Androgen insensitivity syndrome (AIS) is a rare genetic disorder that affects the development of the male reproductive system in individuals with a 46,XY karyotype. In addition to physical impacts, patients with AIS may face psychological distress and social challenges related to gender identity and acceptance. The major molecular etiology of AIS results from hormone resistance caused by mutations in the X-linked androgen receptor (AR) gene. Depending on the severity of androgen resistance, the wide spectrum of AIS can be divided into complete AIS (CAIS), partial AIS (PAIS), or mild AIS (MAIS). Open issues in the treatment and management of AIS include decisions about reconstructive surgery, genetic counseling, gender assignment, timing of gonadectomy, fertility and physiological outcomes. Although new genomic approaches have improved understanding of the molecular causes of AIS, identification of individuals with AIS can be challenging, and molecular genetic diagnosis is often not achievable. The relationship between AIS genotype and phenotype is not well established. Therefore, the optimal management remains uncertain. The objective of this review is to outline the recent progress and promote understanding of AIS related to the clinical manifestation, molecular genetics and expert multidisciplinary approach, with an emphasis on genetic etiology.

Urogenital sinus (UGS) malformation, also known as persistent urogenital sinus (PUGS), is a rare congenital malformation of the urogenital system. It arises when the urethra and vaginal opening fail to form properly in the vulva and fuse incorrectly. PUGS can occur as an isolated abnormality or as part of a complex syndrome, and is frequently associated with congenital adrenal hyperplasia (CAH). The management of PUGS is not well-established, and there are no standardized guidelines on when to perform surgery or how to follow up with patients over the long term. In this review, we discuss the embryonic development, clinical evaluation, diagnosis, and management of PUGS. We also review case reports and research findings to explore best practices for surgery and follow-up care, in hopes of increasing awareness of PUGS and improving patient outcomes.

The aim of this study was to compare the effects of the pandemic on health-related quality of life (HRQoL), anxious-depressive symptoms, feelings of loneliness, and fear of COVID-19 between people with myasthenia gravis (MG) and healthy controls. We also wanted to know in which group the variable fear of COVID-19 interfered the most with the results. This cross-sectional study involved 60 people with MG and 60 healthy controls. Participants using an online platform completed a sociodemographic questionnaire, the Short Form-36 Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the revised UCLA Loneliness Scale and the Fear of COVID19 Scale (FCV-19S). The MG group reported worse levels in HRQoL indicators (p = 0.043- <.001), more severe anxiety-depressive symptoms (p = 0.002), and greater fear of COVID-19 (p < 0.001), but there were no differences in feelings of loneliness (p = 0.002). Furthermore, after controlling for the effect of the fear of COVID-19 variable, the differences remained for physical health indicators, but not for the most of psychosocial indicators (Social Functioning p = 0.102, η²_p = 0.023; Role Emotional p = 0.250, η²_p = 0.011; and HADS Total p = 0.161, η²_p = 0.017). The harmful effect of the COVID-19 pandemic was greater in the MG group, and the perceived fear of COVID-19 had also a greater impact among this group, which has increased its negative effect on their psychosocial health.

Trust in physicians is an important metric in shared decision-making. Many patients with rare diseases experience misdiagnosis or delayed diagnosis because of difficulties in diagnosis or access to specialists. What impact do these have on trust in physicians? This study focused on patients with rare diseases, evaluated the effects of a delayed diagnosis and misdiagnosis on trust in physicians, and clarified the backgrounds of patients who have experienced delayed diagnoses. Patients with any of the 334 intractable diseases in Japan were registered, and a questionnaire survey was conducted on 1,000 valid registrations. Scores were calculated on a five-point Likert scale, and Cronbach's alpha coefficient was calculated to determine internal consistency, which was 0.973. Independent sample t-tests and analysis of variance were used to compare average trust scores based on patient demographics. The mean trust in physician score of patients who waited ≤ 1 year until definitive diagnosis was 47.66 ± 11.69, while those of patients who waited > 1 year was 45.07 ± 11.63 (p = 0.004). The average trust scores of patients with or without a misdiagnosis were 46.69 ± 11.96 and 47.22 ± 11.65 (p = 0.550), respectively. Among patients with time to a definitive diagnosis of > 1 year, 62.8% had a period from symptom onset to initial hospital visit of > 1 year. A longer time to definitive diagnosis lowered the degree of trust in physicians. Many patients who experienced delayed diagnoses also had a long time from symptom onset to the initial medical visit. This aspect is important for understanding the background of patients who experienced delayed definitive diagnoses.

Intellectual disability (ID) and multiple congenital anomalies (MCA) are major contributors to infant mortality, childhood morbidity, and long-term disability, with multifactorial aetiology including genetics. We aim to set a diagnostic approach for genetic evaluation of patients with ID and MCA, which can be applied efficiently with a good diagnostic rate in Indonesia or other low resources settings. Out of 131 ID cases, twenty-three individuals with ID/global developmental delay (GDD) and MCA were selected from two-steps of dysmorphology screening and evaluation. Genetic analysis included chromosomal microarray (CMA) analysis, targeted panel gene sequencing, and exome sequencing (ES). CMA revealed conclusive results for seven individuals. Meanwhile, two out of four cases were diagnosed by targeted gene sequencing. Five out of seven individuals were diagnosed using ES testing. Based on the experience, a novel and comprehensive flowchart combining thorough physical and dysmorphology evaluation, followed by suitable genetic tests is proposed as a diagnostic approach to elucidate the genetic factor(s) of ID/GDD and MCA in low resources settings such as Indonesia.

Gout is the most common arthritis that affects more than 2% of adults in developed countries. 3% to 4% of gout is chronic refractory gout. Conventional treatments are considered invalid. A new drug, pegloticase is used to treat chronic refractory gout, and there are still many questions about efficacy and safety. We searched PubMed, web of science, and the Cochrane Library. Preprints and references of related literature were also considered. Related efficacy and safety indicators were statistically analyzed by Review Manager 5.4 to conduct meta-analysis. A total of one article and one clinical trial were included. Pegloticase is able to reduce serum uric acid and reduce tender joints, thereby improving joint function. But pegloticase has more adverse events. Pegloticase can be used to treat chronic refractory gout. However, Pegloticase has a higher risk of adverse events. Considering the efficacy and safety, the scope of clinical applications of pegloticase can be further widened in patients in good medical condition.

Leukoencephalopathy is a common finding on Magnetic Resonance Imaging (MRI), particularly in the elderly. A differential diagnosis may represent a very bet for clinicians when clear elements for diagnosis are lacking. Diffuse infiltrative "non mass like" leukoencephalopathy on MRI may represent the presentation of a very rare aggressive condition known as lymphomatosis cerebri (LC). The lack of orienting data, such as contrast enhancement on MRI or specific findings on examination of Cerebrospinal Fluid (CSF) or blood tests, may even far more complicate such a difficult diagnosis and orientate toward a less aggressive but time-losing mimic. A 69-old man initially presented to the Emergency Department (ED) complaining the recent appearance of unsteady walking, limitation of down and upgaze palsy, and hypophonia. Brain MRI revealed the presence of multiple, confluent hyperintense lesions on T2/Flair Attenuated Imaging Recovery (FLAIR) sequences involving either the withe matter of the semi-oval centres, juxtacortical structures, basal ganglia, or bilateral dentate nuclei. DWI sequences showed a wide restriction signal in the same brain regions but without any sign of contrast enhancement. Initial 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG PET) and CSF studies were not relevant. Brain MRI revealed a high choline-signal, abnormal Choline/N-Acetyl-Aspartate (NAA), and Choline/Creatine (Cr) ratios, as well as reduced NAA levels. Finally, a brain biopsy revealed the presence of diffuse large B-cell lymphomatosis cerebri. The diagnosis of lymphomatosis cerebri remains elusive. The valorisation of brain imaging may induce clinicians to suspect such a difficult diagnosis and go through the diagnostic algorithm.

Myasthenia gravis (MG) is a rare autoimmune disease that affects the neuromuscular junction. It is characterized by the production of heterogeneous autoantibodies that bind to the neuromuscular junction and alter neural transmission. Recently, more attention was given to MG-related antibodies and their clinical influence. In Lebanon, studies about MG are very rare. To date, there is still no research on the different autoantibodies developed by Lebanese MG patients. We conducted a study aimed at detecting the prevalence of different antibodies in a group of seventeen Lebanese patients with MG, and exploring their associations with clinical phenotypes and quality of life (QOL). MG antibody test in Lebanon is restricted only to two antibodies: acetylcholine receptor (anti-AChR) and muscle-specific kinase (anti-MUSK) antibodies. Results showed that 70.6% of patients were anti-AChR positive and all of them were anti-MUSK negative. Association between MG serological profiles, clinical outcomes and QOL was not significant. Together, current findings suggest that anti-MUSK antibody is not common and difference in antibody profile may not change the clinical phenotypes and QOL of MG Lebanese patients. In the future, it is recommended to check also for autoantibodies other than anti-AChR and anti-MUSK, which may reveal new antibody profiles and possible associations with clinical outcomes.

Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease characterized by dystrophic calcification of elastic fibres in the skin, retina and vascular wall. Data on cardiac involvement are inconsistent. Hence, we aimed to evaluate cardiorespiratory response to incremental cardiopulmonary exercise testing (CPET) in PXE. A total of 30 PXE patients (54.0 ± 11.2 years, 40.0% male) and 15 matched controls underwent symptom-limited incremental CPET. PXE patients presented an impaired peak work rate as compared to controls (84.2 ± 16.0% vs. 94.7 ± 10.4%, p = 0.03) that was accompanied by a lower peak oxygen uptake (in % predicted and mL/min/kg), reduced increments in oxygen uptake per increments of work rate (ΔV´O₂/ΔWR, 8.4 ± 3.0 mL/min/W vs. 11.3 ± 4.9 mL/min/W, p = 0.02), lower peak oxygen pulse (78.0 ± 12.3% vs. 90.6 ± 19.6%, p = 0.01) and reduced minute ventilation at peak exercise (V´E, 66.2 ± 16.8% vs. 82.9 ± 25.2%, p = 0.02). To summarize, we presently observed impairment in mainly cardiocirculatory parameters, whilst no substantial ventilatory limitation was detected. The potential implications of this finding for PXE management warrant further study.

Retroperitoneal fibrosis (RF) commonly leads to renal impairment due to compression of ureters, and around 8% of patients eventually progress to end-stage renal disease (ESRD). We present a case of RF in a 61-year-old female patient with neurofibromatosis type 1 (NF1) who developed ESRD. She presented with a postrenal acute kidney injury, being initially treated with an ureteral catheter. A magnetic resonance imaging of the abdomen showed parietal thickening of the right ureter, and she underwent right ureter reimplantation through bladder flap and psoas hitch. There was an extensive area of fibrosis and inflammation over the right ureter. Biopsy disclosed nonspecific fibrosis, which was consistent with RF. Although the procedure was successful, she developed ESRD. We review atypical presentations of RF and causes of renal injury in NF1. RF should be considered a possible cause of chronic kidney disease in patients with NF1, perhaps due to an unknown underlying mechanism.