation with Pubmed search of review articles and case reports. Results : The patient had a past medical history of sensorineural deafness in his left ear. He described any sound heard as the same quality but occurring with an echo heard a fraction of a second later in his right ear. There was no decreased hearing quality or tinnitus reported in his right ear. His drug screen test was negative. His examination was only remarkable for a sensorineural hearing loss pattern on his left ear. His (NIHSS) was zero, and no other cranial nerve abnormalities were detected. His MRI was significant for a punctate restricted diffusion on the right temporal lobe, resembling an ischemic infarct (Figure). Conclusions : Isolated diplacusis can present as acute ischemic stroke in the temporal lobe. Further studies are needed to understand its pathophysiology.

Meningeal Melanocytoma Associated with Ipsilateral Nevus of Ota Presenting as Intracerebral Hemorrhage: Case Report

Neurosurgery ◽  
2005 ◽  
Vol 56 (6) ◽  
pp. E1376-E1376 ◽  
Author(s):  
Ken Hino ◽  
Motoo Nagane ◽  
Yasunori Fujioka ◽  
Yoshiaki Shiokawa
Keyword(s):  
Intracerebral Hemorrhage ◽  
Intracerebral Hematoma ◽  
Current Case ◽  
Meningeal Melanocytoma ◽  
Nevus Of Ota ◽  
First Case ◽  
Resected Tumor ◽  
History Of ◽  
The Right ◽  
High Level

Abstract OBJECTIVE AND IMPORTANCE: The authors report a rare case of meningeal melanocytoma presenting with unconsciousness, which was caused by an intracerebral hematoma and associated with a history of ipsilateral nevus of Ota. CLINICAL PRESENTATION: A 75-year-old woman developed nevus of Ota in the first and second divisions of the right trigeminal nerve territory, which had been treated with a skin graft 40 years earlier. She noticed right exophthalmos but left it untreated for 2 years and then became comatose owing to orbital and intracranial tumors, the latter manifesting with hemorrhage. INTERVENTION: She underwent craniotomy, during which the tumor was partially removed with intracerebral hematoma. Histopathologically, the tumor was diagnosed as meningeal melanocytoma. Western blot analysis demonstrated a retained protein expression of cell cycle inhibitor p16INK4A and a high level of antiapoptotic Bcl-2 in the resected tumor. CONCLUSION: The combination of nevus of Ota and meningeal melanocytoma has been reported in only four cases in the literature, including the current case. This is the first case coinciding with intracerebral hemorrhage, suggesting the necessity for careful follow-up with radiological images.

scholarly journals Acute Macular Neuroretinopathy Related to Alcoholic Hepatitis

2021 ◽  
pp. 293-298
Author(s):  
Grace Anne Mc Cabe ◽  
William Gordon Campbell ◽  
Thomas Gordon Campbell
Keyword(s):  
Alcoholic Hepatitis ◽  
Plexiform Layer ◽  
Acute Onset ◽  
Acute Macular Neuroretinopathy ◽  
Microvascular Changes ◽  
First Case ◽  
Paracentral Scotoma ◽  
The Right ◽  
Sd Oct ◽  
Subfoveal Fluid

A 33-year-old woman admitted for acute alcoholic hepatitis was referred to the ophthalmology department with an acute onset paracentral scotoma of the left eye. On examination, best-corrected visual acuity was Snellen 6/4 in the right eye and 6/9 in the left eye. Dilated left fundus examination revealed wedge-shaped changes at the macula. Spectral-domain ocular coherence tomography (SD-OCT) initially revealed a small cuff of subfoveal fluid and band-like hyperreflectivity extending outwards from the outer plexiform layer consistent with acute macular neuroretinopathy (AMN). Four days later, repeat SD-OCT was performed and it demonstrated resolution of the subfoveal fluid and disruption of the outer retinal layers. At the 6-week follow-up, the patient had no improvement in her symptoms and OCT angiography demonstrated coarsening and microvascular changes in both the deep vascular plexus and the choriocapillaris. To our knowledge, this is the first case of AMN in association with acute hepatitis. Although the exact pathophysiology of AMN remains obscure, this case highlights the benefits of multimodal retinal imaging and aims to bring attention to the possible association of AMN with alcoholic hepatitis.

scholarly journals Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines

2021 ◽  
Author(s):  
Jae-Sung Yi ◽  
Sravan Perla ◽  
Yan Huang ◽  
Kana Mizuno ◽  
Frank J. Giordano ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Transcriptome Analysis ◽  
Noonan Syndrome ◽  
Low Dose ◽  
Cardiac Fibrosis ◽  
Heart Tissue ◽  
Sh2 Domain ◽  
Autosomal Dominant Disorder ◽  
Multiple Lentigines ◽  
Dasatinib Treatment

Abstract Purpose Noonan syndrome with multiple lentigines (NSML) is an autosomal dominant disorder presenting with hypertrophic cardiomyopathy (HCM). Up to 85% of NSML cases are caused by mutations in the PTPN11 gene that encodes for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP2). We previously showed that low-dose dasatinib protects from the development of cardiac fibrosis in a mouse model of NSML harboring a Ptpn11Y279C mutation. This study is performed to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a low-dose of dasatinib in NSML mice and to determine its effectiveness in ameliorating the development of HCM. Methods Dasatinib was administered intraperitoneally into NSML mice with doses ranging from 0.05 to 0.5 mg/kg. PK parameters of dasatinib in NSML mice were determined. PD parameters were obtained for biochemical analyses from heart tissue. Dasatinib-treated NSML mice (0.1 mg/kg) were subjected to echocardiography and assessment of markers of HCM by qRT-PCR. Transcriptome analysis was performed from the heart tissue of low-dose dasatinib-treated mice. Results Low-dose dasatinib exhibited PK properties that were linear across doses in NSML mice. Dasatinib treatment of between 0.05 and 0.5 mg/kg in NSML mice yielded an exposure-dependent inhibition of c-Src and PZR tyrosyl phosphorylation and inhibited AKT phosphorylation. We found that doses as low as 0.1 mg/kg of dasatinib prevented HCM in NSML mice. Transcriptome analysis identified differentially expressed HCM-associated genes in the heart of NSML mice that were reverted to wild type levels by low-dose dasatinib administration. Conclusion These data demonstrate that low-dose dasatinib exhibits desirable therapeutic PK properties that is sufficient for effective target engagement to ameliorate HCM progression in NSML mice. These data demonstrate that low-dose dasatinib treatment may be an effective therapy against HCM in NSML patients.

Ibrutinib-related uveitis: A report of two severe cases

2021 ◽  
pp. 112067212110012
Author(s):  
Marcela Bohn ◽  
Luciano Bravo-Ljubetic ◽  
Richard W J Lee ◽  
Harry Petrushkin
Keyword(s):  
Anterior Uveitis ◽  
Subretinal Fluid ◽  
Acute Onset ◽  
Steroid Treatment ◽  
Oral Steroid ◽  
Temporal Association ◽  
Drug Induced ◽  
Cardiac Side Effects ◽  
First Case ◽  
The Right

Introduction: Ibrutinib is a small-molecule drug approved for the treatment of haematological disorders and is known to be associated with visual disturbances, but uveitis has not yet been reported as an adverse effect of this medication. We present two cases of ibrutinib-associated severe uveitis in patients with chronic lymphocytic leukaemia. Case description: Our first case is a 65-year-old woman who presented with acute onset of bilateral fibrinous anterior uveitis 1 day after starting ibrutinib. Her vision was hand movements in the right eye and 20/120 in the left with hyperaemic discs and subretinal fluid. Ibrutinib was stopped and she experienced a significant improvement under local and oral steroid treatment. The second case is a 64-year-old male with subacute onset of bilateral hypertensive anterior uveitis with pupillary seclusion and right eye hyphaema. He was on ibrutinib for the past 9 months. His vision at presentation was 20/80 and 20/60 for the right and left eye, respectively. He responded poorly to local steroid treatment until ibrutinib was stopped due to cardiac side-effects, after which his uveitis resolved and treatment was stopped. Conclusion: The temporal association between changes in ibrutinib treatment and our patients’ ocular inflammation suggests a causative link. Ibrutinib increases Th1-based immune responses which is proposed as a mechanism for drug-induced uveitis. Its antiplatelet effect may explain the fibrinous nature of the inflammation and hyphaema.

Abstract 198: Aberrant Endothelial-myocardial Crosstalk Causes Hypertrophy in Noonan Syndrome With Multiple Lentigines

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jessica Lauriol ◽  
Janel R Cabrera ◽  
Gabriel C Segarra ◽  
Meaghan E Flessa ◽  
Lauren E Miller ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Noonan Syndrome ◽  
Cardiac Development ◽  
Tyrosine Phosphatase ◽  
Adult Onset ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Specific Expression ◽  
Underlying Mechanisms ◽  
Multiple Lentigines

Congenital heart disease (CHD) is the most common birth defect worldwide; however, underlying mechanisms remain unknown. Loss-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP2, are implicated in CHD and cause Noonan Syndrome with Multiple Lentigines (NSML). NSML presents with multiple cardiac defects, including hypertrophy. Here, we found that the NSML-associated adult-onset cardiac hypertrophy stems from aberrant signaling originating from developing endocardium. Embryonic NSML hearts showed diminished trabeculation and valvular hyperplasia, defects recapitulated in endocardial-, but not myocardial- or neural crest-, specific NSML mice. NSML hearts also developed ventricular septal defects, a phenotype reproduced only in myocardial-specific NSML hearts, suggesting NSML mutations have both cell autonomous and non-autonomous functions in cardiac development. Importantly, endocardial-specific expression of NSML was sufficient to induce adult-onset cardiac hypertrophy. Mechanistically, we observed aberrant AKT activity in NSML embryos, with decreased downstream FOXP1/FGF and NOTCH1/EPHB2 signaling, two pathways necessary for reciprocal crosstalk between developing endocardium and myocardium. Taken together, our data provide the first functional and disease-based evidence to suggest that critical mechanisms exist to control endocardial-myocardial crosstalk, the aberrant regulation of which may lead to CHD and adult-onset cardiac disease.

scholarly journals A First Case Report of Subependymoma in PTPN11 Mutation-Associated Noonan Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Boonchai Boonyawat ◽  
Mongkon Charoenpitakchai ◽  
Piradee Suwanpakdee
Keyword(s):  
Case Report ◽  
Noonan Syndrome ◽  
Fourth Ventricle ◽  
Somatic Mutations ◽  
Autosomal Dominant ◽  
Hematologic Malignancies ◽  
Autosomal Dominant Disorder ◽  
Ptpn11 Mutation ◽  
First Case ◽  
Tumor Types

Noonan syndrome (NS) is an autosomal dominant disorder in some cases caused by PTPN11 mutations. Since somatic mutations in PTPN11 are seen in several tumor types, NS which causes germline PTPN11 mutations are also increase the risk of hematologic malignancies and brain solid tumors. However, the report of brain tumors in Noonan syndrome remains rather rare. Here, we report the first case of an 11-year-old Thai boy with Noonan syndrome who presented with symptoms related to hydrocephalus secondary to subependymoma in the fourth ventricle, and PTPN11 mutation was identified in this patient.

scholarly journals LEOPARD Syndrome with PTPN11 Gene Mutation in Three Family Members Presenting with Different Phenotypes

2019 ◽  
Vol 09 (04) ◽  
pp. 246-251
Author(s):  
Nuha Alfurayh ◽  
Fahad Alsaif ◽  
Nouf Alballa ◽  
Leena Zeitouni ◽  
Khushnooda Ramzan ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Family Members ◽  
Leopard Syndrome ◽  
Autosomal Dominant Disorder ◽  
Ptpn11 Gene ◽  
Ptpn11 Mutation ◽  
Two Generations ◽  
Generation Sequencing ◽  
Multiple Lentigines

AbstractLEOPARD syndrome (LS) is a rare autosomal dominant disorder that is characterized by multiple lentigines and various congenital anomalies. The clinical diagnosis of LS requires molecular confirmation. The most frequently reported mutations in LS patients are in the protein tyrosine phosphatase nonreceptor type 11 gene, PTPN11. Herein, we report the cases of three family members from two generations who are affected by LS and all carry the PTPN11 mutation c.836A > G (p.Tyr279Cys), identified by next-generation sequencing, while exhibiting different phenotypes.

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