Communicating the risks of handling bats: analysing approaches used by Australian stakeholders in the context of Australian bat lyssavirus.

Australian bat lyssavirus (ABLV) is a member of the Lyssavirus genus of the Rhabdoviridae family and is found in Australian bat species. It is of public health concern because of the rabies-like syndrome it causes in humans, resulting in government health and wildlife agencies using varied communication approaches to inform targeted audiences about zoonotic risks associated with handling bats. Despite these warnings, the number of reports of human-bat interactions remains high. This paper details a survey conducted to analyse the approaches utilised by a range of stakeholders to educate and communicate warnings to their target audiences. The survey focused on identifying the target audiences, communication methods used, along with the message frequency, content, and perceived effectiveness. Analysis of the top three messages delivered by stakeholders revealed that over half were information-focused messages and over a third, instruction-focused. Stakeholders identified the need to balance messaging about bat handling risks with information regarding the vulnerable status of bats and their environmental significance. Whilst the most common and (perceived) effective method of communication was one-on-one discussions, it was also identified to be ineffective for targeting mass audiences leading stakeholders to recognise the need to adapt to more efficient means of communication. The outcomes of this study may be useful to improve risk communication strategies regarding ABLV in Australia.

Psoriatic alopecia.

Alopecia and other hair abnormalities occurring in patients with psoriasis were first recognized over four decades ago, yet psoriatic alopecia is not a well-known concept among clinicians. Alopecia may be directly related to the psoriasis itself, and can affect both the scalp and other parts of the body. On the scalp, psoriatic alopecia most commonly affects lesional skin, but may present as a generalized telogen effluvium. In most cases, there is regrowth of hair, but in rare cases it can cause scarring alopecia. Histological findings include features of psoriasis in the interfollicular epithelium, along with perifollicular inflammation and atrophy or loss of the sebaceous glands. Late changes include destruction of the hair follicle, with perifollicular fibrosis and 'naked' hair shafts lying free in the dermis. In addition to the hair loss caused by the psoriasis itself, data from population and genetic studies reveal that patients with psoriasis are at greater risk of developing alopecia areata. Psoriasis treatments may also contribute to hair loss. Application of topical preparations may cause hair loss through friction, and many of the systemic treatments used for psoriasis can also cause hair problems. Treatment with anti-tumour necrosis factor-α agents can precipitate de novo psoriasis and subsequent psoriatic alopecia.

Orthotopic models of pediatric brain tumors in zebrafish.

High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34 °C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34 °C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice.

Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway.

Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma pathogenesis. Yet, the role of this pathway in gliomagenesis remains controversial because of the lack of relevant animal models. Using the cytokeratin 5 promoter, we ectopically expressed a constitutively active zebrafish Smoothened (Smoa1) in neural progenitor cells and analyzed tumorigenic capacity of activated Shh signaling in both transient and stable transgenic fish. Transient transgenic fish overexpressing Smoa1 developed retinal and brain tumors, suggesting smoa1 is oncogenic in the zebrafish central nervous system (CNS). We further established stable transgenic lines that simultaneously developed optic pathway glioma (OPG) and various retinal tumors. In one of these lines, up to 80% of F1 and F2 fish developed tumors within 1 year of age. Microarray analysis of tumor samples showed upregulated expression of genes involved in the cell cycle, cancer signaling and Shh downstream targets ptc1, gli1 and gli2a. Tumors also exhibited specific gene signatures characteristic of radial glia and progenitor cells as transcriptions of radial glia genes cyp19a1b, s100ß, blbp, gfap and the stem/progenitor genes nestin and sox2 were significantly upregulated. Overexpression of GFAP, S100ß, BLBP and Sox2 was confirmed by immunofluorescence. We also detected overexpression of Mdm2 throughout the optic pathway in fish with OPG, therefore implicating the Mdm2-Tp53 pathway in glioma pathogenesis. In conclusion, we demonstrate that activated Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first OPG model not associated with neurofibromatosis 1.

Survey of Australian equine veterinarians evaluating their biosecurity training and perceptions and opinions about the management of the 2007 equine influenza outbreak.

OBJECTIVES: To evaluate the level of biosecurity training among Australian equine veterinarians and to assess their perceptions of biosecurity and infectious disease risk and their opinions about the management of the 2007 equine influenza (EI) outbreak. DESIGN: Cross-sectional study. METHODS: A survey was conducted among equine veterinarians attending the 2010 annual conference of the Equine Veterinarians Australia (EVA) in New South Wales, Australia. Data were collected using a self-completed questionnaire and analysed using Fisher's exact tests to assess veterinarians' levels of biosecurity training, their perceptions of infectious disease and views regarding the 2007 EI outbreak management. RESULTS: A total of 46 of the 196 (23.5%) attending veterinarians completed the questionnaire. Significantly greater proportions of recently graduated veterinarians received theoretical and practical biosecurity training at veterinary schools than their older counterparts. The majority of respondents considered their likelihood of spreading infectious diseases from one client's horse to another to be low (84%). More than half (58%) of the veterinarians considered that hand-washing/wearing gloves was very effective in preventing disease spread. However, around one-quarter (27%) reported a degree of reservation about the practicality of performing general biosecurity practices in everyday working life. Overall, veterinarians were satisfied with the EI outbreak response, but had mixed opinions about the control measures and communications used. CONCLUSION: Levels of biosecurity training and the frequency of biosecurity advice provided by veterinarians have increased over time, although the practicality of biosecurity practices is a concern for some veterinarians. Further investigations of the barriers to the use of various biosecurity practices are required in order to inform training programs.

The surgical management of neuroendocrine tumour hepatic metastases.

Although rare in incidence, patients with neuroendocrine tumours (NET) live for many years and so have a high prevalence, and NETs frequently metastasise to the liver (NLM). Numerous treatment options have been implemented both for cure, and to implement disease control. Surgical treatment consists of curative resection, palliative cytoreductive resection and transplantation. Complete surgical resection is possible only in a subset of people with NLMs due to various factors. Ablative therapies may also be used, either as an adjunct to surgery or as a primary treatment. The purpose of the article is to summarise surgical treatment strategies in the management of patients with hepatic neuroendocrine metastases.

Horse owners'/managers' perceptions about effectiveness of biosecurity measures based on their experiences during the 2007 equine influenza outbreak in Australia.

Following the first ever equine influenza outbreak in Australia in 2007, a study was conducted involving 200 horse owners and managers to determine their perceptions about effectiveness of biosecurity measures and the factors associated with these perceptions. Face-to-face interviews were conducted with horse owners/managers to obtain information about their perceptions of the effectiveness of biosecurity practices, their sources of information about infection control during the outbreak and their horse industry involvement. Two outcome variables were created from horse owners' responses to a 17-item question on the perceived effectiveness of various recommended equine influenza biosecurity measures: (a) a binary outcome variable (Low/High biosecurity effectiveness) and (b) a continuous outcome variable (the proportion of the 17 measures considered 'very effective'). These outcomes were used in binomial logistic and linear regression analyses, respectively, to determine factors associated with perceptions of biosecurity effectiveness. Variables with a p-value <0.05 in multivariable models were retained in the final models. The majority (83%) of the 200 horse owners and managers interviewed believed that more than half of the recommended equine influenza biosecurity measures were very effective for protecting their horses from equine influenza infection in the event of a future outbreak. Interviewees that were more likely to judge on-farm biosecurity measures as effective were those who received infection control information from a veterinarian during the outbreak, did not experience equine influenza infection in their horses, and those on small acreage premises (homes with horses on site). Greater levels of preparedness for a future equine influenza outbreak and greater interest in information about infection control were associated with a better perception about effectiveness of biosecurity measures. This study identified factors associated with horse owners' and managers' perception of effectiveness of biosecurity measures. These findings should be considered in the design of infection control programs.

From the horse's mouth: perceptions of the management of the 2007 equine influenza outbreak in Australia.

In August 2007, Australia experienced its first-ever outbreak of equine influenza, a highly infectious respiratory disease of horses. Although the outbreak spread over a large geographic area, it was eradicated within 5 months following a substantial disease control effort led by federal and state animal health authorities. Despite its timely control, this large-scale outbreak caused severe impacts on horse owners and industry participants. This study aimed to describe the perceptions of horse owners and managers, impacted by outbreak control measures, regarding the state government's animal health authority outbreak management. Participants were interviewed face-to-face. Factors associated with ordinal ratings of perception ('well managed', 'adequately managed' and 'poorly managed') were identified using ordinal logistic regression. Factors significantly associated with a reduced likelihood of 'well-managed' outbreak response ratings, adjusted for age and gender, were being involved in horse competitions/sporting events (OR = 0.48; 95% CI: 0.25-0.91), managing a horse stud (OR = 0.09; 95% CI: 0.03-0.28) and believing that another outbreak of equine influenza was highly likely in the next 5 years (OR = 0.29; 95% CI: 0.12-0.68). Possible reasons for these ratings were further investigated using content analyses. Outbreak communications and government efficiency/support were mentioned most frequently as both strengths (30% and 28%, respectively) and weaknesses (40% and 30%, respectively) of the outbreak management. To promote manager-government rapport and future compliance with disease control regulations, we recommend that outbreak communications and outbreak information systems be reviewed.

An overview of the surgical management of hepatic neuroendocrine metastases.

Neuroendocrine tumours (NET) frequently metastasise to the liver (NLM) and are associated with significant morbidity and mortality. Numerous treatment options have been implemented both for cure, and to implement disease control. Surgical treatment includes curative resection, palliative cytoreductive resection and transplantation. Complete surgical resection is only possible in a subset of people with NLMs due to excessive metastatic burden and anatomical location. Ablative therapies may be used either as an adjunct to surgery or as a primary treatment. The purpose of the following article is to summarise surgical treatment strategies in the management of patients with hepatic neuroendocrine metastases, based on the available literature.

Horse owners' biosecurity practices following the first equine influenza outbreak in Australia.

A cross-sectional study was conducted involving 759 Australian horse owners to determine their biosecurity practices and perceptions one year after the 2007 equine influenza outbreak and to investigate the factors influencing these perceptions and practices. A web link to an online questionnaire was sent to 1224 horse owners as a follow-up to a previous study to obtain information about biosecurity perceptions and practices, impacts of the 2007 EI outbreak, demographic information and information about horse industry involvement. Ordinal logistic regression analyses were conducted to determine factors associated with poor biosecurity practices. Biosecurity compliance (low, medium, high), as determined by horse owners' responses to a 16-item question on the frequency of various biosecurity measures, was used as the outcome variable in ordinal logistic regression analyses. Variables with a univariable p-value ≤0.2 were eligible for inclusion in multivariable models built using a manual stepwise approach. Variables with a p-value <0.05 in multivariable models were retained in the final model. Two potential confounders - age and gender of participants - were included in the final model irrespective of their p-values. Thirty percent of the respondents had low biosecurity compliance and were performing biosecurity practices 'not very often' or 'never'. Younger people, people with two or more children, those who were not involved with horses commercially and those who had no long-term business impacts resulting from the 2007 EI outbreak were more likely to have lower biosecurity compliance. People who were not fearful of a future outbreak of equine influenza in Australia and those who thought their current hygiene and access control practices were not very effective in protecting their horses also had poor biosecurity practices. In this observational study we identified factors associated with a group of horse owners with low levels of biosecurity compliance. As this cross-sectional study only assesses associations, the identified factors should be further investigated in order to be considered in the design of extension activities to increase horse owners' biosecurity compliance.

Pharmacogenetics of the human beta-adrenergic receptors.

The beta-adrenergic receptors (ADRBs) are cell surface receptors that play central roles in the sympathetic nervous system. Pharmacological targeting of two of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic approach for common and important diseases including asthma, hypertension and heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both in vitro and clinical disease phenotypes. More recently, interest has shifted to studies that explore potential interaction between variation in ADRBs and medications directed at these important receptors. This paper reviews the current state of knowledge and understanding of ADRB genetic variation and explores the likely direction of future studies in this area.

Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression.

Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Up-regulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis.

Ocular toxocariasis in schoolchildren.

Ocular toxocariasis in humans is typically a unilateral disease caused by second-stage larvae of the Toxocara species. Serological evidence of widespread infection in humans provides little information on clinical disease. There is only a single previous estimate of the prevalence of ocular toxocariasis (from Alabama). The present survey examined the extent of consultant-diagnosed toxocaral eye disease among a population of schoolchildren. More than 120,000 participants were surveyed by questionnaire and follow-up. Two sets of control subjects from the same school and from the same county were compared with persons who had ocular toxocariasis. The prevalence of consultant-diagnosed toxocaral eye disease was 6.6 cases per 100,000 persons when only cases regarded as definite by the consultant ophthalmologist were included. This increased to 9.7 cases per 100,000 persons when both definite and strongly suspected cases were included. Geophagia and a history of convulsion were associated with toxocaral eye disease in both of the case-control studies.

Inhibin B in boys from birth to adulthood: relationship with age, pubertal stage, FSH and testosterone.

OBJECTIVE: Inhibin B in males is produced principally by Sertoli cells under the influence of FSH and is thought to have a role in feedback regulation of FSH. The aims of our study were to investigate how inhibin B changes from birth to late adolescence in boys, to derive reference data and to explore its relation with pubertal stage, FSH and testosterone. DESIGN AND SUBJECTS: Blood samples were collected from (i) 366 boys aged 0--18 years to obtain age-related reference data; (ii) 195 boys who had full pubertal staging; and (iii) a cohort of 15 boys studied longitudinally as they approached and entered early puberty. MEASUREMENTS: Dimeric inhibin B was measured by double antibody enzyme-linked immunosorbent assay (ELISA), FSH by immunoradiometric assay (IRA) and testosterone by an extraction radioimmunoassay. RESULTS: Inhibin B was high in infant boys, decreased gradually to a nadir at 6--10 years of age, then increased rapidly in early adolescence to reach a new plateau at 12--17 years. It was detectable in all samples. Age-related reference ranges and data for calculation of SD scores are presented. In prepubertal boys, inhibin B correlated positively with age (P < 0.001), but not with FSH. Inhibin B increased progressively from pubertal stages G1 to G3 but then decreased slightly at stages G4 to G5 (P less-than-or-equal 0.01). At stage G2, inhibin B correlated positively with testosterone (P < 0.01) but not with FSH. From stage G3 onwards, inhibin B correlated inversely with FSH (P < 0.01) but lost its relationship with testosterone. In the cohort of boys studied longitudinally, inhibin B increased progressively prior to pubertal onset and further on entry into early clinical puberty (P < 0.05). Testosterone also increased over this period (P < 0.05) but FSH showed no significant change. CONCLUSIONS: The two peaks of inhibin B during infancy and early puberty appear to reflect the two periods of Sertoli cell proliferation in normal human males. During mid-childhood, a relatively constant amount of inhibin B is secreted constitutively. The early FSH-independent increase in inhibin B that precedes clinical puberty and continues to stage G2 may be stimulated by testosterone or other factors from Leydig cells. The inverse relationship between inhibin B and FSH that subsequently develops from mid-puberty onwards is consistent with the establishment of a negative feedback loop at this time.

Dimeric inhibins in girls from birth to adulthood: relationship with age, pubertal stage, FSH and oestradiol.

OBJECTIVE: Inhibin B is produced by granulosa cells in small antral follicles under the influence of FSH, whilst inhibin A is produced by larger follicles and the corpus luteum. The aims of our study were to investigate how these inhibins change from birth to late adolescence in girls, to derive reference data and to explore their relation with pubertal stage, FSH, oestradiol and each other. STUDY DESIGN AND SUBJECTS: Blood samples were collected from: (a) 345 girls aged 0--18 years to obtain age-related reference data, and (b) 80 pre-menarcheal girls with full pubertal staging, of whom 40 were on GH treatment at the time of sampling. MEASUREMENTS: Dimeric inhibins A and B were measured by double antibody enzyme-linked immunosorbent assay (ELISA), FSH by immunoradiometric assay (IRMA) and oestradiol by radioimmunoassay. RESULTS: Median inhibin B was low until age 6 years, slightly higher from 6 to 10 years, then increased from 10 to 12 years to reach a plateau from 12 to 18 years. Inhibin A was usually detectable in girls younger than 3 months but thereafter became undetectable in most samples until after age 10 years, when median levels rose progressively to 14 years, then stabilized from 14 to 18 years. Both inhibins displayed considerable scatter about the median throughout infancy, childhood and adolescence. Girls aged 0--10 years showed a positive correlation between inhibins A and B (P < 0.0001), whereas those aged 14--18 years showed an inverse relationship (P < 0.001), indicating the onset of ovulatory cycles. Age-related reference ranges and data for calculation of SD scores are presented. GH-treated girls at pubertal stage B2 (but not at B1 or B3--5) had higher inhibin B and FSH levels than untreated girls and were excluded from further analysis. Both inhibins A and B increased during puberty (P < 0.0001) and were positively correlated with each other (P < 0.01). Both inhibins were also positively correlated with FSH in pre-pubertal girls (P < 0.05) but not at pubertal stages B3--5. CONCLUSIONS: Although median levels of inhibins A and B remained low until after age 10 years in girls, the increased levels of both inhibins in individual samples, together with their positive relationship with FSH, provide further evidence of sporadic follicular development throughout infancy and childhood under the influence of FSH. The increase in both inhibins during puberty and their changing relationship with FSH are in keeping with the concept of follicular growth being dependent on the duration of FSH elevation above a critical threshold rather than the degree of elevation per se.

Use of the Internet by patients and their families to obtain genetics-related information.

OBJECTIVE: To characterize use of the Internet by patients and their families referred to general genetics clinics. PATIENTS AND METHODS: We developed a survey to assess Internet use among patients visiting urban and rural clinics in Colorado and Wyoming. One hundred eighty-nine surveys were distributed to patients and their family members visiting outpatient general genetics clinics in spring 2000. The 8-page anonymous survey instrument asked about use of the Internet to obtain genetics-related information (GRI). All participants were asked whether a physician or health professional had referred them to the Internet for GRI. Subjects who had previously used the Internet to search for GRI were asked to rate whether they considered the GRI they encountered to be accurate, inaccurate, easy to understand, confusing, or trustworthy. RESULTS: One hundred fifty-seven surveys (83%) were returned (52% urban; 48% rural). Ninety (60%) of 149 respondents were at the clinic for a new-patient visit, and 59 (40%) were follow-up visits. All respondents were older than 17 years; 141 (91%) of 155 respondents were the patient's parent or guardian. Seventy-three (47%) of 155 respondents had searched the Internet for GRI prior to their clinic visit. The patients and families themselves initiated the majority of such efforts; only 8 (5%) of 148 respondents had been referred to a site on the World Wide Web by a physician. Interestingly, 136 (92%) of 147 respondents indicated that they would be likely to visit a Web site that was recommended by a geneticist. The most compelling reasons for searching the Internet for GRI were to get information in layperson's terms (60/131 [46%]); to get information about treatment (16/131 [12%]); and to get information about genetic research (16/131 [12%]). Among respondents who reported visiting GRI Web sites, 24 (41%) of 58 agreed that information was confusing or difficult to understand, 35 (53%) of 66 agreed that information was accurate and trustworthy, and 44 (77%) of 57 agreed that using the Internet was a positive experience. CONCLUSION: Internet use among patients referred to general genetics clinics and their family members appears to be widespread. Respondents reported that they found some of the information confusing and questioned its accuracy. Referral to Web sites by physicians was reported rarely, although the majority of respondents said they would visit a Web site recommended by a genetics physician. Further studies are needed to establish the accuracy of Internet information and how best to integrate and/or accommodate the data into the genetics clinic.

The epidemiology of ocular toxocariasis.

Ocular toxocariasis damages vision and may cause blindness. It is a relatively 'new' disease, the histological changes having been described in 1950 and the causative organism identified in 1956. Many aspects of the epidemiology of toxocariasis are unclear. It is generally accepted that the usual route of entry to the eye is via the blood stream. Once the eye is invaded characteristic changes are produced with comparative sparing of the anterior segment. Species differences in susceptibility can be very marked. In Mongolian gerbils 55% of infected animals exhibit ocular lesions. Humans are fortunate in that they are far less susceptible to ocular infection. While it has been established that ocular toxocariasis is caused by Toxocara canis, the role of T. cati in this condition is still unclear. It is perhaps surprising that the prevalence of such a disease in humans should remain in doubt. However, the wide variation in the few estimates of prevalence may well be a reflection of the wide variation in exposure as evidenced by the wide variation in seroprevalence. A further factor mitigating against an identification of prevalence rates is the fact that the condition is usually unilateral. Most surveys of blindness stipulate a vision of 6/60 or less in the better eye and so toxocariasis cases go unrecorded. There is a need for surveys which identify the level of vision in both eyes.

Current perspective new insights into the molecular basis of familial dilated cardiomyopathy.

Genetic disease transmission has been identified in a significant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, as well as recent molecular genetic data, indicate the existence of several genes causing the disease. Several distinct subtypes of familial DCM have been identified. Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene. This latter gene has recently been found to be responsible for both the autosomal dominant form of DCM with subclinical skeletal muscle disease (7.7% of cases) and the familial form with conduction defects (2.6% of cases) or the autosomal dominant variant of Emery-Dreifuss muscular dystrophy. The autosomal recessive form of DCM accounts for 16% of cases and is characterized by a worse prognosis. An X-linked form of DCM (10% of cases) manifests in the adult population and is due to mutations in the dystrophin gene. In the rare infantile form of DCM, mutations in the G4.5 gene have been identified. Finally, some of the rare unclassifiable forms (7.7% of cases) may be due to mitochondrial DNA mutations. Clinical and experimental evidence based on animal models suggest that, in a large number of cases, DCMs are diseases of the cytoskeleton. However, other causes, such as alterations in regulatory elements and in signaling molecules, are possible. Moreover, other genes called modifier genes can influence the severity, penetrance, and expression of the disease, and they will be a main objective of future investigations. Familial DCM is frequent, cannot be predicted on a clinical or morphological basis and requires family screening for identification. The advances in the genetics of familial DCM can allow improved diagnosis, prevention and genetic counseling, and represent the basis for the development of new therapies.