Prenatal diagnoses of congenital malformations have increased significantly due to high-resolution prenatal imaging. However, discussing these diagnoses with expectant parents remains challenging due to the varied outcomes associated with congenital malformations. Comprehensive prenatal genetic testing, including chromosomal microarray, exome sequencing, and genome sequencing, has become essential for improving prognostic accuracy.
The diagnostic yield of these tests depends on the specific malformations present. Prenatal genetic diagnosis enhances diagnostic clarity, informs pregnancy decisions, aids in neonatal care planning, and assists in reproductive planning. Although the turnaround time for comprehensive genetic testing results has improved, it still poses a challenge, especially for parents making decisions. The uncertainty of many genetic testing results necessitates appropriate genetic counseling to help parents understand the diagnosis and prognosis.
This review details available prenatal genetic testing options, discusses their impact on care using case examples, and consolidates current literature on the yield of genetic testing for diagnosing congenital malformations. Read the full article here.
Rare diseases are an often chronic and progressive group of conditions affecting more than 30 million people in Europe. These diseases are associated with significant direct and indirect costs to a spectrum of stakeholders, ranging from individuals and their families to society overall. Further quantitative research on the economic cost for children and their families living with a rare disease is required as there is little known on this topic.
Patient registries are crucial for rare disease management. However, manual registry construction is labor-intensive and not user-friendly. The aim of this study is to establish Hong Kong’s first computer-assisted patient identification tool for rare diseases, starting with Inborn errors of metabolism (IEM).
Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study is to determine the metabolomic profile that characterizes PWS compared to EOB.
The Dyke-Davidoff-Masson syndrome (DDMS) is an uncommon neurological disorder whose prevalence is not yet known. There have only been 21 adult manifestations of this rare brain disorder, out of around 100 cases previously documented. Diagnosis is challenging because of the complexity of radiological findings and clinical symptoms, which include ventricle dilation, hypertrophy of the cranial bones, increased pneumatization of the sinuses, and cerebral hemisphere atrophy. It can be inherited or acquired from infections, brain hemorrhage, and hypoxia during pregnancy. Usually, neuroimaging is used to diagnose it. This case study reports the case of a 17-year-old girl who had complex partial seizures at the age of 17 and right-side paralysis since she was three years old. Read the full article 
Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration. The aim of this article is to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease.
Rare diseases have become an increasingly important public health priority due to their collective prevalence. While the approval of orphan drugs requires supportive data from stringent pre-market studies, these data lack the ability to describe the causes of treatment response heterogeneity. Investigation of the pharmacogenomics can potentially lead to the development of new therapeutics, help inform rational use criteria in drug policy, and improve the understanding of underlying disease pathophysiology. In the context of rare diseases where cohort sizes are smaller than ideal, ‘small data’ and ‘big data’ approaches to data collection and analysis should be combined to produce the most robust results. This article presents the importance of studying drug response in parallel to other research initiatives in rare diseases, as well as the need for international collaboration in the area of rare disease pharmacogenomics. Read the full article 
The objective of this study is to estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy and other mutations, in the population with Prader-Willi syndrome (PWS).
Institute for Rare Diseases advances with it’s 11-th EU project – BUR-EB: Changes in the Socio-economic Burden of Epidermolysis Bullosa in Europe. 
Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. In this study the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates are tested. Identification of transthyretin cardiac amyloidosis and Fabry disease is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes.