Survey of medical genetic services in Italy: year 2011

The Italian Society of Human Genetics (SIGU) launched in 2012 a survey designed to scrutinize the 2011 activities of the Italian Medical Genetic Services, to compare the results with previous data collections, and to update the national scenario. SIGU had previously carried out six surveys to gather information on cytogenetic and molecular testing and clinical genetics activities, with the aim of providing guidance to the national and regional health systems to improve the organization of genetic services [1, 2].

Here, we report the results of this last study, providing an overview of the changes occurred over a 4-year period, highlighting the need for reviewing and improving the Italian genetic structure network, in line with the current public health requirements.

The survey refers to the medical genetic activities performed in Italy from January 1st to December 31st, 2011. This study was carried out by the Bambino Gesù Children Hospital in Rome, in collaboration with Orphanet-Italy, on behalf of SIGU. Ethical approval for this study was granted by SIGU. Data were gathered by an ad hoc questionnaire (http://​docs.​biomedia.​net/​SIGU/​Schema-Censimento_​SIGU-2011.​pdf) sent to genetic centers hosted by universities, research hospitals (Istituti di Ricovero e Cura a Carattere Scientifico - IRCCS), general hospitals, local health centers (Aziende Sanitarie Locali - ASLs) and commercial laboratories. The enrolled genetic centers were those registered and updated from the 2007 survey, integrated with others recruited through Orphanet database (www.​orpha.​net) or joining voluntarily to this initiative after learning of it during national scientific conferences or through the SIGU website (www.​sigu.​net). A verbal informed consent was obtained from participants.

Questions from previous surveys were reiterated and new ones added, in order to achieve information on the activities of immunogenetic laboratories and diagnostic tests becoming available in more recent years (i.e. microarrays). Entered data were based on self-certification. Information was collected online from March to July 2012, using forms available in a dedicated website. Each participating center accessed the website through a private username and password assigned during the registration process. Requested data included total number and type of performed cytogenetic and molecular genetic tests, clinical genetic activities such as the number and type of genetic counseling sessions. Data concerning the personnel attending laboratories and clinical activities were also collected. The quality management system of the responding centers in terms of national accreditation standards and international certifications was investigated, together with national and international External Quality Assessment enrolment. By comparing the number of analyses with the number of diagnoses confirmed by the test results, appropriateness was evaluated for the following entities: achondroplasia, Angelman, DiGeorge, fragile X-mental retardation, Noonan, Prader-Willi and Williams syndromes, ankylosing spondylitis and coeliac diseases. Appropriateness was investigated also for CGH (Comparative Genomic Hybridization) and SNPs (Single Nucleotide Polymorphisms) array tests.

The survey of the Italian medical genetic centers in year 2011 was carried out on the behalf of SIGU. This study aimed at providing indications to the national and regional public health systems, in agreement with the Regional Health System request to rationalize and integrate the public genetic laboratories under the pressure of the spending review and the need to improve efficiency. Indeed, the national health system is fully supporting the cost of genetic testing requested by the specialists, with some limitations for prenatal testing in women under the age of 35 years and/or without any specific indication. Accordingly to previous reviews, the number of genetic services was exceeding that required against the approximately 60,000,000 total inhabitants. Indeed the Minister of Health and the Italian Regions suggested that the maximums should be 1,000,000 inhabitants for every clinical genetics facility between 500,000 and 1,000,000 inhabitants for every cytogenetic laboratory and not less than 3,000,000 inhabitants for every molecular genetic laboratory (http://​www.​salute.​gov.​it/​imgs/​c_​17_​pubblicazioni_​908_​allegato.​pdf). The total number of genetic services in Table 1 clearly attests an oversize in all kinds of services.

As shown in this report, the coverage of the Italian territory by genetic testing facilities is one of the highest in Europe. In addition there is not equal distribution of the genetic services across the country, mainly attributable to economic reasons, since both public and private genetic services initially began in the rich regions of Northern Italy, which also are the most densely inhabited [2]. To date, only a few Italian regions have implemented strategic plans for reducing the number of centers through a coordination of their activities [4].

The SIGU 2011 survey evidenced a slightly lower number of genetic services compared to the 2007 data and confirmed that more than 50 % of all genetic services were located in Northern regions. A total of 3246 health professionals worked in these services, 44 % of which were biologists or biotechnologists as compared to only 21 % of technicians, an Italian anomaly contrasting the trend observed in other European countries and mainly attributable to the availability of the former to accept scholarships.

In the last decade guidelines regulating the activities of clinical and laboratory genetic services were jointly developed by the Ministry of Health and the Italian Regions, establishing roles and functions of genetic services [1]. According to National and Regional Health System, public Medical Genetics Services must operate within a Quality Management System, accredited by institutional bodies. Quality is defined by a number of requirements, which are not limited to organizational, professional, technical, procedural and communication elements. A significant improvement in the adoption of Quality Management Systems was registered in 2011, with respect to 2007. Indeed, 74 % of genetics structures turned out to be institutionally accredited, 57 % to be also voluntarily certified according to ISO 9001 standard (28 % in 2007) and a few voluntarily accredited according to ISO 15189. About 5 % of genetic services voluntarily accredited according to the quality standard for genetic structures elaborated by SIGU (www.​sigu.​net). The Italian state of quality systems within genetic testing services is similar to the European overview provided by Berwouts et al. [5]. Again, a North to South gradient was registered, with the majority of the accredited/certified services being located in Northern regions.

Collected data, showed that only 20 % of cytogenetic laboratories participated in the accredited CEQAS (formerly CEQA) and 44 % in the Istituto Superiore di Sanità (ISS, EQA national provider) schemes. Only a minority of the molecular laboratories stated they participated in an EQA scheme for cystic fibrosis. The participation in EQA is an established tool for improving quality, educating laboratory staff and directing laboratories towards best practices. National rules establish that medical laboratories shall participate in EQA scheme in order to be institutionally accredited, but appropriate checks to verify the participation of the genetic laboratories in EQA are only occasionally carried out by responsible bodies.

As shown in this report, the coverage of the Italian territory by genetic testing facilities is one of the highest in Europe. Table 4 shows that the 50 % of genetic tests available in Europe at time of survey were available also in Italy (902 genes investigated in 2011 compared to the 556 disease genes in 2007). Data collected by Orphanet-Italy referring to year 2012 figure showed an additional increase, with 1107 investigated disease genes. This positive trend places Italy at the fourth position in Europe, after Germany, Spain, and France [3]. In the case of tests not available in Italy, disease-gene analysis is performed using cross-border facilities. According to the Kääriäinen European survey [6] including also data from Italy, about the 3 % of genetic analyses in Europe are performed cross-border.

The need for a revision of the national molecular diagnostic network and for a diversification of the offer are supported by the results of the present survey, showing that testing of 15 disease-genes only accounted for 70 % of all molecular analyses in 2011. In addition, the demand of molecular tests has increased by a figure of 20 % from 2007 onwards, and cytogenetic analyses has reached a plateau of around 300,000 tests per year. Compared with the results registered by the 2007 census, the request of molecularly testing the susceptibility to common disorders and complex phenotypes was not increased, the analysis of thrombophilia cascade genes and HLA accounting for about 30 % of all molecular tests.

The request of constitutional prenatal and postnatal chromosome analyses has decreased in recent years. In particular, the number of genetic tests in amniocytes, which had been stable between 2004–2007, decreased in the years preceding the present survey, while the number of test on chorionic villi, increased by about 2500 per year in 2007–2011, stabilizing at around 25,500. It is expected that the decreasing trend of invasive prenatal tests will be further corroborated in the coming years, due to introduction of Non-Invasive Prenatal Testing (NIPT) into the diagnostic set.

The reduction of constitutional postnatal cytogenetic tests appears mainly related to the decrease of FISH analyses, which was expanded in the early 2000s, in parallel with the increased availability of commercial probes testing for cryptic deletions and supernumerary markers. A similar trend was also seen prenatally, with a consistent decrease of FISH tests. Between 2007–2011, FISH analyses had been progressively substituted by microarrays testing, as shown by the 8290 postnatal and 1862 prenatal tests (18 % of the total) in 2011, compared to 1443 and 393 respectively in 2007. The reduction in FISH prenatal tests was related also to the widespread use of QF-PCR for detecting major aneuploidies.

By contrast, oncological cytogenetic tests had increased by 58 %, mainly as a consequence of the wider introduction of FISH interphase analysis in genetic centers as documented by Table 3. One possible reason is the adoption of interphase FISH for detecting cryptic chromosome rearrangements in neoplastic disorders as recommended by the international guidelines.

As to previous concerns on the appropriateness of genetic testing requested by referring clinical geneticists, the 2011 results show an increase in the confirmed diagnoses for DiGeorge/Velocardiofacial and Williams syndromes, and a significant decrease for Prader-Willi syndrome compared to 2007 (see Table 7).

Only 12 % of all genetic analyses were accompanied by genetic counseling, in contrast with international [7] and national recommendations [8, 9]. Inappropriate replacement of the patient communication session by professionals of contiguous fields could account for the poor detection rate in these syndromes.

Since 2011 no substantial changes have been introduced in the Italian public genetic diagnostic field. In fact, the more recently developed tests (NGS: Next Generation Sequencing; NIPT) have not yet entered in the diagnostics setting and remain restricted to a research application. Public healthcare in Italy is now administrated on a regional basis and a concerted effort must be made to review and rationalize the network of genetic services nationally, taking into account the results of this present survey. In fact, this study provides a real and detailed representation about the logistic of the genetic centers, the number of performed genetic tests, the quality of provided services, the appropriateness of genetic test requests and the number of employees. Within this setting, a number of recommendations can be given for improving genetic services in Italy, which is at present oversized and nonharmonious. Some priority issues are emerging, including management of quality systems in terms of accreditation, certification, and EQA participations; accessibility of pre-test and post-test genetic counseling; the need of increasing availability of genetic testing for rare diseases; the development of national plans and strategies for implementing next generation technologies and advising on the clinical utility of genetic testing for complex disorders. The quality standard for genetic structures elaborated by SIGU may be adopted by a national competent body responsible for the specific accreditation and quality assurance of the genetic services. Another challenge, focused by Battista et al. [4], refers to the need of reconfiguring the professional roles and responsibilities. An additional effort concerns the education and training of those prescribing genetic tests, which should be utilized as a valuable support to good clinical practice and evidence based medicine. A parallel commitment must be to inform citizens, nowadays exposed to an ever more present and available direct-to-consumergenetic testing which has little proven clinical utility.

This study provides a real and detailed representation about the logistics of the genetic centers operating in Italy, the quality of their provided services, the number of performed genetic tests, and the number of employees. There are too many genetic services given the population size of Italy and they are not equally distributed across the country. Quality assurance of the genetic services may be improved through a specific accreditation standard. Good clinical practice and evidence based medicine may be implemented through the education and training of the people involved in the prescriptions of genetic tests. The finding that 70 % of all molecular analyses performed in 2011 was related to only 15 disease-genes, strongly supports the need for a revision of the national molecular diagnostic network. All together, these results provide information useful for improving genetic services in Italy.