[Azygos vein aneurysm: An unusual and rare diagnostic].

Rev Pneumol Clin. 2016 May;72(3):217-9

Authors: Alberti N, Petitpierre F, Crombe A, Bernard S, Sironneau S

PMID: 27133177 [PubMed - indexed for MEDLINE]

Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.

Muscle Nerve. 2017 May;55(5):761-765

Authors: Mehta P, Küspert M, Bale T, Brownstein CA, Towne MC, De Girolami U, Shi J, Beggs AH, Darras BT, Wegner M, Piao X, Agrawal PB

Abstract
INTRODUCTION: Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy that presents in the neonatal period and has been linked previously to mutations in several genes associated with myelination. A recent study has linked 4 homozygous frameshift mutations in the contactin-associated protein 1 (CNTNAP1) gene with this condition.
METHODS: We report a neonate with CHN who was found to have absent sensory nerve and compound muscle action potentials and hypomyelination on nerve biopsy.
RESULTS: On whole exome sequencing, we identified a novel CNTNAP1 homozygous missense mutation (p.Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a β-strand to cause an unstable structure and likely significant changes in protein function.
CONCLUSIONS: This report links a missense CNTNAP1 variant to the disease phenotype previously associated only with frameshift mutations. Muscle Nerve 55: 761-765, 2017.

PMID: 27668699 [PubMed - indexed for MEDLINE]

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Clin Pharmacol Ther. 2016 Aug;100(2):160-9

Authors: Bush WS, Crosslin DR, Owusu-Obeng A, Wallace J, Almoguera B, Basford MA, Bielinski SJ, Carrell DS, Connolly JJ, Crawford D, Doheny KF, Gallego CJ, Gordon AS, Keating B, Kirby J, Kitchner T, Manzi S, Mejia AR, Pan V, Perry CL, Peterson JF, Prows CA, Ralston J, Scott SA, Scrol A, Smith M, Stallings SC, Veldhuizen T, Wolf W, Volpi S, Wiley K, Li R, Manolio T, Bottinger E, Brilliant MH, Carey D, Chisholm RL, Chute CG, Haines JL, Hakonarson H, Harley JB, Holm IA, Kullo IJ, Jarvik GP, Larson EB, McCarty CA, Williams MS, Denny JC, Rasmussen-Torvik LJ, Roden DM, Ritchie MD

Abstract
Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

PMID: 26857349 [PubMed - indexed for MEDLINE]

Desmoid-Type Fibromatosis: Who, When, and How to Treat.

Curr Treat Options Oncol. 2017 May;18(5):29

Authors: Martínez Trufero J, Pajares Bernad I, Torres Ramón I, Hernando Cubero J, Pazo Cid R

Abstract
OPINION STATEMENT: Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/β-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.

PMID: 28439797 [PubMed - in process]

Plasmablastic lymphoma: an atypical cutaneous presentation of a rare entity.

Dermatol Online J. 2016 May 15;22(5):

Authors: Mota F, Mesquita B, Carvalho S, Coelho A, Velho G, Lima M, Selores M

Abstract
Plasmablastic lymphoma is a very rare B-cell lymphoma typically associated with immunosuppression: It occurs primarily in the oral cavity, although some cases were reported in other organs and tissues.To date, only 10 cases of primary cutaneous plasmablastic lymphoma have been described. Clinically, primary cutaneous plasmablastic lymphoma presents as non-specific cutaneous lesions (purple nodules, erythematous infiltrated plaques). In previously described cases, as in this case, histology and immunohistochemistry are required to make the diagnosis. Owing to the rarity of this entity, there is no established therapy, which makes its management an individualized, patient-based decision.

PMID: 27617520 [PubMed - indexed for MEDLINE]

[Sternal fracture in growing children : A rare and often overlooked fracture? Documentation of four cases].

Unfallchirurg. 2016 Jul;119(7):570-4

Authors: Fichtel I, Fernandez FF, Wirth T

Abstract
BACKGROUND: Sternal fractures in childhood are rare. The aim of the study was to investigate the accident mechanism, the detection of radiological and sonographical criteria and consideration of associated injuries.
METHOD: In the period from January 2010 to December 2012 all inpatients and outpatients with sternal fractures were recorded according to the documentation.
RESULTS: A total of 4 children aged 5-14 years with a sternal fracture were treated in 2 years, 2 children were hospitalized for pain management and 2 remained in outpatient care.
CONCLUSION: Isolated sternal fractures in childhood are often due to typical age-related traumatic incidents. Ultrasonography is a useful diagnostic tool for fracture detection and radiography is the method of choice for visualization of the extent of the dislocation.

PMID: 25277731 [PubMed - indexed for MEDLINE]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/04/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

[Malignant rhabdoid tumor of the lung].

Rev Mal Respir. 2016 Nov;33(9):808-811

Authors: Zysman M, Clement-Duchene C, Bastien C, Vaillant P, Martinet Y

Abstract
INTRODUCTION: Rhabdoid tumours usually develop in brain and spinal cord or kidney; they are highly malignant neoplasms that typically arise in infancy and early childhood. However, rare cases of pulmonary localization have been described, particularly among young adults.
CASE REPORT: A 26-year-old man, smoker, had a right apical lung mass associated with a Pancoast syndrome leading to haemoptysis. There was also a tumour of the left thigh and scalp. Histological samples taken at these three locations were in favour of an undifferentiated carcinoma. The lack of nuclear integrase interactor 1 expression, and immunohistochemical appearance supported the diagnosis of rhabdoid tumour. Despite treatment, unfavourable progression confirmed this hypothesis, doubling time was less than six weeks with development of multiple metastases resulted in death within only three months after diagnosis.
CONCLUSION: The lack of expression of integrase interactor 1 should suggest the diagnosis of rhabdoid tumour, especially when there is quick progression. The prognosis of these tumours remains poor and therapeutic options are limited.

PMID: 27595391 [PubMed - indexed for MEDLINE]

A rare occurrence of intramasseteric schwannoma - case report and literature review.

Rev Stomatol Chir Maxillofac Chir Orale. 2016 Jun;117(3):170-2

Authors: Wang HK, Gong YL, Wang RX, Zheng XT, Huang SY, Zhang DS

Abstract
A schwannoma is a benign, solitary, well-defined, painless, slowly-enlarging nerve sheath tumor, composed of Schwann cells. Intramasseteric localization is very unusual. We report the case of a 33-year-old male who developed an intramasseteric schwannoma. Tumor could be completely removed under general anesthesia. Histopathological examination made the diagnosis of intramasseteric schwannoma through the presence of Antoni A areas and Verocay bodies. The diagnosis of schwannoma should be taken into consideration in case of parotideomasseteric tumors.

PMID: 27155941 [PubMed - indexed for MEDLINE]

[NK/T-cell Lymphoma of nasal-type: A rare affection with a poor prognosis].

Rev Stomatol Chir Maxillofac Chir Orale. 2016 Jun;117(3):167-9

Authors: Doh K, Tagba E, Thiam I, Sarr A, Woto-Gaye G

Abstract
INTRODUCTION: NK/T cell lymphoma of nasal-type was described in 1933 as a malignant midfacial granuloma. The diagnosis of this rare affection is clinical and immunohistopathological. We report a case of NK/T cell lymphoma diagnosed at an advanced stage.
OBSERVATION: A 60-year-old man with no particular medical history presented since seven months with a left nasal obstruction associated with a purulent and fetid rhinorrhea followed by a centrifugal midfacial necrosis. Blood tests showed an inflammatory syndrome. The CT-scan of the face showed a filling of the nose and sinus by a tissular process and a lysis of the bone walls. Three series of biopsies (le last being performed under general anesthesia) were necessary to get the diagnosis of NK/T cell lymphoma. The standard histology showed a malignant proliferation made of round and spindle-shaped lymphoid-like cells and angiocentric arrangement. The cells were CD 2+, CD 3+, CD 5+ and CD 56+. The spontaneous evolution was fatal one month after diagnosis in a context of septic shock.
CONCLUSION: NK/T cell lymphoma of nasal-type is a rare disease but should be evocated in patient with midfacial necrosis of centrifugal evolution. The diagnosis certainty is made on immunohistopathological analysis. Multiple biopsies, made at distance from necrotic areas and under general anesthesia may be necessary.

PMID: 26972561 [PubMed - indexed for MEDLINE]

Information ranks highest: Expectations of female adolescents with a rare genital malformation towards health care services.

PLoS One. 2017;12(4):e0174031

Authors: Simoes E, Sokolov AN, Kronenthaler A, Hiltner H, Schaeffeler N, Rall K, Ueding E, Rieger MA, Wagner A, Poesch LS, Baur MC, Kittel J, Brucker SY

Abstract
BACKGROUND: Access to highly specialized health care services and support to meet the patient's specific needs is critical for health outcome, especially during age-related transitions within the health care system such as with adolescents entering adult medicine. Being affected by an orphan disease complicates the situation in several important respects. Long distances to dedicated institutions and scarcity of knowledge, even among medical doctors, may present major obstacles for proper access to health care services and health chances. This study is part of the BMBF funded TransCareO project examining in a mixed-method design health care provisional deficits, preferences, and barriers in health care access as perceived by female adolescents affected by the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), a rare (orphan) genital malformation.
METHODS: Prior to a communicative validation workshop, critical elements of MRKHS related care and support (items) were identified in interviews with MRKHS patients. During the subsequent workshop, 87 persons involved in health care and support for MRKHS were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1, strongly disagree) as to 1) the elements' potential importance (i.e., health care expected to be "best practice", or priority) and 2) the presently experienced care. A gap score between the two was computed highlighting fields of action. Items were arranged into ten separate questionnaires representing domains of care and support (e.g., online-portal, patient participation). Within each domain, several items addressed various aspects of "information" and "access". Here, we present the outcome of items' evaluation by patients (attended, NPAT = 35; respondents, NRESP = 19).
RESULTS: Highest priority scores occurred for domains "Online-Portal", "Patient participation", and "Tailored informational offers", characterizing them as extremely important for the perception as best practice. Highest gap scores yielded domains "Tailored informational offers", reflecting perceived lack of disease-related information for affected persons, medical experts, and health insurance companies, "Online-Portal" (with limited information available on specialist clinics and specialized doctors), and regarding insufficient support offers (e.g., in school and occupational settings). Conversely, lowest gap scores were found with group offers for MRKHS patients ("Transition programs") and MRKHS self-help days ("Patient participation"), suggesting satisfaction or good solutions in place.
DISCUSSION: The importance assigned to disease-related information indicates that informational deficits are perceived by patients as barriers, hindering proper access to health care, especially in an orphan disease. Access to health-related information plays a role for all persons seeking help and care. However, the overwhelmingly high scores attributed to these elements in the context of an orphan disease reveal that here improved information policies are crucial, demanding for institutionalized solutions supported by the health care system.
IMPLICATIONS FOR PRACTICE: The disparity between experience of care and attribution as best practice detected describes areas of action in all domains involved, highlighting information related fields. New concepts and structures for health care in orphan diseases could draw upon these patient-oriented results a) regarding orphan-disease specific elements demanding institutionalized reimbursement, b) essential elements for center care and corresponding networks, and c) elements reflecting patients´ participation in the conception of centers for rare diseases.

PMID: 28426677 [PubMed - in process]

Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.

Sci Transl Med. 2017 Apr 19;9(386):

Authors: Cummings BB, Marshall JL, Tukiainen T, Lek M, Donkervoort S, Foley AR, Bolduc V, Waddell LB, Sandaradura SA, O'Grady GL, Estrella E, Reddy HM, Zhao F, Weisburd B, Karczewski KJ, O'Donnell-Luria AH, Birnbaum D, Sarkozy A, Hu Y, Gonorazky H, Claeys K, Joshi H, Bournazos A, Oates EC, Ghaoui R, Davis MR, Laing NG, Topf A, Genotype-Tissue Expression Consortium, Kang PB, Beggs AH, North KN, Straub V, Dowling JJ, Muntoni F, Clarke NF, Cooper ST, Bönnemann CG, MacArthur DG

Abstract
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples. We demonstrate the power of RNA-seq to validate candidate splice-disrupting mutations and to identify splice-altering variants in both exonic and deep intronic regions, yielding an overall diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo intronic mutation in COL6A1 that results in a dominantly acting splice-gain event, disrupting the critical glycine repeat motif of the triple helical domain. We identify this pathogenic variant in a total of 27 genetically unsolved patients in an external collagen VI-like dystrophy cohort, thus explaining approximately 25% of patients clinically suggestive of having collagen VI dystrophy in whom prior genetic analysis is negative. Overall, this study represents a large systematic application of transcriptome sequencing to rare disease diagnosis and highlights its utility for the detection and interpretation of variants missed by current standard diagnostic approaches.

PMID: 28424332 [PubMed - in process]

Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving the German Surveillance Unit for Rare Diseases in Childhood.

Pediatr Infect Dis J. 2017 May;36(5):451-456

Authors: Grote V, Silier CC, Voit AM, Jansson AF

Abstract
BACKGROUND: Although bacterial osteomyelitis (BO) is a commonly recognized diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial osteitis (NBO). The goal of our study was to distinguish between the 2 disease entities and better define NBO.
METHODS: Using the German Surveillance Unit for Rare Diseases in Childhood (Erhebungseinheit für Seltene Paediatrische Erkrankungen in Deutschland), this prospective study during a 5-year period captured 657 patients at first diagnosis of either BO (n = 378) or NBO (n = 279) while analyzing epidemiologic, clinical and radiologic data.
RESULTS: BO was reported in 1.2 per 100,000 children with a higher prevalence in younger male patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients tended to present with fevers (68%), elevated inflammation markers (82%) and local swelling (62%) but a shorter course of symptoms than NBO patients. NBO patients presented in good general health (86%) and were more likely to have multifocal lesions (66%). Staphylococcus aureus was the most prominent pathogen (83%), with only one methicillin-resistant S. aureus reported. Complications ranged from arthritis adjacent to the lesion to hyperostosis and vertebral fractures.
CONCLUSIONS: BO and NBO can be distinguished based on symptoms, associated diseases and inflammation markers. NBO should always be considered in pediatric patients presenting with bone lesions and pain, especially in young female patients presenting with good general health, minimal inflammation markers and multifocal lesions in the vertebrae, clavicle and sternum.

PMID: 28403046 [PubMed - indexed for MEDLINE]

Interoperability Architecture for a Paediatric Oncology European Reference Network.

Stud Health Technol Inform. 2016;223:39-45

Authors: Nitzlnader M, Canete Nieto A, Ribelles AJ, Brunmair B, Ladenstein R, Schreier G

Abstract
With the Directive 2011/24/EU on patients' rights in cross-border healthcare and the related delegated decisions, the European Commission defined a legal framework on how healthcare shall be organised by European Union (EU) member states (MS) where patients can move beyond the borders of their home country. Among other aspects, Article 12 of the directive is concerned with supporting MS with the development of so called European Reference Networks (ERN), dedicated to the treatment of "patients with a medical condition requiring a particular concentration of expertise in medical domains where expertise is rare". In the "European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment" (ExPO-r-Net) project, the establishment of such an ERN in the domain of Paediatric Oncology is currently piloted. The present paper describes the high level use cases, the main requirements and a corresponding interoperability architecture capable to serve as the necessary IT platform to facilitate cross-border health data exchange.

PMID: 27139383 [PubMed - indexed for MEDLINE]

A rare case of necrotizing fasciitis caused by Vibrio cholerae O8 in an immunocompetent patient.

Wien Klin Wochenschr. 2016 Oct;128(19-20):728-730

Authors: Dobrović K, Rudman F, Ottaviani D, Šestan Crnek S, Leoni F, Škrlin J

Abstract
We report a case of necrotizing fasciitis of the leg caused by Vibrio cholerae O8 in a 63-year-old immunocompetent man after he had been fishing in a lake on a Croatian island. The strain was cytotoxic, invasive and adhesive and contained a fragment of the gene for El Tor-like hemolysin (El Tor hlyA). After surgical and antibiotic treatment, the patient fully recovered.

PMID: 27604649 [PubMed - indexed for MEDLINE]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/04/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Double Extramedullary Plasmacytoma of the Stomach with a Long-term Endoscopic Follow-up.

Intern Med. 2016;55(24):3585-3590

Authors: Doi A, Sumiyoshi T, Omori Y, Oyamada Y, Kumano K, Yoshizaki N, Hirayama M, Suzuki Y, Okushiba S, Kogawa T, Doi T, Kondo H

Abstract
A 56-year-old woman was referred to our hospital with a growing gastric submucosal tumor. An upper endoscopic examination revealed two gastric tumors, an original polypoid tumor and a newly diagnosed superficial tumor. Boring biopsied specimens of the submucosal tumor showed gastric plasmacytoma; however, the other specimens showed no malignancy. Blood diseases were ruled out using various examinations; therefore, we diagnosed the tumor as extramedullary gastric plasmacytoma. The patient underwent laparoscopic distal gastrectomy, and both tumors were thus revealed to be plasmacytomas. We experienced a rare case with two differently shaped extramedullary gastric plasmacytomas without significant morphologic change during the follow-up.

PMID: 27980257 [PubMed - indexed for MEDLINE]

Establishment of a bleeding score as a diagnostic tool for patients with rare bleeding disorders.

Thromb Res. 2016 Dec;148:128-134

Authors: Palla R, Siboni SM, Menegatti M, Musallam KM, Peyvandi F, European Network of Rare Bleeding Disorders (EN-RBD) group

Abstract
INTRODUCTION: Bleeding manifestations among patients with rare bleeding disorders (RBDs) vary significantly between disorders and patients, even when affected with the same disorder. In response to the challenge represented by the clinical assessment of the presence and severity of bleeding symptoms, a number of bleeding score systems (BSSs) or bleeding assessment tools (BATs) were developed. The majority of these were specifically developed for patients with more common bleeding disorders than RBDs. Few RBDs patients were evaluated with these tools and without conclusive results.
METHODS: A new BSS was developed using data retrieved from a large group of patients with RBDs enrolled in the EN-RBD database and from healthy subjects. These data included previous bleeding symptoms, frequency, spontaneity, extent, localization, and relationship to prophylaxis and acute treatment. The predictive power of this BSS was also compared with the ISTH-BAT and examined for the severity of RBDs based on coagulant factor activity.
RESULTS: This BSS was able to differentiate patients with RBDs from healthy individuals with a bleeding score value of 1.5 having the highest sum of sensitivity (67.1%) and specificity (73.8%) in discriminating patients with RBD from those without. An easy-to-use calculation was also developed to assess the probability of having a RBD. Its comparison with the ISTH-BAT confirmed its utility. Finally, in RBDs patients, there was a significant negative correlation between BS and coagulant factor activity level, which was strongest for fibrinogen and FXIII deficiencies.
CONCLUSION: The use of this quantitative method may represent a valuable support tool to clinicians.

PMID: 27855295 [PubMed - indexed for MEDLINE]

New funding cap for cancer drugs.

Nurs Stand. 2016 Jun 01;30(40):22-3

Authors: Dix A

PMID: 27275892 [PubMed - indexed for MEDLINE]

Rare presentation of pseudosequestration in childhood: CT and CT angiography findings.

Clin Respir J. 2017 Jan;11(1):113-116

Authors: Gormez A, Ozcan HN, Oguz B, Yalçın E, Ariyurek M, Haliloglu M, Emiralioglu N

Abstract
Anomalous systemic arterial supply to the lungs with normal bronchial branching and pulmonary arterial supply is an unusual variant of the sequestration spectrum. Pseudosequestration is referred as the combination of systemic arterial supply to lung with normal bronchial connection. Thorax computed tomography (CT) and CT angiography are non-invasive and useful techniques in making the definitive diagnosis. Herein, we report two paediatric patients with anomalous systemic arterial supply to normal basal segments of the lower lobes.

PMID: 25833377 [PubMed - indexed for MEDLINE]