Patient registries serve to overcome the research limitations inherent in the study of rare diseases, where patient numbers are typically small. Despite the value of real-world data collected through registries, adequate design and maintenance are integral to data quality. We aimed to describe an overview of the challenges in design, quality management, and maintenance of rare disease registries.A systematic search of English articles was conducted in PubMed, Ovid Medline/Embase, and Cochrane Library. Search terms included “rare diseases, patient registries, common data elements, quality, hospital information systems, and datasets”. Inclusion criteria were any manuscript type focused upon rare disease patient registries describing design, quality monitoring or maintenance. Biobanks and drug surveillances were excluded.A total of 37 articles, published between 2001 and 2021, met the inclusion criteria. Patient registries covered a wide range of disease areas and covered multiple geographical locations, with a predisposition for Europe. Most articles were methodological reports and described the design and setup of a registry. Most registries recruited clinical patients (92%) with informed consent (81%) and protected the collected data (76%). Whilst the majority (57%) collected patient-reported outcome measures, only few (38%) consulted PAGs during the registry design process. Few reports described details regarding quality management (51%) and maintenance (46%).Rare disease patient registries are valuable for research and evaluation of clinical care, and an increasing number have emerged. However, registries need to be continuously evaluated for data quality and long-term sustainability to remain relevant for future use.

Ciliopathies give rise to a multitude of organ-specific pathologies; obtaining relevant primary patient material is useful for both diagnostics and research. However, acquisition of primary ciliated cells from patients, particularly pediatric patients, presents multiple difficulties. Biopsies and blood samples are invasive, and patients (and their parents) may be reluctant to travel to medical centers, especially for research purposes. We sought to develop non-invasive methods of obtaining viable and ciliated primary cells from ciliopathy patients which could be obtained in the home environment. We introduce two methods for the non-invasive acquisition of primary ciliated cells. In one approach, we collected spontaneously shed deciduous (milk) teeth from children. Fibroblast-like cells were observed after approximately 2 weeks of culture of fragmented teeth. Secondly, urine samples were collected from children or adults. Cellular content was isolated and after approximately 1 week, renal epithelial cells were observed. Both urine and tooth-derived cells ciliate and express ciliary proteins visible with immunofluorescence. Urine-derived renal epithelial cells (URECs) are amenable to 3D culturing, siRNA knockdown, and ex vivo drug testing. As evidence continues to accumulate showing that the primary cilium has a central role in development and disease, the need for readily available and ciliated patient cells will increase. Here, we introduce two methods for the non-invasive acquisition of cells with primary cilia. We believe that these cells can be used for further ex vivo study of ciliopathies and in the future, for personalized medicine.

In the past, an anteriorly located anus was often misdiagnosed and treated as an anorectal malformation (ARM) with a perineal fistula (PF). The paper aims to define the criteria for a normal anus, an anterior anus (AA) as an anatomic variant, and milder types of ARM such as congenital anal stenosis (CAS) and PF. An extensive literature search was performed by a working group of the ARM-Net Consortium concerning the subject “Normal Anus, AA, and mild ARM”. A consensus on definitions, clinical characteristics, diagnostic management, and treatment modalities was established, and a diagnostic algorithm was proposed. The algorithm enables pediatricians, midwives, gynecologists, and surgeons to make a timely correct diagnosis of any abnormally looking anus and initiate further management if needed. Thus, the routine physical inspection of a newborn should include the inspection of the anus and define its position, relation to the external sphincter, and caliber. A correct diagnosis and use of the presented terminology will avoid misclassifications and allow the initiation of correct management. This will provide a reliable comparison of different therapeutic management and outcomes of these patient cohorts in the future.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10⁻⁷). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.