Adult xanthogranulomatous disease of the orbit: case report of spontaneous regression and review of treatment modalities.

Orbit. 2020 Feb;39(1):31-37

Authors: Maeng MM, Godfrey KJ, Jalaj S, Kazim M

Abstract
Adult xanthogranulomatous disease of the orbit is a rare and incompletely understood entity. It can be limited to the orbit or be associated with systemic disease. While routine systemic surveillance is the standard of care for patients with orbital xanthogranulomatous disease, there is no universally accepted protocol for managing periorbital and orbital involvement. The authors report a case of adult orbital xanthogranuloma, without systemic disease, who, after 10 years of observation, demonstrated sustained radiographic regression of the lesions. To the authors' knowledge, this represents one of the first reports of spontaneous regression of untreated orbital xanthogranuloma, and supports observation of lesions that do not compromise ocular function. We present our case in the context of a major review of various treatment strategies described in the literature, including surgical resection, radiotherapy, plasmapheresis, corticosteroids, multiple immunomodulatory medications.

PMID: 31021176 [PubMed - indexed for MEDLINE]

Orbital AL amyloid.

Orbit. 2020 Feb;39(1):68-70

Authors: Chan TM, Prospero Ponce CM, Allen RC, Bell D, Lee AG

Abstract
Amyloidosis and lymphoma localized to the ocular adnexa are rare, and their presentation may resemble more common inflammatory conditions such as autoimmune disease or infection, which can protract diagnostic evaluation and delay eventual therapy. In a patient with recalcitrant facial and tooth pain and ophthalmoplegia, evaluation should include careful histopathologic analysis of biopsy specimens. We report a case of orbital AL amyloidosis associated with localized lymphoma that presented with intractable dental pain and progressed to bilateral complete ophthalmoplegia.

PMID: 31020884 [PubMed - indexed for MEDLINE]

Pseudocystic appearance of an orbital carcinoid metastasis.

Orbit. 2020 Feb;39(1):41-44

Authors: Halliday LA, Curragh D, Sia PI, Selva D

Abstract
Carcinoid tumours are a low-grade neuroendocrine malignancy that infrequently metastisizes to orbital structures. The typical radiological appearance of carcinoid is a solid, well-circumscribed mass that enhances with contrast. We present a case of orbital carcinoid metastasis with pseudocystic radiological appearance and review of the literature.

PMID: 30747028 [PubMed - indexed for MEDLINE]

Effect of serotonin modulation on dystrophin-deficient zebrafish.

Biol Open. 2020 Jul 27;:

Authors: Spinazzola JM, Lambert MR, Gibbs DE, Conner JR, Krikorian GL, Pareek P, Rago C, Kunkel LM

Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and reapplication of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants, and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies.

PMID: 32718931 [PubMed - as supplied by publisher]

Rapid development of bullous lung disease: a complication of electronic cigarette use.

Thorax. 2020 04;75(4):359

Authors: Kalra SS, Pais F, Harman E, Urbine D

PMID: 32041740 [PubMed - indexed for MEDLINE]

Where Will Statistical Sciences for Clinical Pharmacology Be in 2030?

Clin Pharmacol Ther. 2020 01;107(1):17-21

Authors: Smith BP

PMID: 31863686 [PubMed - indexed for MEDLINE]

Updating the neurodevelopmental profile of Alazami syndrome: Illustrating the role of developmental assessment in rare genetic disorders.

Am J Med Genet A. 2019 08;179(8):1565-1569

Authors: Wojcik MH, Linnea K, Stoler JM, Rappaport L

Abstract
Alazami syndrome, caused by biallelic pathogenic variants in LARP7, is a recently-described rare genetic disorder, with 17 patients currently reported in the literature. We present a case of a male infant referred for genetics evaluation at 5 months of age, found at 17 months of age to have Alazami syndrome. He was promptly referred for developmental evaluation, where he was found to be higher functioning than prior reports of individuals with this condition. This demonstrates the neurodevelopmental phenotypic variability seen in rare genetic disorders; it also demonstrates the important role of developmental programs to measure and track outcomes and provide support for infants with genetic disorders that put them at risk of developmental disabilities.

PMID: 31074943 [PubMed - indexed for MEDLINE]

15 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 2020/07/28

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.

15 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 2020/07/28

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.

Human iPSC Modeling Reveals Mutation-Specific Responses to Gene Therapy in a Genotypically Diverse Dominant Maculopathy.

Am J Hum Genet. 2020 Jul 20;:

Authors: Sinha D, Steyer B, Shahi PK, Mueller KP, Valiauga R, Edwards KL, Bacig C, Steltzer SS, Srinivasan S, Abdeen A, Cory E, Periyasamy V, Siahpirani AF, Stone EM, Tucker BA, Roy S, Pattnaik BR, Saha K, Gamm DM

Abstract
Dominantly inherited disorders are not typically considered to be therapeutic candidates for gene augmentation. Here, we utilized induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) to test the potential of gene augmentation to treat Best disease, a dominant macular dystrophy caused by over 200 missense mutations in BEST1. Gene augmentation in iPSC-RPE fully restored BEST1 calcium-activated chloride channel activity and improved rhodopsin degradation in an iPSC-RPE model of recessive bestrophinopathy as well as in two models of dominant Best disease caused by different mutations in regions encoding ion-binding domains. A third dominant Best disease iPSC-RPE model did not respond to gene augmentation, but showed normalization of BEST1 channel activity following CRISPR-Cas9 editing of the mutant allele. We then subjected all three dominant Best disease iPSC-RPE models to gene editing, which produced premature stop codons specifically within the mutant BEST1 alleles. Single-cell profiling demonstrated no adverse perturbation of retinal pigment epithelium (RPE) transcriptional programs in any model, although off-target analysis detected a silent genomic alteration in one model. These results suggest that gene augmentation is a viable first-line approach for some individuals with dominant Best disease and that non-responders are candidates for alternate approaches such as gene editing. However, testing gene editing strategies for on-target efficiency and off-target events using personalized iPSC-RPE model systems is warranted. In summary, personalized iPSC-RPE models can be used to select among a growing list of gene therapy options to maximize safety and efficacy while minimizing time and cost. Similar scenarios likely exist for other genotypically diverse channelopathies, expanding the therapeutic landscape for affected individuals.

PMID: 32707085 [PubMed - as supplied by publisher]

European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants.

Orphanet J Rare Dis. 2019 11 21;14(1):264

Authors: van de Laar IMBH, Arbustini E, Loeys B, Björck E, Murphy L, Groenink M, Kempers M, Timmermans J, Roos-Hesselink J, Benke K, Pepe G, Mulder B, Szabolcs Z, Teixidó-Turà G, Robert L, Emmanuel Y, Evangelista A, Pini A, von Kodolitsch Y, Jondeau G, De Backer J

Abstract
The ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits.Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2.The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.

PMID: 31752940 [PubMed - indexed for MEDLINE]

Clinical characteristics and prognosis of Chinese patients with hereditary transthyretin amyloid cardiomyopathy.

Orphanet J Rare Dis. 2019 11 12;14(1):251

Authors: He S, Tian Z, Guan H, Li J, Fang Q, Zhang S

Abstract
BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized progressive cardiomyopathy with heterogenous clinical manifestations that lead to its misdiagnosis and poor prognosis. This study was performed to describe the clinical characteristics and natural history of Chinese patients to improve clinical awareness of this condition.
METHODS: In this study, we retrospectively investigated 23 patients with a confirmed diagnosis of hereditary ATTR-CM in Peking Union Medical College hospital from From January 1, 2000 to December 31, 2018.
RESULTS: In all, 16 patients (69.6%) were males, the median age at disease onset was 45 (33,55) years old. The median duration from symptom onset to diagnosis was 30 (18,46) months. Phenotypes were classified as exclusively cardiac (n = 1, 4.3%) and mixed type (n = 22, 95.6%). The common mutations were Gly47Arg (7 patients [30.4%]) and Val30Ala (3 patients [13%]). Ventricular hypertrophy was observed in 23 (100%) patients, the mean thickness of the ventricular septum was 16.1 ± 3.9 mm, the mean thickness of the left ventricular posterior wall was 15.1 ± 2.8 mm. The mean left ventricle ejection fraction (LVEF) was 57.3 ± 11.9% and only 5 patients (21.7%) had LVEF < 50%. 18 (78.3%) patients had abnormal electrocardiography and the most common feature was pseudoinfarct pattern (56.5%). Overall survival at 12, 24, 36, 48, and 60 months after diagnosis was 77.8, 55.6, 38.9, 27.8, and 11.1%, respectively. Survival was better in patients with EF ≥50% than in those with EF < 50% [log Rank (Mantel-Cox), χ2 = 4.03, P = 0.045].
CONCLUSIONS: The clinical characteristics of ATTR are heterogeneous: men are more likely to be affected and onset symptoms are not obvious in the heart and mainly include peripheral neuropathy and autonomic neuropathy; however, LV hypertrophy, especially a thick ventricular septum and posterior wall with preserved LVEF, are often detected on echocardiography. Abnormal ECG manifestations are common. The prognosis is poor, and patients with EF > 50% have better survival. Clinicians should be more aware of the complex clinical profile of ATTR amyloidosis to avoid misdiagnosis in practice.

PMID: 31718691 [PubMed - indexed for MEDLINE]

Telomeropathies: Etiology, diagnosis, treatment and follow-up. Ethical and legal considerations.

Clin Genet. 2019 07;96(1):3-16

Authors: Armando RG, Mengual Gomez DL, Maggio J, Sanmartin MC, Gomez DE

Abstract
Telomeropathies involve a wide variety of infrequent genetic diseases caused by mutations in the telomerase maintenance mechanism or the DNA damage response (DDR) system. They are considered a family of rare diseases that often share causes, molecular mechanisms and symptoms. Generally, these diseases are not diagnosed until the symptoms are advanced, diminishing the survival time of patients. Although several related syndromes may still be unrecognized this work describes those that are known, highlighting that because they are rare diseases, physicians should be trained in their early diagnosis. The etiology and diagnosis are discussed for each telomeropathy and the treatments when available, along with a new classification of this group of diseases. Ethical and legal issues related to this group of diseases are also considered.

PMID: 30820928 [PubMed - indexed for MEDLINE]

[Oral markers of histiocytosis-x from Langerhans cells in a 13-year-old child].

Stomatologiia (Mosk). 2020;99(4):52-56

Authors: Sedoikin AG, Kiselnikova LP, Drobotko LN

Abstract
Langerhanscell histiocytosis is an orphan disease based on clonal proliferation of pathologic histocytes and specific infiltrates in various organs and tissues. In case of localization of pathologic foci in the sponge substances of the flat bones of the lower jaw the disease brings on morphological changes and neurological symptoms typical of dental pulp diseases. Early diagnosis of latent neoplastic processes in the TMJ area in children in the clinic allows us to minimize the volume of surgery and start the treatment of the main disease in time that improves a child's quality of life.

PMID: 32692520 [PubMed - indexed for MEDLINE]

Whole-genome sequencing of patients with rare diseases in a national health system.

Nature. 2020 07;583(7814):96-102

Authors: Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, Chinnery PF, Dixon PH, Gale DP, James R, Koziell A, Laffan MA, Levine AP, Maher ER, Markus HS, Morales J, Morrell NW, Mumford AD, Ormondroyd E, Rankin S, Rendon A, Richardson S, Roberts I, Roy NBA, Saleem MA, Smith KGC, Stark H, Tan RYY, Themistocleous AC, Thrasher AJ, Watkins H, Webster AR, Wilkins MR, Williamson C, Whitworth J, Humphray S, Bentley DR, NIHR BioResource for the 100,000 Genomes Project, Kingston N, Walker N, Bradley JR, Ashford S, Penkett CJ, Freson K, Stirrups KE, Raymond FL, Ouwehand WH

Abstract
Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

PMID: 32581362 [PubMed - indexed for MEDLINE]

Hemifacial Spasm as a Rare Clinical Presentation of Idiopathic Intracranial Hypertension: Case Report and Literature Review.

Ann Otol Rhinol Laryngol. 2020 Aug;129(8):829-832

Authors: Poff CB, Lipschitz N, Kohlberg GD, Breen JT, Samy RN

Abstract
OBJECTIVES: To report a rare case of idiopathic intracranial hypertension (IIH) presenting with hemifacial spasm (HFS) and review the current literature.
METHODS: Case report and literature review. The patient's medical record was reviewed for demographic and clinical data. For literature review, all case reports or other publications published in English literature were identified using PUBMED.
RESULTS: A 43-year-old obese female presented with a 2-year history of left HFS.Electroencephalography and head computed tomography were unremarkable. Magnetic resonance imaging demonstrated bilateral anterior inferior cerebellar artery vascular loops involving the internal auditory canals as well as IIH-associated findings. A lumbar puncture was performed and revealed an elevated opening pressure of 26 cm H20 cerebrospinal fluid. Acetazolamide treatment was then initiated, resulting in complete resolution of the HFS.
CONCLUSION: HFS may be a rare presenting manifestation of IIH, and treatment of IIH may result in improvement of HFS symptoms. This is the first report of IIH presenting with HFS in the absence of headache or visual change. As a result, this is the first report of HFS as a presenting manifestation of IIH in Otolaryngology literature.

PMID: 32390451 [PubMed - indexed for MEDLINE]

Editorial Comment.

J Urol. 2020 07;204(1):56

Authors: Shkolyar E, Mach KE, Liao JC

PMID: 32282282 [PubMed - indexed for MEDLINE]

Emphysematous osteomyelitis of the spine: A rare case report.

Medicine (Baltimore). 2020 Jul 10;99(28):e21113

Authors: Sung S, Lee BH, Kim JH, Park Y, Ha JW, Moon SH, Lee HM, Kwon JW

Abstract
RATIONALE: Emphysematous osteomyelitis is a rare disease caused by gas-forming bacteria. But only 45 cases have been reported in the literature since then.
PATIENT CONCERNS: A 72-year-old female presented to our hospital with severe lower back pain that aggravated 4 days ago.
DIAGNOSES: Computed tomography (CT) revealed intraosseous mottled air in the T12 and L1 vertebral bodies and epidural space. The enhanced T1 and T2 magnetic resonance imaging scans showed heterogeneous signal intensity of vertebral bodies, suggestive of emphysematous osteomyelitis.
INTERVENTIONS: Surgery was performed to identify culture strains and to remove emphysematous lesions of the vertebral body using extensive transpedicular irrigation.
OUTCOMES: Escherichia coli (E coli) was identified in the surgical specimen, and intravenous antibiotic therapy was continued with cefotaxime. The patient had a significant decrease in lower back pain after the surgery and the final CT scan before discharge revealed significantly decreased air at T12 and L1 vertebral bodies and no air density in the epidural space.
LESSONS: We present a patient diagnosed with emphysematous osteomyelitis in vertebral bodies caused by E coli and successfully treated with surgical intervention.

PMID: 32664134 [PubMed - indexed for MEDLINE]

Rare disorders of penile erection.

Fertil Steril. 2020 01;113(1):6-12

Authors: Burnett AL

Abstract
This literature review presents two unusual and mystifying disorders of penile erection: painful nocturnal erections, alternatively termed sleep-related painful erections, and idiopathic stuttering priapism, a variant of recurrent ischemic priapism in which no cause is discernible. The disorders are closely related although they are distinct clinically and pathologically. The main subject areas of discussion are recognition, clinical evaluation and management although current concepts surrounding their causes and mechanisms are also addressed. It is acknowledged that despite the perceived rarities of these disorders they are impactful in terms of their disease profiles and consequences. Future advances in their management will require continued development of evidence-based treatments.

PMID: 32033724 [PubMed - indexed for MEDLINE]

Introduction: Rare and unusual andrologic syndromes that clinicians should be aware of.

Fertil Steril. 2020 01;113(1):4-5

Authors: Sigman M

Abstract
There are conditions that are rare and that most providers are unaware of or conditions that consist of a series of symptoms for which there is no agreement that they are even a medical condition. These include painful nocturnal erections, post-orgasmic illness syndrome, body dysmorphic disorder, and post-finasteride syndrome. While some have a psychiatric basis, others clearly have an organic pathophysiology, while for others, there remains much controversy. This month's Views and Reviews will inform the reader of these conditions so they may recognize affected patients and direct them towards appropriate resources for their care.

PMID: 32033721 [PubMed - indexed for MEDLINE]