Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, growth deficiency, intellectual disabilities, unusual dermatoglyphic patterns, and skeletal abnormalities. The incidence of hip dislocation in Kabuki syndrome ranges from 18% to 62%. We reviewed the outcomes of management of hip dislocations in patients with Kabuki syndrome with special attention to the diagnostic processes for hip dislocation and Kabuki syndrome. Among 30 patients with mutation-confirmed Kabuki syndrome, we selected six patients who had hip dislocations and reviewed their medical records and plain radiographs. The modes of presentation and diagnostic processes for both hip dislocations and Kabuki syndrome were investigated. The management and treatment outcomes of hip dislocations in patients with Kabuki syndrome were evaluated. The management of hip dislocation by conservative or surgical method showed successful results. Awareness of Kabuki syndrome could lead to an early diagnosis of this rare disease in patients with hip dislocation and allow for early detection of other underlying conditions and multidisciplinary management. For more information click here.
In a meeting held in Brussels last 6th February, the Commission introduced a new project to provide technical assistance to the ERNs for the development, appraisal and implementation of Clinical Practice Guidelines (CPGs) and Clinical Decision Support Tools (CDSTs). This 4 years contract will enable the ERNs to adopt a common methodology and develop their own decision-making tools: 48 new CPGs are expected and 120 existing CPGs will be adapted to the specific rare diseases they are addressing. For more information click here.
Adrenocorticotropic hormone-dependent Cushing syndrome, known as Cushing disease (CD), is a rare disease in paediatric patients, the signs and symptoms of which differ from those seen in adult patients. We included four consequent patients in the study, 7-15 years old, with CD confirmed by laboratory tests and finally by histology ex-aminations after surgery. The data were retrospectively retrieved from the medical records of all the patients from the years 2012-2018. In each case of the coexistence of growth velocity inhibition (not necessarily short stature) with the weight gain (not necessarily obesity) and the appearance of hyperandrogenism and depressive-anxiety disorders, biochemical diagnostics of CS should be performed. Obesi-ty could be a chronic complication of CD in childhood, even after effective neurosurgery treatment. For more information click here.
Whipple’s disease is a very rare disease needing a long-term treatment. The most frequent symptoms are recurrent arthralgia or arthritis, chronic diarrhea, abdominal pain, and weight loss. In this article, we have highlighted the main clinical features and diagnostic procedures that lead to the diagnosis and comment on the clinical response, treatment, and the factors of relapse. In current practice, it is highly difficult to diagnose Whipple’s disease. In order to decrease the delay between the first symptoms and the diagnosis, effective tools such as saliva and stools PCR should be used because higher delays of diagnosis lead to a higher number of relapses. For more information click here.
Superior mesenteric artery syndrome (SMAS), also known as Wilkie’s syndrome, is an exceedingly rare condition concerning intestinal obstruction. SMAS occurs when the space between the superior mesenteric artery (SMA) and the abdominal aorta narrows, resulting in compression of the duodenum. Functionally, the SMA supplies the distal duodenum, two-thirds of the transverse colon, and the pancreas. The location of the SMA is at about the level of the first lumbar vertebra branching off the anterior portion of the abdominal aorta. Generally, SMAS is due to rapid, excessive weight loss, resulting in the loss of the duodenal fat pad. The loss of the fat pad consequently changes the angle between the abdominal aorta and the SMA, or aortomesenteric angle, causing intestinal obstruction. Typical symptoms of acute cases of SMAS include postprandial abdominal pain, nausea, and vomiting; however, chronic cases may present with vague gastrointestinal symptoms and further weight loss. Herein, we discuss the case of a woman with chronic abdominal pain and previous substantial weight loss in whom we note features consistent with SMAS. For more information click here.
Whole genome and exome sequencing is a standard tool for the diagnosis of patients suffering from rare and other genetic disorders. The interpretation of the tens of thousands of variants returned from such tests remains a major challenge. Here we focus on the problem of prioritising variants with respect to the observed disease phenotype. We hypothesise that linking patterns of gene expression across multiple tissues to the phenotypes will aid in discovering disease causing variants. To test this, we construct classifiers that learn associations between tissue-specific gene expression and disease phenotypes. We find that using Genotype-Tissue Expression project (GTEx) expression data in conjunction with disease agnostic variant prioritisation methods (CADD or MetaSVM) results in consistent improvements in classification accuracy. Our method represents a previously overlooked avenue of utilising existing expression data for clinical diagnostics, and also opens the door to use of other functional genomic data sets in the same manner. For more information click here.
The objective is to identify relevant efficacy parameters essential in designing clinical trials for brain-penetrant therapies for Gaucher disease, we evaluated cognitive function longitudinally in 34 patients with Gaucher disease type 3 seen at the NIH Clinical Center. Individuals were tested with age-appropriate Wechsler Intelligence Scales administered between 1 and 18 times over 29 years. Variation in all IQ domains was not linear with time and was best characterized with the coefficient of variation (SD/mean) for each individual. Mixed-effects regressions were used to determine whether IQ was associated with clinical features. Models were controlled for variation in test version, participant identification, and test administrator. The observed variation in IQ in Gaucher disease type 3 across the cohort and within single individuals over time may be characteristic of other neuronopathic diseases. Therefore, to reliably use IQ as an efficacy measure in any clinical trial of neurotherapeutics, a normal variation range must be established to assess the clinical relevance of any IQ change. For more information click here.
Member States meet with the European Commission in Brussels on January 29th to discuss the protection of personal data in the health sector
There will be a meeting between the Member States and the European Commission in Brussels on January 29th, 2020 during which will be discussed the protection of personal data in the health sector. Also there will be a workshop, exploring how Member States are implementing the GDPR for the protection of personal data in the field of health, in order to identify possible differences and examine how this may affect the cross-border exchange of health data in the EU. It is the first of a three part series of workshops between January and April 2020, which will contribute to a legal study commissioned by the Commission in view of the future establishment of a European Health Data Space. For more information click here.
In recent years, many genes have been associated with chromatinopathies classified as “Cornelia de Lange Syndrome-like.” It is known that the phenotype of these patients becomes less recognizable, overlapping to features characteristic of other syndromes caused by genetic variants affecting different regulators of chromatin structure and function. Therefore, Cornelia de Lange syndrome diagnosis might be arduous due to the seldom discordance between unexpected molecular diagnosis and clinical evaluation. Here, we review the molecular features of Cornelia de Lange syndrome, supporting the hypothesis that “CdLS-like syndromes” are part of a larger “rare disease family” sharing multiple clinical features and common disrupted molecular pathways. For more information click here.
Hereditary angioedema (HAE) with C1 esterase inhibitor deficiency (C1-INH-HAE) is a rare disease that manifests with cutaneous and/or submucosal swellings due to uncontrolled activation of the contact/kinin system. Attacks recur with unpredictable frequency and severity, laryngeal edema is potentially lethal, and the disease burden may severely disrupt patients’ lives.Areas covered: This review provides an overview of lanadelumab, a human monoclonal antibody targeted against plasma kallikrein that was recently approved for prevention of symptoms in C1-INH-HAE.Expert opinion: The phase III HELP Study demonstrated the efficacy of lanadelumab in reducing HAE attacks. These positive results are being further confirmed in the open-label extension study. This agent addresses some of the limitations of existing prophylactic options as tolerability issues, the need for intravenous administration and frequent dosing. Therefore, lanadelumab can profoundly improve the quality of life of patients with C1-INH-HAE. For more information click here.