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Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.

A 61-year-old gentleman presented with small bowel intussusception from small bowel melanoma intussusceptum. He complains of intermittent abdominal distension but no history of intestinal obstruction. Apart from this, he was also symptomatic anemia which required repeated transfusion for the past few months. The contrast-enhanced computed tomography of the abdomen shows an omental mass with small bowel intussusception. He then underwent an exploratory laparotomy with segmental resection of the affected segment. Histopathological examination confirmed primary gastrointestinal melanoma. Multiple small bowel malignant melanoma is a rare disease. It remains a controversial diagnosis as it may be a primary or metastasis from an unidentified or regressed primary cutaneous melanoma. Prompt surgical intervention enables us to obtain tissue diagnosis, prevent complete intestinal obstruction and strategize the goals of treatment for the patient.

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare disease with a poor prognosis. Because of its rarity, there is no established therapeutic regimen in unresectable cases. We report a case of PSCCT treated with weekly paclitaxel (wPTX) for more than 2 years. A 59-year-old woman presented to our hospital with a progressively enlarging neck mass. CT and MRI scans showed a tumor arising from the right lobe of the thyroid, invading the esophagus and trachea, as well as partially surrounding and invading the right common carotid artery. It was deemed unresectable. Biopsy revealed poorly differentiated squamous cell carcinoma. wPTX therapy was initiated. The patient achieved a partial response and is still undergoing treatment 28 months later. Adverse events included grade 3 neutropenia and grade 2 peripheral sensory neuropathy, which were manageable. Long-term wPTX therapy has been effective in this case of unresectable PSCCT.

Odontochondrodysplasia (ODCD, OMIM #184260) is a quite rare non-lethal skeletal dysplasia characterized by involvement of the spine and metaphyseal regions of the long bones, pulmonary hypoplasia, short stature, joint hypermobility, and dentinogenesis imperfecta. ODCD is inherited in an autosomal recessive fashion with an unknown frequency caused by mutations of the thyroid hormone receptor interactor 11 gene (TRIP11; OMIM *604505). TRIP11 gene encodes the Golgi microtubule-associated protein 210 (GMAP-210), which is an indispensable protein for the function of the Golgi apparatus. Mutations of the TRIP11 gene also cause achondrogenesis type 1A (ACG1A). Null mutations of TRIP11 lead to ACG1A, also known as a lethal skeletal dysplasia, while hypomorphic mutations cause ODCD. Here we report a male child diagnosed as ODCD with a novel compound heterozygote mutation who presented with skeletal changes, short stature, dentinogenesis imperfecta, and facial dysmorphism resembling Achondroplasia (ACH) and Hypochondroplasia (HCH).

© 2022-IOS Press. All rights reserved.Sjögren-Larsson syndrome (SLS) is a rare neurocutaneous disorder characterized by the presence of congenital ichthyosis, spasticity, and mental retardation. As with other rare genetic diseases, treatment is mainly symptomatic. Due to the absence of definitive treatment, lifelong follow-up and support of patients are important to improve the quality of life. A 7-year-old female child who was diagnosed as having SLS was referred to the rehabilitation clinic. After 20 sessions of a rehabilitation program, she started walking independently with the additional contribution of ankle-foot orthoses (AFOs). The contribution of the short-term rehabilitation approach and especially the administration of AFOs to the independence level of the patient is emphasized herein.

Background: Some reports have described intraosseous arteriovenous fistulas showing osteolytic changes, but an osseous arteriovenous fistula (AVF) at the jugular bulb showing extensive bone destruction is a very rare disease. Case description: A 60-year-old man presented with pulsatile tinnitus and right facial nerve palsy. Radiological imaging showed a large homogenously enhanced osteolytic lesion at the right jugular foramen. A cerebral angiogram showed a high-flow vascular lesion of the jugular bulb associated with retrograde sinus reflux, resulting in venous congestion of the deep venous system. These findings led us to misdiagnose this lesion as a glomus jugular tumor. However, combined arterial and venous angiography after transarterial embolization revealed the precise angioarchitecture, and we finally diagnosed this lesion as a high-flow osseous AVF at the jugular bulb. We performed transvenous embolization using a triple catheter technique. The lesion was successfully obliterated, and the 6-months angiogram showed no recurrence. Conclusion: A rare case of high flow osseous AVF at the jugular bulb associated with osteolytic changes in the surrounding bony structure is reported. Although many hypervascular lesions at the jugular bulb are glomus tumors, bone destructive osseous AVF at the jugular bulb should be considered.

TAFRO syndrome is a very rare disease, with less than 100 cases reported in the literature. It is classified as a type of idiopathic multicentric Castleman disease, but it has clinical, paraclinical, and histopathological characteristics that differentiate between TAFRO and idiopathic forms of Castleman disease not otherwise specified. However, it is a challenging exclusion diagnosis. TAFRO syndrome is characterized by systemic inflammatory involvement, often severe, which can present with kidney failure, and become a severe disease with a high mortality rate. The clinical manifestations of TAFRO can be confused with hematology malignancies or various autoimmune diseases. Although there are some reports of TAFRO syndrome associated with autoimmune compromise, there is no published consensus for the diagnosis or treatment. The case presented is a patient who meets the criteria to be classified as SLE, and with manifestations with significant clinical involvement, but with no improvement with standard treatment. It was found that the patient's systemic involvement was due to TAFRO, and that therefore the TAFRO syndrome could simulate SLE, something previously not described in the literature.

Introduction Hemophagocytic lymphohistiocytosis comprises a systemic hyperactivation of macrophages that requires prompt recognition of symptoms and early treatment. Objective and Method In this context, we described clinical and laboratory characteristics, therapeutic modality and outcome of 21 patients with HLH treated at a pediatric oncology hospital between January 2000 and February 2019. Results HLH mainly affected females, fever was the most frequent clinical sign and hyperferritinemia was the most prevalent laboratory abnormality. All patients were admitted to the intensive care unit (ICU) at some point. Fifteen (71.4%) patients presented resolution criteria and eight (53.3%) of them presented reactivation. The mortality rate was 57.1% and the mean time between diagnosis and death was 9.98 months. The 5-year overall survival (OS) was 36.7%. We observed a significant difference in prognosis associated with reactivation of HLH. These patients demonstrated an estimated 5-year OS of 25%, while all patients that did not reactivate were alive until the end of the follow-up. Conclusion In conclusion, HLH is a rare disease with a high mortality rate, especially in patients with disease reactivation and those with familial- or immunodeficiency-associated forms, which makes early recognition and genetic testing crucial for appropriate management and prompt SCT indication.

Pure red cell aplasia is a relatively rare disease characterized by suppression or absence of erythroid precursors while other cell lineages are normal in the bone marrow. The disease could be secondary to other diseases or an adverse side effect of certain drugs. Tacrolimus is widely used as an immunosuppressive agent in solid-organ transplant without significant myelosuppressive effects. However, several tacrolimus-related pure red cell aplasia cases have been reported to date. Here, we report a case of a renal transplant recipient who developed tacrolimus-associated pure red cell aplasia in the posttransplant period and recovered dramatically after switching from tacrolimus to cyclosporine. Early diagnosis of pure red cell aplasia, which generally requires multiple blood transfusions, is very important because an increased number of blood transfusions can cause immunogenic effects and increased risk for allograft survival. Tacrolimus is a prominent drug for immunosuppression and is suspected to cause pure red cell aplasia during the posttransplant period; therefore, clinicians should consider a switch from tacrolimus to another immunosuppressive agent.

To present a case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome that was successfully managed with serial intravitreal aflibercept injections.Ophthalmic imaging and visual acuity were used to monitor disease state and track treatment methods to determine the most valuable combination of treatment medication and treatment interval.A 28-year-old woman with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome status after panretinal photocoagulation of both eyes presented with bilateral cystoid macular edema. We demonstrate successful management of retinal cystoid macular edema associated with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome using serial intravitreal aflibercept injections.Intravitreal aflibercept has a useful role in managing the potential retinal complications associated with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome and provides further insights into treatment of the later stages of this rare disease.

Dyskeratosis congenita is a rare disease caused by telomerase dysfunction classically characterised by the triad: skin pigmentation, nail dystrophy and mucosal leukoplakia. Few cases are described in literature regarding patients with head and neck squamous cell carcinoma affected by dyskeratosis congenita, and the therapeutic decisions are not yet well defined. A review of the literature of the last 20 years (2001–2021) was performed, and it was analysed the case of a 38-year-old male patient affected by dyskeratosis congenita diagnosed with a squamous cell carcinoma of the inferior alveolar ridge, treated with surgery. The absence of complications and the good postoperative recovery of the patient comfort in saying that resection and reconstructive surgery can be safely performed. The occurrence of disseminated disease 6 months after the treatment warns about the extreme aggressiveness of the pathology, its often systemic nature and the necessity of a multidisciplinary approach as well as further studies.

Background Next-generation sequencing (NGS) based population screening holds great promise for disease prevention and earlier diagnosis, but the costs associated with screening millions of humans remain prohibitive. New methods for population genetic testing that lower the costs of NGS without compromising diagnostic power are needed. Methods We developed double batched sequencing where DNA samples are batch-sequenced twice — directly pinpointing individuals with rare variants. We sequenced batches of at-birth blood spot DNA using a commercial 113-gene panel in an explorative (n = 100) and a validation (n = 100) cohort of children who went on to develop pediatric cancers. All results were benchmarked against individual whole genome sequencing data. Results We demonstrated fully replicable detection of cancer-causing germline variants, with positive and negative predictive values of 100% (95% CI, 0.91–1.00 and 95% CI, 0.98–1.00, respectively). Pathogenic and clinically actionable variants were detected in RB1, TP53, BRCA2, APC, and 19 other genes. Analyses of larger batches indicated that our approach is highly scalable, yielding more than 95% cost reduction or less than 3 cents per gene screened for rare disease-causing mutations. We also show that double batched sequencing could cost-effectively prevent childhood cancer deaths through broad genomic testing. Conclusions Our ultracheap genetic diagnostic method, which uses existing sequencing hardware and standard newborn blood spots, should readily open up opportunities for population-wide risk stratification using genetic screening across many fields of clinical genetics and genomics.

Progressive familial intrahepatic cholestasis (PFIC) is a rare disease of impaired bile acid excretion which can lead to nutritional deficiencies. Vitamin deficiencies during pregnancy can result in adverse maternal and fetal outcomes. A 20-year-old primiparous woman at 30 4/7 weeks with PFIC type 2 presented with worsening cholestasis, coagulopathy and fat-soluble vitamin deficiency. She developed visual deficits and was found to have severe vitamin A deficiency. Her coagulopathy and visual deficits improved following vitamin K and A supplementation, respectively. She delivered at 32 2/7 weeks following preterm labour. This case highlights several unique aspects in the care of pregnant women with liver disease. These patients are at risk for fat-soluble vitamin deficiencies which can result in significant coagulopathy and rarely, visual deficits due to vitamin A deficiency. Prompt treatment is necessary to prevent permanent sequelae.

A 75-year-old man was referred to our urology service with painless haematuria. The delayed phase on a subsequent computed tomography (CT) abdomen and pelvis showed a filling defect in the left renal pelvicalyceal system, suspicious for a transitional cell carcinoma. The patient underwent ureteroscopic biopsy suggestive of a papillary neoplasia, before progressing to a laparoscopic radical left nephrouretectomy. Final histology revealed a fumarate hydratase-deficient renal cell carcinoma with clear margins. The patient was subsequently referred for genetic counselling.

Colonic diffuse ganglioneuromatosis is an extremely rare disease in which multiple tumors derived from the ganglion cells, nerve fibers, and supporting cells are distributed in the colon. It is generally considered to be a benign neoplastic condition and is occasionally associated with rare hereditary conditions such as neurofibromatosis type I or multiple endocrine neoplasia type 2B. Here, we report a case of a patient in whom colon cancer developed 12 years after the initial diagnosis of colonic diffuse ganglioneuromatosis, which suggests a possible association between colonic diffuse ganglioneuromatosis and colorectal cancer.

The communication of genomic results to patients and families with rare diseases raise distinctive challenges. However, there is little evidence about optimal methods to communicate results to this group of service users. To address this gap, we worked with rare disease families and health professionals from two genetic/genomic services, one in the United Kingdom and one in the Czech Republic, to co-design that best meet their needs. Using the participatory methodology of Experience-Based Co-Design (EBCD), we conducted observations of clinical appointments (n=49) and interviews with family participants (n=23) and health professionals (n=22) to gather their experience of sharing/receiving results. The findings informed a facilitated co-design process, comprising 3 feedback events at each site and a series of meetings and remote consultations. Participants identified a total of four areas of current service models in need of improvement, and co-designed six prototypes of quality improvement interventions. The main finding was the identification of post-test care as the shared priority for improvement for both health professionals and families at the two sites. Our findings indicate the need to strengthen the link between diagnostics (whether or not a pathogenic variant is found) and post-test care, including psychosocial and community support. This raises implications for the reconfigurations of genomic service models, the redefinition of professional roles and responsibilities and the involvement of rare disease patients and families in health care research.

Nodal marginal zone lymphoma (NMZL) is a type of low-grade B-cell lymphoma arising in the follicular marginal zone of the lymph nodes. It is an extremely rare disease that accounts for 1.5 %–1.8 % of all malignant lymphomas. We herein report a case of nodal marginal zone lymphoma arising in the submental region. A 45-year-old woman was referred to our hospital because of swelling of the submental region. Contrast-enhanced computed tomography revealed 2 masses measuring 25 and 10 mm in diameter in the submental region, and the inside of the masses showed uniform enhancement. Magnetic resonance imaging revealed a low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted images. Given these findings, the clinical diagnosis was submental tumor. We performed lymphadenectomy under general anesthesia. The histopathological diagnosis was NMZL. Subsequently, the patient was referred to the Department of Hematology, and a general examination was performed. There were no B symptoms, such as a fever or weight loss, and no lesions were found at other sites. The patient was ultimately diagnosed with Stage IA disease by Ann Arbor staging. At present, 26 months have passed, and the postoperative course has been uneventful.

Primary pulmonary artery (PA) sarcoma (PAS) is a rare disease with poor prognosis. Radical resection provides the best curative chances. Our 60-year old male patient underwent PAS excision with pericardial patch repair of the main PA in 2017, but required reoperation in 2019 due to recurrence. Total PA bifurcation replacement was performed using a handmade two-limbed bovine pericardial tube graft, which has not previously been described in the literature. This technique is safe and reproducible, and may offer a valuable alternative surgical strategy for this patient cohort. Our patient is still alive four years after initial presentation.

Thoracic ossification of the posterior longitudinal ligament (T-OPLL) is a rare disease, which can cause spinal cord compression leading to various neurological symptoms. There are limited treatment options for T-OPLL, surgery is generally considered the only effective treatment. However, few studies have investigated surgical complications in patients with T-OPLL, and there are no data regarding surgical risks in anterior decompression with fusion (ADF) when compared with posterior decompression with fusion (PDF) for T-OPLL.Patients who were diagnosed as T-OPLL and underwent ADF via the anterior approach and PDF via the posterior approach from April 1, 2012 to March 31, 2018, were extracted from the Diagnosis Procedure Combination (DPC) database. We analyzed perioperative systemic and local complication rates after ADF and PDF and compared them using propensity score matching (PSM) method. In each of the two groups, we investigated the details of length of stay, costs, mortality, and discharge destination.In total 1344 patients (ADF: 88 patients, PDF: 1256 patients), 176 patients were investigated after PSM (88 pairs). While the incidence of overall systemic complication was significantly higher in the ADF group (ADF/PDF: 25.0%/8.0%, P = 0.002), there was no significant difference in the overall local complication rate (15.9%/19.3%, P = 0.55). Specifically, respiratory complications were more frequently observed in the ADF group (9.1%/0%, P = 0.004), however, other systemic and local complications did not differ significantly between the two groups. The length of stay was 1.7 times longer (P 0.001) and the medical costs were 1.4 times higher (P 0.001) in patients with perioperative complications, compared to those without perioperative complications.We demonstrated the perioperative complications of ADF and PDF in patients with T-OPLL using a large national database. ADF showed a higher incidence of respiratory complications. Development of perioperative complications was associated with longer hospital stay and higher medical costs.

Epstein syndrome is a rare disease characterized by macrothrombocytopenia, nephritis and progressive sensorineural hearing loss (SNHL). This syndrome is presently recognized as an autosomal dominant disease caused by mutations of non-muscle myosin heavy chain 9 (MYH9). Little information is available about the progress of SNHL, the efficacy of cochlear implants (CI) or the perioperative management of thrombocytopenia in patients with Epstein syndrome. We herein report a case of a patient with Epstein syndrome with the MYH9:c.2105G>A:p.R702H variant who underwent cochlear implantation after 27 years of follow-up for her progressive SNHL. The deterioration rates of hearing were 3.48 dB/year on the right ear and 2.46 dB/year on the left ear. The patient derived benefits from CI and had a speech recognition test result (for sentences) of 93% at 6-months postoperatively. Thrombocytopenia was successfully managed without any bleeding complications by using eltrombopag, an oral thrombopoietic agent, making transfusion of platelets unnecessary. The accurate diagnosis of Epstein syndrome was made only after long-term follow-up as the thrombocytopenia was initially diagnosed as idiopathic thrombocytopenic purpura. This case report highlights the perioperative management of thrombocytopenia, the progress of SNHL and the potential pitfalls of diagnosis.

Complex diseases, including ageing, often exhibit sexual dimorphism. These sex differences can obfuscate attribution to causal genes within a target ID campaign. Mendelian randomisation (MR)-inspired analysis provides a natural setting to incorporate X-linked aneuploid populations, resulting in prioritisation of longevity-enhancing drug targets and motivating greater inclusion of said populations in future profiling studies.

Vasculitis affecting the nervous system is a rare disease that can not only present with nonspecific initial symptoms, but also run a severe course without accurate treatment. Although improvements have been achieved, diagnosis of vasculitis remains challenging, because many classification criteria are unspecific or inconclusive with regard to central nervous system (CNS) manifestations. Currently, beside an isolated primary CNS vasculitis, several systemic types of vasculitis are known to affect the nervous system. In this review, we provide an overview of the pathophysiology, current therapeutic guidelines, and highlight novel treatment strategies for CNS vasculitis.

Background: Kimura disease is a rare inflammatory condition classically manifested as painless subcutaneous nodules in the head and neck region and associated with regional cervical lymphadenopathy and salivary gland involvement. Objective: The purpose of this report is to illustrate the diagnostic difficulty due to its rarity and non-specific clinical presentation. Case Presentation: We present a case of Kimura disease with bilateral eyelid swelling, parotid involvement, and cervical lymphadenopathy in a young boy. Computed Tomography (CT) showed ill- defined enhancing masses in both upper eyelids with lacrimal gland infiltration, multiple nodular lesions in both parotid glands, and bilateral enlargement of cervical nodes. After several multidisciplinary discussions and trials of medications, Kimura's disease was finally confirmed by histology examination. Conclusion: In conclusion, a rare disease such as Kimura must be considered earlier if the patient is not responding to the treatment.

Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.

Cushing syndrome (CS) is a rare disease caused by hypercortisolemia. Although surgical treatment is the first-line treatment in CS, the appropriate medication for the patient’s condition should be selected when medical treatment is needed. Etomidate is an adrenal-blocking drug used to treat CS and the most suitable for severe hypercortisolemia and adrenocortical carcinoma (ACC), due to cardiovascular stability and an anti-tumorigenic effect. However, its use and safe recommended dosage in infants with CS is unreported. Here we describe the case of a 2-month-old girl treated with etomidate for CS caused by ACC. Even though radical mass excision was performed, severe hypercortisolemia persisted, resulting from metastatic lesions in the liver, and medical treatment was considered. The etomidate doses, no bolus dose and infusion rate of 0.03 mg/kg/hour, may be an appropriate dose for severe hypercortisolemia in infants. This case will help determine future treatment strategies for similar cases in infants.

Background and objective Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. Material and methods Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. Results A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. Conclusions ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Objective Tuberculous otitis media (TB OM) is a rare disease. We present here our experience of TB OM on its clinical presentation, investigation and treatment outcome. Methods A retrospective observational study was performed and clinical data of patients in whom TB OM was diagnosed at our center between 2008 and 2019 was analyzed. Results Five cases of TB OM were identified. Otorrhoea was the most consistent presenting chief complaint while one of the cases presented with right post-auricular swelling. All the cases were successfully treated with anti-tuberculous medication with outcome of dry middle ear but only one case achieved full recovery of hearing loss. Conclusion Due to the disparity of presentations in all our patients, we would like to emphasize the high index of suspicion of TB OM in acute or chronic cases of otitis media with unusual presentation or poor response to standard treatment.

Characterized by small, highly heterogeneous patient populations, rare disease trials magnify the challenges often encountered in traditional clinical trials. In recent years, there have been increased efforts by stakeholders to improve drug development in rare diseases through novel approaches to clinical trial designs and statistical analyses. We highlight and discuss some of the current and emerging approaches aimed at overcoming challenges in rare disease clinical trials, with a focus on the ultimate stakeholder, the patient.

Primary spinal cord melanoma is a rare disease that accounts for only 1% of all melanocytomas. Here we report a case of primary melanoma of the cervical spinal cord. In our case, 26-year-old female who were admitted to the hospital for left arm pain. Spinal magnetic resonance image (MRI) revealed a spinal cord tumor at the level of C2-3. The MRI images showed that the tumor compressed the spinal cord. At surgery, the spinal cord was under pressure and covered with shaped blackish brown neoplastic tissue. There were not any metastatic lesions. The patient is still alive six months after surgery. 33581992

Kartagener syndrome (KS) is a rare disease with an incidence of 1 in 20,000 to 30,000 births. There is no cure for KS, and conservative medical treatments are used to relieve symptoms and prevent disease progression. Lung transplantation (LT) is the only treatment option for end-stage KS. Since patients with KS have anatomical abnormalities such as situs inversus totalis, which often require surgery to correct, most reports are related to surgical techniques. Reports about morphological adaptations and changes in transplanted lung structure after LT in patients with KS are rare. We performed LT in a patient with KS and observed morphological adaptation of the lungs for 6 months on chest computed tomography using a quantitative evaluation tool (Chest Image Platform; Harvard University Disability Resources, Cambridge, MA, USA).

Background and Purpose Cardiac myxoma is a very rare disease for which resection is the treatment gold standard. There are many neurologic manifestations associated with this disease, including embolic infarctions, arterial aneurysms, and brain metastatic myxomas, but few large-scale studies have addressed this. We here retrospectively analyzed the incidence, type, and prognosis of these neurologic disorders. Methods We enrolled 317 patients who received a cardiac myxoma resection between 2004 and 2019 at our institution. A retrospective review of the medical records and radiologic imaging was performed for each patient, and various clinical factors were compared and analyzed with regard to clinical outcomes and the incidence of adverse events. Results Patients with a neurologic disorder before surgery were found to be more likely to develop new postoperative neurologic complications (p = .003). Patients with neurologic disorder arising at any time before or after surgery had poorer outcomes (p Conclusion The clinical management of cardiac myxoma must take account of neurologic sequelae independently of the surgical intervention to remove the lesion. Cardiac myxoma patients with any neurologic disorder should undergo both neurosurgical follow-up as well as cardiac surgical follow-up, even if myxoma removal surgery has been performed. We suggest that that active neuroimaging during long term follow-up is essential in these cases.

Pulmonary arterial hypertension is a rare disease characterized by pulmonary microvasculature remodeling leading to right ventricular failure and death. Medical management of pulmonary hypertension has grown increasingly complex as more therapeutic agents have been developed. Evolving treatment strategies leveraging the endothelin, nitric oxide, and prostacyclin pathways lead to improved exercise capacity and outcomes in patients; however, significant opportunities for advancement remain.

Introduction The impact of SARS-CoV-2 in rare disease populations has been underreported. Gaucher disease (GD) is a prototype rare disease that shares with SARS-CoV-2 a disruption of the lysosomal pathway. Materials-methods Retrospective analysis of 11 patients with Type 1 GD who developed COVID-19 between March 2020 and March 2021. Results Seven male and 4 female patients with Type 1 GD developed COVID-19. One was a pediatric patient (8 years old) while the remainder were adults, median age of 44 years old (range 21 to 64 years old). Two patients required hospitalization though none required intensive care or intubation. All 11 patients recovered from COVID-19 and there were no reported deaths. Conclusions Our case series suggests that GD patients acquired COVID-19 at a similar frequency as the general population, though experienced a milder overall course despite harboring underlying immune system dysfunction and other known co-morbidities that confer high risk of adverse outcomes from SARS-CoV-2 infection.

Pulmonary alveolar proteinosis is a rare disease characterized by progressive accumulation of lipoprotein material in the alveoli as a result of a dysfunction in surfactant clearance. The whole-lung lavage procedure is considered the current standard of care and consists of the sequential lavage of both lungs for mechanical removal of residual material in the alveoli. However, a lack of standardization has resulted in different procedural techniques among institutions. Even though whole-lung lavage is considered to be a safe procedure, unforeseen complications might occur, and proper knowledge of physiologic implications may allow clinicians to establish the appropriate therapy. This review provides an insight into the underlying physiology of the disease, the technical details of the procedure from an anesthesiologist's perspective, and discussion of potential intraoperative complications.

Pediatric pulmonary hypertension (PH) is a rare disease with historically very high morbidity and mortality. In the past 20 years, there has been a growing recognition that pediatric PH, although having similarities to adult PH, is a unique entity with its own particular pathogeneses, presentation, and management. With better understanding and earlier diagnosis of pediatric PH, and as more medications have become available, survival of children with PH has also significantly improved. This article reviews the various forms of PH in childhood, with a focus on both established and investigational therapies that are available for children with PH.

Pleuropulmonary blastomas are rare, potentially aggressive embryonal cancers of the lung parenchyma and pleural surfaces that account for 0.25%-0.5% of primary pulmonary malignancies in children. Pleuropulmonary blastomas are classified as cystic (type I), mixed cystic and solid (type II), and solid (type III). Pleuropulmonary blastoma occurs in the same age group (0-6 years) as other more common solid tumors such as neuroblastoma and Wilms tumor. Differential diagnosis includes metastasis from Wilms tumor and macrocystic congenital pulmonary airway malformation (CPAM). A key pathologic and genetic discriminator is the DICER1 germline mutation found in patients with pleuropulmonary blastoma. Imaging, histopathologic, and clinical data are important to use in conjunction in order to determine the diagnosis and risk stratification of pleuropulmonary blastomas. Survival varies from poor to good, depending on type. However, the spectrum of pleuropulmonary blastoma is insufficiently understood due to the variable presentation of this rare disease. We present a current review of the literature regarding pleuropulmonary blastomas in this article.

The conventional drug discovery pipeline has proven to be unsustainable for rare diseases. Herein, we discuss recent advances in biomedical knowledge mining applied to discovering therapeutics for rare diseases. We summarize current chemogenomics data of relevance to rare diseases and provide a perspective on the effectiveness of machine learning (ML) and biomedical knowledge graph mining in rare disease drug discovery. We illustrate the power of these methodologies using a chordoma case study. We expect that a broader application of knowledge graph mining and artificial intelligence (AI) approaches will expedite the discovery of viable drug candidates against both rare and common diseases.

Key Points Severe bone marrow failure was primarily observed in early childhood in children with biallelic SBDS mutations.Absolute neutrophil counts were positively associated with age (P < .0001) in patients with biallelic SBDS mutations., Visual Abstract, Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with age could guide clinical management, but data are limited for this rare disease. We conducted a cohort study of 153 subjects from 143 families with confirmed biallelic SBDS mutations enrolled on the North American Shwachman Diamond Registry or Bone Marrow Failure Registry. The SBDS c.258 + 2T>C variant was present in all but 1 patient. To evaluate the association between blood counts and age, 2146 blood counts were analyzed for 119 subjects. Absolute neutrophil counts were positively associated with age (P < .0001). Hemoglobin was also positively associated with age up to 18 years (P < .0001), but the association was negative thereafter (P = .0079). Platelet counts and marrow cellularity were negatively associated with age (P < .0001). Marrow cellularity did not correlate with blood counts. Severe marrow failure necessitating transplant developed in 8 subjects at a median age of 1.7 years (range, 0.4-39.5), with 7 of 8 requiring transplant prior to age 8 years. Twenty-six subjects (17%) developed a myeloid malignancy (16 myelodysplasia and 10 acute myeloid leukemia) at a median age of 12.3 years (range, 0.5-45.0) and 28.4 years (range, 14.4-47.3), respectively. A lymphoid malignancy developed in 1 patient at the age of 16.9 years. Hematologic complications were the major cause of mortality (17/20 deaths; 85%). These data inform surveillance of hematologic complications in SDS.

Almost 1 in 10 individuals can suffer from one of many rare diseases (RDs). The average time to diagnosis for an RD patient is as high as 7 years. Artificial intelligence (AI)-based positron emission tomography (PET), if implemented appropriately, has tremendous potential to advance the diagnosis of RDs. Patient advocacy groups must be active stakeholders in the AI ecosystem if we are to avoid potential issues related to the implementation of AI into health care. AI medical devices must not only be RD-aware at each stage of their conceptualization and life cycle but also should be trained on diverse and augmented datasets representative of the end-user population including RDs. Inability to do so leads to potential harm and unsustainable deployment of AI-based medical devices (AIMDs) into clinical practice.

Leukemia is a rare disease associated with a high mortality rate. The presence of unilateral or bilateral serous retinal detachment (SRD) as a sign of choroidal infiltration can be one of the manifestations of acute leukemia, both as a primary sign or in a relapse. We consolidated the literature on SRD as a sign of leukemic choroidopathy regarding its epidemiology, clinical manifestations, and main imaging diagnostic tools. Well-documented cases regarding acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), relapsed ALL and relapsed AML published until September, 2020, in peer reviewed journals were included. The literature shows an interesting range of choroidal infiltration cases assessed by modern imaging techniques, such as optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and fluorescein angiography (FA). These tools allow choroidal assessment and better understanding and characterization of this rare condition. Complete ophthalmological workup should be performed in these patients using both FA and EDI-OCT to assess the choroidal anatomy and integrity. An increase in choroidal thickness measured with EDI-OCT can reveal active disease and potentially diagnose a leukemic relapse promptly.

Susac syndrome is a rare disease affecting mainly young women, characterized by a microangiopathy limited to the cerebral, retinal, and cochlear vessels. Although the pathophysiology of Susac syndrome is not yet fully elucidated, recent advances favour a primitive vasculitis affecting the cerebral, retinal and cochlear small vessels. Susac syndrome must be recognized in the presence of the pathognomonic clinical triad associating: 1/subacute encephalopathy with unusual headache and pseudopsychiatric features associated with diffuse white matter, grey matter nuclei and specifically corpus callosum lesions on brain MRI; 2/eye involvement that may be pauci-symptomatic, with occlusions of the branches of the central artery of the retina at fundoscopy and arterial wall hyperfluorescence on fluorescein angiography; and 3/cochleo-vestibular damage with hearing loss predominating at low frequencies on the audiogram. Relapses are frequent during an active period lasting approximately 2 years. Eventually, the disease resolves but isolated retinal arterial wall hyperfluorescence without new occlusions may recur, which should not lead to treatment intensification. First-line treatment consists of a combination of anti-aggregants and high dose corticosteroids. In refractory patients or in case of relapse, immunomodulatory molecules such as intravenous immunoglobulins or immunosuppressive drugs such as mycophenolate mofetil, cyclophosphamide or rituximab should be started. Unfortunately, sequelae-mostly hearing loss- remain frequent in these young patients.

Spontaneous coronary artery dissection is an infrequent cause of acute coronary syndrome with comparable clinical features. Previously considered a rare disease, recent scientific interest has revealed spontaneous coronary artery dissection as an important differential diagnosis of acute coronary syndrome, especially in young women, during pregnancy or postpartum, and in patients with fibromuscular dysplasia or other arteriopathies. However, there remain many uncertainties regarding pathophysiology, risk factors, acute treatment, and optimal long-term management. The aim of this review is to summarize current scientific evidence on epidemiology, management, and outcomes.

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter’s syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

Background Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.

Infected aortic aneurysm is a rare disease and is often overlooked as a source of infection in septic elderly patients. We present a case of a septic elderly man with a ruptured infected aortic aneurysm caused by Salmonella enteritidis. This condition was treated non-surgically with percutaneous endovascular aneurysm repair and antibiotics. The postoperative recovery was complicated a month later by spondylodiscitis and psoas abscess. He underwent radiologically guided drainage of the psoas abscess and was placed on lifelong suppressive antibiotics. We discuss the aetiology, treatment options and complications of this condition.

A previously fit and well 53-year-old man was referred to the otolaryngology clinic with intermittent stridor and was found to have bilateral vocal fold paresis. Subsequent airway compromise necessitated emergency surgical tracheostomy. The man was discharged home with tracheostomy in situ and a diagnosis of idiopathic bilateral vocal cord palsy, as all primary investigations were negative. Neurological disease was suspected following readmission to hospital several weeks later with diplopia. Electromyography and serum antibody testing confirmed a diagnosis of anti-muscle-specific tyrosine kinase antibody positive myasthenia gravis (MuSK-MG); a subset of MG where autoantibodies are directed against MuSK. Resolution of bilateral vocal fold paresis was found 8 months after a short course of immunoglobulin (intravenous immunoglobulin (IVIg)) and daily mycophenolate therapy was commenced. Multidisciplinary teamwork between ear, nose and throat surgeons, neurologists and speech therapists enabled successful decannulation of tracheostomy. The patient has recovered well and remains minimally symptomatic.

Primary Bartholin gland carcinoma (BGC) is an extremely rare disease. It typically presents in elderly women. It can be confused with Bartholin gland cyst, which is a benign condition leading to a delay in diagnosis and treatment. We are presenting a case report of BGC in a 35-year-old woman, which has created a diagnostic as well as therapeutic dilemma.

Objective: This scoping review aims to comprehend the nature and the extent of the available evidence regarding methods to assess patients with epidermolysis bullosa (EB). Introduction: Inherited EB is a rare genodermatosis characterized by extreme fragility of the skin and mucous membranes, which gives rise to the formation of blisters and ulcers following minor trauma. Due to its heterogeneous presentation, EB is significantly misdiagnosed, requiring a broader assessment to ensure an early clinical suspicion and better quality of care for the disease-related morbidities. Inclusion criteria: We will include human-based research articles based on qualitative or quantitative methods published in peer-reviewed journals that describe methods to assess EB patients, particularly those related to diagnosis, screening, classification, stratification, and follow-up. Only articles with full text available, published between 2018 and 2023, and written in English and Spanish will be included. Methods: The search strategy will be developed by a librarian and conducted on six databases. Selection of studies will be independently conducted by calibrated reviewers through the title, abstract, and full-text screening, followed by data charting. Quantitative (e.g., frequencies and percentages) and qualitative (e.g., classification of assessment methods) synthesis will be conducted.

Usher syndrome is a rare genetic disorder characterized by hearing loss and progressive vision loss, often leading to total blindness, affecting approximately 400,000 patients worldwide and making it a leading cause of deaf-blindness. While traditional treatments have focused on symptom management and support, recent advancements in gene therapy have sparked hope for potential cures. Gene therapy has shown remarkable success in treating certain retinal disorders, leading to optimism within the scientific community. However, the development and implementation of gene therapy for Usher syndrome present significant challenges. This scoping review aims to address the lack of comprehensive research into the limited translation of pre-clinical findings to clinical applications in Usher syndrome gene therapy. By identifying key obstacles at different stages of research, including pre-clinical studies, clinical trials, and economic and regulatory aspects, the review seeks to provide insights for future studies and improve the chances of developing effective gene therapy for Usher syndrome. The ultimate goal is to enhance the quality of life for individuals affected by this condition and pave the way for transformative therapeutic interventions.