EUROCAT – epidemiologijsko praćenje prirođenih mana u Europi

Registri prirođenih mana osnivaju se zato da bi se uspostavio nadzor nad pojavnošću prirođenih mana koje imaju sve veću važnost u strukturi morbiditeta i mortaliteta dojenčadi. U Europi već 25 godina djeluje EUROCAT - mreža regionalnih registara - koja godišnje nadzire oko1.2 milijuna porođaja. Ciljevi registra su prikupljanje osnovnih epidemologijskih informacija o prirođenim manama, rano otkrivanje izloženosti teratogenima, pojave nakupljanja u vremenu i prostoru, te evaluacija učinkovitosti organizacije i primjene primarne prevencije i prenatalnog probira na razini populacije. EUROCAT se pokazao kao djelotvorna mreža i infrastruktura za istraživanja na području etiologije i prevencije prirođenih mana. Hrvatski registar, sa središnjicom u Referentnom centru Ministarstva zdravstva za praćenje kongenitalnih anomalija Republike Hrvatske, djeluje od 1983. godine i obuhvaća četiri regije – Varaždin, Rijeku, Pulu i Koprivnicu. Š irenje registra na ostala područja Hrvatske značajno bi poboljšalo praćenje kvalitete i planiranje zdravstvene zaštite u trudnoći i ranom djetinjstvu

Osteogenesis imperfecta: klinička procjena i liječenje

Osteogenesis imperfecta (OI) is a phenotypically and molecularly heterogeneous group of heritable connective tissue disorders characterized by low bone mineral density, recurrent fractures, and bone deformities. Most cases of OI are inherited in an autosomal dominant manner and are caused by mutations in the COL1A1 and COL1A2 genes, leading to quantitative or qualitative defects in type 1 collagen. More recently, a number of other genes responsible for both recessive and dominant forms of this condition have been identifi ed. In this brief review, we discuss current understanding of clinical assessment, follow-up and pharmacological therapies for the treatment of OI. The multidisciplinary surveillance in patients with OI includes periodical hearing and vision testing, dental examination, spirometry or body plethysmography, evaluation of heart/valvular function, and neurological and psychological assessment. There is a need for regular assessment of bone mineral density (BMD) to evaluate treatment success and disease progression, and skeletal radiographs at the time of diagnosis and later as indicated by orthopaedists. Treatment of OI is aimed at preventing or controlling the symptoms present in individual patient with the main goals to decrease fracture rate, relieve bone pain, and provide suffi cient bone mass and good muscle strength promoting self-mobility and growth. This requires a multi-disciplinary approach, utilizing medical treatment, physical therapy, orthopedic surgery, and nutrition monitoring. Intravenous bisphosphonate therapy is the most widely used medical treatment. It has an evident eff ect on BMD of lumbar spine, femoral neck and total hip in growing children and can lead to vertebral reshaping after compression fractures, but no signifi cant eff ect on the risk of fractures has been observed in adults. Other novel promising therapies include teriparatide, combination therapy with antiresorptive and anabolic drugs, denosumab, transforming growth factor beta, sclerostin and cathepsin K inhibitors, and cell-based therapy, such as bone marrow or mesenchymal stem cell transplantation. Gene targeting approaches are still at early stages of investigation.Osteogenesis imperfecta (OI) je fenotipski i molekularno heterogena skupina nasljednih bolesti veziva obilježena smanjenom gustoćom kostiju, čestim lomovima i deformacijama. Većina OI-a nasljeđuje se autosomno dominantno i uzrokovana je mutacijama u genima COL1A1 i COL1A2, što dovodi do kvantitativnog ili kvalitativnog defekta kolagena tip 1. U posljednje vrijeme otkriven je veći broj gena koji su odgovorni za recesivne i dominantne oblike ove bolesti. U ovom kratkom pregledu razmatramo suvremeni pristup kliničkoj dijagnostici i praćenju te farmakološkom liječenju OI-a. Multidisciplinsko praćenje bolesnika uključuje povremeno testiranje sluha i vida, stomatološke preglede, spirometriju ili pletizmografi ju, evaluaciju funkcije srca/valvula, neurološke i psihološke kontrole. Potrebno je redovito pratiti vrijednosti gustoće kostiju (BMD) kako bi se utvrdio uspjeh liječenja i progresija bolesti, a nužne su i rengenske slike kostiju kod postavljanja dijagnoze i kasnije prema indikaciji ortopeda. Svrha liječenja je i da spriječi ili suzbije simptome prisutne kod pojedinog bolesnika, a glavni ciljevi su smanjiti broj lomova, suzbiti bol, poboljšati koštanu masu i mišićnu snagu te osigurati samostalnu pokretnost i rast. To zahtijeva multidisciplinski pristup u liječenju lijekovima, fi zikalnom terapijom, kiruškim ortopedskim zahvatima i odgovarajućom prehranom. Intravenska primjena bisfosfonata je najšire primjenjivan oblik medikamentoznog liječenja. Ona ima očit učinak na BMD slabinske kralježnice, vrata bedrene kosti i kukova djece u rastu, te može dovesti do preoblikovanja kralježaka nakon kompresijskih fraktura, ali nema značajnijeg učinka na rizik pojave lomova kod odraslih osoba. Druge nove obećavajuće terapije uključuju teriparatid, liječenje kombinacijom antiresorptivnih i anaboličih lijekova, denosumab, inhibiciju TGF-β (eng. transforming growth factor beta), sklerostina i kathepsina K te staničnu terapiju, poput transplantacije koštane srži ili mezenimalnih stanica. Genska terapija je još u ranim stadijima ispitivanja

Development of Genetics in the World and in Croatia – Forty Years of the Croatian Society of Human Genetics of the Croatian Medical Association

Resulting from several basic scientific disciplines, genetics has made impressive progress in the last century by discoveries of the heredity rules and genome structure, and by identification of the genes that determine the occurrence and characteristics of human diseases. In Croatia, the development of genetics began in the middle of the past century by the pioneering work of clinicians and basic scientists, which resulted in significant development of this scientific discipline that has quickly found its practical application in clinical genetics-cytogenetics, molecular genetics and prenatal diagnosis. The rapid advancement of technology and knowledge of genetics in recent decades has led to the development of genomics and related disciplines, entering the revolutionary new era of personalized medicine. Currently, much more data can be collected than interpreted. The data of electronic medical records, genomics, epigenetics, proteomics, metabolomics and microbiomics should be integrated and interpreted at the level of individual genome. Extensive use of new information will open a range of ethical issues that we must face timely. It is expected that in the forthcoming years, we will be able to learn more about genetics than what we have learned throughout the history of medicine. We must be prepared to welcome this new knowledge, reflecting on the positive and negative aspects of the latest achievements in the field of genetics. We hope that the experts dealing with human genetics in Croatia will successfully continue their work to enable practical application of the latest achievements in genetics, expanding our understanding of the concept of health and disease

Osteogenesis imperfecta - multi-systemic and life-long disease that affects whole family [Osteogenesis imperfecta - više-sustavna, doživotna bolest i njen utjecaj na obitelj]

Osteogenesis imperfecta or brittle bone disease, a heritable disorder of connective tissue, is the most common of the inherited disorders primarily affecting bone. There are approximately 400 individuals with OI in Croatia alone. It is estimated that twice that number is present, represented by individuals with mild OI in whom the diagnosis has not been made. Due to the relatively low number of patients in the general population, treating physicians have limited experience with this disease, either with children or adults. The basis of this disease in European populations is mostly the result of defects in the structure or processing of collagen type I, an important protein of the extracellular matrix of many tissues. Presently, molecular defects in 16 different genes have been discovered to result in at least one type of OI of which 14 are not COL1 mutation loci. Although fractures occurring with no injury or minor injury are the hallmark of OI, other non-mineralized tissues can be affected as well and the pathological changes can be present in skin, tendons, eyes, teeth and blood vessels. Clinical manifestations are very heterogeneous and numerous signs and symptoms such as blue sclera, deafness, abnormal teeth development, joint hypermobility, increased risk of hernias, capillary fragility, aneurysms etc. Although there is no cure for this disease, there are specific therapies that can reduce the pain and complications associated with OI. The purpose of this review is to provide a brief overview of the molecular basis of this disease, describe clinical presentations, as well as to present orthopaedic therapeutic modalities for the patients with OI

Novel duplication on chromosome 16 (q12.1-q21) associated with behavioral disorder, mild cognitive impairment, speech delay, and dysmorphic features: case report

We report on the 10-year follow-up and clinical, cytogenetic, and molecular investigation of a girl admitted for evaluation because of speech delay, learning difficulties, aggressive behavior, and dysmorphic facial features that included high forehead, round face, epicanthic folds, low-set dysplastic ears, flat nasal bridge, long flat philtrum, thin upper lip, small mouth, and short neck. The analysis of high-resolution GTG- and CTG-banding chromosomes suggested a de novo direct duplication of 16q12-q21 region and fluorescence in situ hybridization analysis with whole-chromosome specific 16 probe confirmed that the duplicated genetic material originated from the chromosome 16. Subsequently, array-based comparative genomic hybridization analysis with a ≈ 75 kb resolution showed a 9.92 Mb gain on the long arm of chromosome 16 at bands q12.1 through q21. To the best of our knowledge, this is the first case of duplication 16q12.1q21 described in literature. Several genes within the duplicated region are possibly correlated with clinical features present in our patient. Clinical and cytogenetic findings were compared with the small number of reported patients with pure duplications 16q, partially overlapping the one in our patient. Clinical phenotype seems to be distinctive between the proximal-intermediate and intermediate-distal regions of the long arm of the chromosome 16. In particular, we observed a set of dysmorphic features that could present a characteristic dup 16q11.2-q13 phenotype. The present study illustrates the advantages of an integrative approach using both conventional and molecular techniques for the precise characterization and genotype-phenotype correlation in patients with dysmorphism, behavioral problems, and learning difficulties