Familial florid osseous dysplasia: a report with review of the literature.

BMJ Case Rep. 2016 Mar 30;2016:

Authors: Kucukkurt S, Rzayev S, Baris E, Atac MS

Abstract
There are three types of osseous dysplasia: periapical cemental dysplasia (PCD), focal cemento-osseous dysplasia (FCD) and florid osseous dysplasia (FOD). While PCD is often observed in mandibular anterior teeth, FCD mainly affects mandibular posterior teeth. FOD, on the other hand, commonly involves both jaws. FOD is a type of sclerosing disease that is characterised by intense opaque masses and many areas with different densities. Genetic heritance of FOD is unusual, with only a few reported cases. We describe a case of FOD that affected three family members, discuss its clinical, radiological and histological characteristics, and review the literature.

PMID: 27030456 [PubMed - indexed for MEDLINE]

IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy.

BMJ Case Rep. 2016 Mar 23;2016:

Authors: Yamada R, Horiguchi S, Yamashita T, Kamisawa T

Abstract
IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.

PMID: 27009197 [PubMed - indexed for MEDLINE]

B-cell lymphoma of the heart: A rare diagnosis.

Rev Port Cardiol. 2014 Dec;33(12):803.e1-3

Authors: Matos AP, Palas J, Doulaptsis C, Ramalho M, Duarte S, Bogaert J

Abstract
We present a case of a primary cardiac lymphoma in a 60-year-old woman. The clinical presentation was non-specific and the diagnosis was suggested by its appearance on multidetector computed tomography. The final diagnosis was achieved by histopathological study and was corroborated by a decrease in tumor volume after targeted chemotherapy. A brief review of the appearance of primary cardiac lymphomas in imaging studies is presented.

PMID: 25459635 [PubMed - indexed for MEDLINE]

Sjögren-Larsson syndrome: a rare disease of the skin and central nervous system.

BMJ Case Rep. 2016 Apr 19;2016:10.1136/bcr-2016-215110

Authors: Roy U, Das U, Pandit A, Debnath A

Abstract
Sjögren-Larsson syndrome is a recessively inherited disease caused by a deficiency of fatty aldehyde dehydrogenase with presenting features of congenital ichthyosis, spastic diplegia or tetraplegia, and mental retardation. The basic pathogenic mechanism is deficiency of fatty aldehyde dehydrogenase, which may lead to an accumulation of long-chain fatty alcohols hampering cell membrane integrity, which further disrupts the barrier function of skin and white matter of the brain. MRI of the brain shows diffuse symmetrical white matter hyperintensities on T2-weighted sequences. Although there is no definitive cure for Sjögren-Larsson syndrome, most patients survive until adulthood and management involves therapies directed towards controlling specific problems. We present a case of Sjögren-Larsson syndrome with classical clinical and MRI features, including a few distinctly atypical characteristics in various attributes.

PMID: 27095813 [PubMed - indexed for MEDLINE]

A rare complication resulting in a rare disease: radiation-induced male breast cancer.

BMJ Case Rep. 2016 Apr 15;2016:10.1136/bcr-2015-211874

Authors: Alazhri J, Saclarides C, Avisar E

Abstract
The increase in survival after childhood radiation therapy for some blood malignancies has led to an increase in the diagnosis of radiation-induced secondary solid malignancies (SSM). We report a young man presenting with invasive breast cancer 19 years after receiving radiation therapy and bone marrow transplant for acute lymphocytic leukaemia in childhood. This latency period is longer than previously reported. Therefore, survivors of radiation-treated primary cancer should be closely monitored for SSM, including breast cancer, for the rest of their lives.

PMID: 27084898 [PubMed - indexed for MEDLINE]

Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports.

Am J Med Genet A. 2016 May;170A(5):1165-73

Authors: Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D'Angelo EJ, Yu TW, Beggs AH, Picker J, Fogler JM, Carroll D, Schmitt RC, Wolff RR, Shen Y, Lip V, Bilguvar K, Kim A, Tembulkar S, O'Donnell K, Gonzalez-Heydrich J

Abstract
Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis.

PMID: 26887912 [PubMed - indexed for MEDLINE]

[Financing rare or orphan diseases].

Rev Peru Med Exp Salud Publica. 2014 Oct-Dec;31(4):808-9

Authors: Oyola-García A, Lituma-Aguirre D, Honorio-Morales H, Comisión Sectorial Enfermedades Raras o Huérfanas

PMID: 25597742 [PubMed - indexed for MEDLINE]

Once again, rare diseases provide a spotlight.

Mol Genet Metab. 2016 May;118(1):1-2

Authors: Lal TR, Borger DK, Sidransky E

PMID: 27017192 [PubMed - indexed for MEDLINE]

Fibrodysplasia Ossificans Progressiva.

J Coll Physicians Surg Pak. 2016 Feb;26(2):154-5

Authors: Rashid U, Bari A, Maqsood A, Naz S, Ahmad TM

Abstract
Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disorder characterized by postnatal progressive heterotopic ossification of connective tissue and congenital malformation of big toes. We report a 3-year male toddler with clinical and radiological features of FOP. He was born with bilateral hallux valgus and at the age of 3 years presented with hard swellings over back, scapular region and forehead that were initially inflammatory and then became bony hard. There is also tilting of neck towards the left due to calcification in neck region. The radiographs showed heterotopic ossification in thoracic region, neck, spine and region of hip joint.

PMID: 26876407 [PubMed - indexed for MEDLINE]

Atypical proliferative endometrioid tumor of ovary: Report of a rare case.

J Postgrad Med. 2016 Apr-Jun;62(2):129-32

Authors: Jetley S, Khetrapal S, Ahmad A, Jairajpuri ZS

Abstract
Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence.

PMID: 26497398 [PubMed - indexed for MEDLINE]

Living with and treating rare diseases: experiences of patients and professional health care providers.

Qual Health Res. 2015 May;25(5):636-51

Authors: Garrino L, Picco E, Finiguerra I, Rossi D, Simone P, Roccatello D

Abstract
We explored the experiences of illness of patients suffering from rare diseases and of the health professionals who care for them at the Center for the Interregional Coordination of Rare Diseases of Piedmont and Valle d'Aosta in Italy. The research was carried out between 2010 and 2011. We collected qualitative data from 22 patients and 12 health professional health care providers. The interviews were analyzed using the Colaizzi phenomenological approach. We identified five themes from the narratives of the patient participants--dealing with disease development, living with the disease, everyday living, relating to others, and relations with health care providers--and four themes from the professional health care participants--dealing with the disease, dealing with expectations, building relationships, and being operators in the context. The study has raised awareness about the issue of rare diseases and it provides some useful considerations for improving services.

PMID: 25667160 [PubMed - indexed for MEDLINE]

Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex.

Cell. 2016 Aug 25;166(5):1147-1162.e15

Authors: Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA

Abstract
Alternative splicing is prevalent in the mammalian brain. To interrogate the functional role of alternative splicing in neural development, we analyzed purified neural progenitor cells (NPCs) and neurons from developing cerebral cortices, revealing hundreds of differentially spliced exons that preferentially alter key protein domains-especially in cytoskeletal proteins-and can harbor disease-causing mutations. We show that Ptbp1 and Rbfox proteins antagonistically govern the NPC-to-neuron transition by regulating neuron-specific exons. Whereas Ptbp1 maintains apical progenitors partly through suppressing a poison exon of Flna in NPCs, Rbfox proteins promote neuronal differentiation by switching Ninein from a centrosomal splice form in NPCs to a non-centrosomal isoform in neurons. We further uncover an intronic human mutation within a PTBP1-binding site that disrupts normal skipping of the FLNA poison exon in NPCs and causes a brain-specific malformation. Our study indicates that dynamic control of alternative splicing governs cell fate in cerebral cortical development.

PMID: 27565344 [PubMed - indexed for MEDLINE]

Often seen, rarely recognized: mast cell activation disease--a guide to diagnosis and therapeutic options.

Ann Med. 2016;48(3):190-201

Authors: Afrin LB, Butterfield JH, Raithel M, Molderings GJ

Abstract
Mast cell (MC) disease has long been thought to be just the rare disease of mastocytosis (in various forms, principally cutaneous and systemic), with aberrant MC mediator release at symptomatic levels due to neoplastic MC proliferation. Recent discoveries now show a new view is in order, with mastocytosis capping a metaphorical iceberg now called "MC activation disease" (MCAD, i.e. disease principally manifesting inappropriate MC activation), with the bulk of the iceberg being the recently recognized "MC activation syndrome" (MCAS), featuring inappropriate MC activation to symptomatic levels with little to no inappropriate MC proliferation. Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD's clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory ± allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS. We review the diagnostically challenging presentation of MCAD (with an emphasis on MCAS) and current thoughts regarding its biology, epidemiology, natural history, diagnostic evaluation, and treatment.

PMID: 27012973 [PubMed - indexed for MEDLINE]

Liver transplantation for adenomatosis: European experience.

Liver Transpl. 2016 Apr;22(4):516-26

Authors: Chiche L, David A, Adam R, Oliverius MM, Klempnauer J, Vibert E, Colledan M, Lerut J, Mazzafero VV, Di-Sandro S, Laurent C, Scuderi V, Suc B, Troisi R, Bachelier P, Dumortier J, Gugenheim J, Mabrut JY, Gonzalez-Pinto I, Pruvot FR, Le-Treut YP, Navarro F, Ortiz-de-Urbina J, Salamé E, Spada M, Bioulac-Sage P

Abstract
The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

PMID: 26919265 [PubMed - indexed for MEDLINE]

The changing face of liver transplantation for acute liver failure: Assessment of current status and implications for future practice.

Liver Transpl. 2016 Apr;22(4):527-35

Authors: Donnelly MC, Hayes PC, Simpson KJ

Abstract
The etiology and outcomes of acute liver failure (ALF) have changed since the definition of this disease entity in the 1970s. In particular, the role of emergency liver transplantation has evolved over time, with the development of prognostic scoring systems to facilitate listing of appropriate patients, and a better understanding of transplant benefit in patients with ALF. This review examines the changing etiology of ALF, transplant benefit, outcomes following transplantation, and future alternatives to emergency liver transplantation in this devastating condition.

PMID: 26823231 [PubMed - indexed for MEDLINE]

Coronary artery disease in Eisenmenger's syndrome--Rare but not to be forgotten.

Int J Cardiol. 2016 Jan 15;203:276-7

Authors: Abraham D, Freeman LJ, Lewis C, O'Sullivan M

PMID: 26519685 [PubMed - indexed for MEDLINE]

Putative modifier genes in mevalonate kinase deficiency.

Mol Med Rep. 2016 Apr;13(4):3181-9

Authors: Marcuzzi A, Vozzi D, Girardelli M, Tricarico PM, Knowles A, Crovella S, Vuch J, Tommasini A, Piscianz E, Bianco AM

Abstract
Mevalonate kinase deficiency (MKD) is an autosomal recessive auto‑inflammatory disease, caused by impairment of the mevalonate pathway. Although the molecular mechanism remains to be elucidated, there is clinical evidence suggesting that other regulatory genes may be involved in determining the phenotype. The identification of novel target genes may explain non‑homogeneous genotype‑phenotype correlations, and provide evidence in support of the hypothesis that novel regulatory genes predispose or amplify deregulation of the mevalonate pathway in this orphan disease. In the present study, DNA samples were obtained from five patients with MKD, which were then analyzed using whole exome sequencing. A missense variation in the PEX11γ gene was observed in homozygosis in P2, possibly correlating with visual blurring. The UNG rare gene variant was detected in homozygosis in P5, without correlating with a specific clinical phenotype. A number of other variants were found in the five analyzed DNA samples from the MKD patients, however no correlation with the phenotype was established. The results of the presents study suggested that further analysis, using next generation sequencing approaches, is required on a larger sample size of patients with MKD, who share the same MVK mutations and exhibit 'extreme' clinical phenotypes. As MVK mutations may be associated with MKD, the identification of specific modifier genes may assist in providing an earlier diagnosis.

PMID: 26935981 [PubMed - indexed for MEDLINE]

Socio-economic burden of rare diseases: A systematic review of cost of illness evidence.

Health Policy. 2015 Jul;119(7):964-79

Authors: Angelis A, Tordrup D, Kanavos P

Abstract
Cost-of-illness studies, the systematic quantification of the economic burden of diseases on the individual and on society, help illustrate direct budgetary consequences of diseases in the health system and indirect costs associated with patient or carer productivity losses. In the context of the BURQOL-RD project ("Social Economic Burden and Health-Related Quality of Life in patients with Rare Diseases in Europe") we studied the evidence on direct and indirect costs for 10 rare diseases (Cystic Fibrosis [CF], Duchenne Muscular Dystrophy [DMD], Fragile X Syndrome [FXS], Haemophilia, Juvenile Idiopathic Arthritis [JIA], Mucopolysaccharidosis [MPS], Scleroderma [SCL], Prader-Willi Syndrome [PWS], Histiocytosis [HIS] and Epidermolysis Bullosa [EB]). A systematic literature review of cost of illness studies was conducted using a keyword strategy in combination with the names of the 10 selected rare diseases. Available disease prevalence in Europe was found to range between 1 and 2 per 100,000 population (PWS, a sub-type of Histiocytosis, and EB) up to 42 per 100,000 population (Scleroderma). Overall, cost evidence on rare diseases appears to be very scarce (a total of 77 studies were identified across all diseases), with CF (n=29) and Haemophilia (n=22) being relatively well studied, compared to the other conditions, where very limited cost of illness information was available. In terms of data availability, total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five diseases. Overall, data availability was found to correlate with the existence of a pharmaceutical treatment and indirect costs tended to account for a significant proportion of total costs. Although methodological variations prevent any detailed comparison between conditions and based on the evidence available, most of the rare diseases examined are associated with significant economic burden, both direct and indirect.

PMID: 25661982 [PubMed - indexed for MEDLINE]

[Ophthalmogenetics: Rare Diseases - A Challenge for Diagnostic and Treatment].

Klin Monbl Augenheilkd. 2016 Mar;232(3):242

Authors: Rudolph G

PMID: 27011027 [PubMed - indexed for MEDLINE]

GerOSS (German Obstetric Surveillance System). A Project to Improve the Treatment of Obstetric Rare Diseases and Complications Using a Web Based Documentation and Information Platform.

Methods Inf Med. 2015;54(5):406-11

Authors: Berlage S, Grüßner S, Lack N, Franz HB

Abstract
BACKGROUND: Severe and very rare obstetric complications (e.g. eclampsia, postpartum haemorrhage or uterine rupture), typically culminate in a chaotic, uncontrollable sequence of events. Outcome for mother and child depends on whether doctors and midwives are able to quickly take correct decisions and initiate optimal treatment.
OBJECTIVES: GerOSS (German Obstetric Surveillance System) aims at generating deeper insight into relevant risk factors to improve diagnosis and treatment of severe complications during pregnancy and delivery. As such it is primarily conceived as a system for quality improvement and less as a register. Another focus is the provision of an information and communication platform for dissemination of these insights. Finally, incidences of selected rare obstetric events may be derived.
METHODS: These rare events are monitored for two to five years in Lower Saxony, Bavaria and Berlin. Quantitative analyses of aggregate data are complemented with in depth case based anonymised evaluations by experts. The temporal sequence of measures taken as well as the management of care is inspected. Participants receive a feedback of comments on the synopsis of individual cases. Aggregate data results are published and made available through the GerOSS platform. A scientific advisory committee ensures the link with the professional scientific bodies. A comparison within INOSS (International Network of Obstetric Survey Systems) allows additional insights into the treatment of obstetric rare diseases and complications. More reliable estimates of the incidence of such events can be computed and compared within a larger database.
RESULTS: Following the implementation in three federal states in Germany in 2010, participation in GerOSS-Project has increased to 100% of all hospitals with a delivery unit in Lower Saxony, 30% in Bavaria and 80% in Berlin. Feasibility of the project is shown by successful implementation of GerOSS. Quantitative analyses enable construction of risk profiles (e.g. for the prevalence of hysterectomies and uterine ruptures) such that tailored treatment algorithms may be derived. Age, body mass index and previous caesarean section are common risk factors when complications occur. Respective recommendations have not always been adhered to in the diagnosis and therapy of such cases. The presentation of initial GerOSS results has paved the path for first changes in obstetric care.
CONCLUSIONS: The envisaged expansion of GerOSS to an interactive platform will allow dissemination of insights such that optimal obstetric care and transferal among all involved medical facilities may see future enhancements via the internet or even through smartphone applications.

PMID: 26065375 [PubMed - indexed for MEDLINE]