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Background: Cutaneous neurofibromas (cNFs) are a major cause of disfigurement in patients with Neurofibromatosis Type 1 (NF1). However, clinical trials investigating cNF treatments lack standardised outcome measures to objectively evaluate changes in cNF size and appearance. 3D imaging has been proposed as an objective standardised outcome measure however various systems exist with different features that affect useability in clinical settings. The aim of this study was to compare the accuracy, precision, feasibility, reliability and accessibility of three imaging systems. Materials and methods: We compared the Vectra‐H1, LifeViz‐Micro and Cherry‐Imaging systems. A total of 58 cNFs from 13 participants with NF1 were selected for imaging and analysis. The primary endpoint was accuracy as measured by comparison of measurements between imaging systems. Secondary endpoints included reliability between two operators, precision as measured with the average coefficient of variation, feasibility as determined by time to capture and analyse an image and accessibility as determined by cost. Results: There was no significant difference in accuracy between the three devices for length or surface area measurements (p > 0.05), and reliability and precision were similar. Volume measurements demonstrated the most variability compared to other measurements; LifeViz‐Micro demonstrated the least measurement variability for surface area and image capture and analysis were fastest with LifeViz‐Micro. LifeViz‐Micro was better for imaging smaller number of cNFs (1–3), Vectra‐H1 better for larger areas and Cherry for uneven surfaces. Conclusions: All systems demonstrated excellent reliability but possess distinct advantages and limitations. Surface area is the most consistent and reliable parameter for measuring cNF size in clinical trials. [ABSTRACT FROM AUTHOR]

The skin manifestations of neurofibromatosis 1 significantly reduce health‐related quality‐of‐life. However, data on the utility of existing surveys in capturing neurofibromatosis 1 skin treatment outcomes are lacking. This quantitative study examined the relationship between clinician‐rated severity and visibility and patient‐rated itch and quality‐of‐life (QoL) to (1) establish baseline levels of skin‐ and condition‐specific‐related QoL, itch, depression and anxiety; (2) identify patient concerns to inform the development and evaluation of skin interventions; and (3) compare the sensitivity of different QoL measures. Validated scales included Skindex‐29, Dermatology Life Quality Index (DLQI), Neurofibromatosis 1‐adult quality‐of‐life (NF1‐AdQOL) questionnaire, and the Hospital Anxiety and Depression Scale (HADS). We recruited 100 participants (response rate: 95%). Of these, 42% reported itch and 23% had probable clinical anxiety. Our cohort had higher levels of anxiety and total HADS scores compared to a control population. Using multivariate regression analysis, increasing visibility significantly predicted poorer QoL using the Skindex‐29, NF1‐AdQOL, and DLQI (p < 0.05); and itch significantly predicted worse QoL in Skindex‐29 and NF1‐AdQOL (p < 0.05). The highest mean scoring questions in Skindex‐29 and NF1‐AdQOL concerned worry about worsening skin disease and embarrassment. The highest mean scoring questions in DLQI were regarding itch, pain, and embarrassment. Items asking specifically about cutaneous neurofibromas (cNF) scored higher than comparable skin‐specific questions (t‐test p value <0.05). In summary, this study provides insights into the factors contributing to impaired QoL, anxiety, and mood in NF1 patients with cutaneous neurofibromas. Key factors identified for use in cNF measures include visibility, itch, anxiety, embarrassment, fears of worsening skin disease, and cNF‐specific questions. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis 1 (NF1) is a common cancer predisposition syndrome. Affected individuals require lifelong surveillance and often suffer progressive disfigurement due to cutaneous neurofibromas. The aim of this research was to characterize health concerns and quality of life (QOL) in a population cohort. Methods: An online survey was completed by 68 adults and 32 parents of children with NF1, and 60 controls. The survey included the Skindex‐29 QOL scale, 5D‐itch scale, and additional health questions. Results: Frequency of itch was high in children (50%) and adults (69%), with most expressing interest in treatment for itch. The presence of itch and increased visibility of NF1 were predictors of poorer QoL. Many adults (53%) and parents (44%) desired access to treatment to improve cosmetic appearance. Muscle weakness/tiredness was also prevalent amongst (60–70%) adults and children with NF1. Two‐thirds of adults with NF1 reported limited awareness of NF1 services and poor knowledge of surveillance, particularly breast screening in young women. Conclusion: This study highlights the impact of NF1‐related itch and visibility in adults and children with a need for cosmetic and itch treatment. The findings emphasize a need for strategies to promote awareness, and access to management and treatment of NF1 in adults. [ABSTRACT FROM AUTHOR]

Monogenic rare disorders contribute significantly to paediatric morbidity and mortality, and elucidation of the underlying genetic cause may have benefits for patients, families and clinicians. Advances in genomic technology have enabled diagnostic yields of up to 50% in some paediatric cohorts. This has led to an increase in the uptake of genetic testing across paediatric disciplines. This can place an increased burden on paediatricians, who may now be responsible for interpreting and explaining test results to patients. However, genomic results can be complex, and sometimes inconclusive for the ordering paediatrician. Results may also cause uncertainty and anxiety for patients and their families. The paediatrician's genetic literacy and knowledge of genetic principles are therefore critical to inform discussions with families and guide ongoing patient care. Here, we present four hypothetical case vignettes where genomic testing is undertaken, and discuss possible results and their implications for paediatricians and families. We also provide a list of key terms for paediatricians. [ABSTRACT FROM AUTHOR]

The Genetic Information System (GIS) is an Australian database of family genetic information. This health information technology system has been used by all 31 publicly operated clinical genetics services across New South Wales (NSW) and the Australian Capital Territory (ACT) for over a decade. As these services are separated geographically, the linkage engendered by the GIS facilitates the services to operate as a virtual state‐wide service. This study aimed to explore the views of genetic counselors, patients, and carers on the use and storage of family genetic information in the GIS. Data were collected using audio‐recorded semi‐structured telephone interviews with genetic counselors experienced with using the GIS and focus groups with past patients/carers of the services. Using thematic analysis, four themes were identified from genetic counselor participant interviews (n = 12): (a) Shared information is valuable; (b) inconsistent data entry provides a challenge; (c) perceived need for the GIS to be current and integrated with other health systems; and (d) future challenges and strategies for the GIS. Three themes were identified following three focus groups with consumer participants (n = 14): (a) access to family genetic information provides a 'clearer picture'; (b) support, but caution, concerning use of information for relatives' health care; and (c) stewardship of family information. Genetic counselors and consumers identified similar advantages and privacy concerns regarding the sharing of family genetic information and all participants wanted patients/carers to be better informed about the GIS early in the genetic counseling process. Consumers were reassured by genetics health professionals' stewardship of their information, but surprised the GIS was not available nationally or for private geneticists or certain non‐genetic specialists. These findings may inform further development of the GIS and other clinical genetic databases and lead to increased patient/carer knowledge through education and resource development. [ABSTRACT FROM AUTHOR]

Genomic testing for a genetic diagnosis is becoming standard of care for many children, especially those with a syndromal intellectual disability. While previously this type of specialised testing was performed mainly by clinical genetics teams, it is increasingly being 'mainstreamed' into standard paediatric care. With the introduction of a new Medicare rebate for genomic testing in May 2020, this type of testing is now available for paediatricians to order, in consultation with clinical genetics. Children must be aged less than 10 years with facial dysmorphism and multiple congenital abnormalities or have global developmental delay or moderate to severe intellectual disability. This rebate should increase the likelihood of a genetic diagnosis, with accompanying benefits for patient management, reproductive planning and diagnostic certainty. Similar to the introduction of chromosomal microarray into mainstream paediatrics, this genomic testing will increase the number of genetic diagnoses, however, will also yield more variants of uncertain significance, incidental findings, and negative results. This paper aims to guide paediatricians through the process of genomic testing, and represents the combined expertise of educators, clinical geneticists, paediatricians and genomic pathologists around Australia. Its purpose is to help paediatricians navigate choosing the right genomic test, consenting patients and understanding the possible outcomes of testing. [ABSTRACT FROM AUTHOR]

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies. [ABSTRACT FROM AUTHOR]

The complications of neurofibromatosis type 1 (NF1) are widespread, unpredictable and variable and each person's experience of this disorder is unique. However, few studies have addressed the impact of NF1 from an individual's perspective. This qualitative study aims to identify the ways in which NF1 impacts upon affected Australian adults. Sixty adults with NF1, with a range of disease severity and visibility participated in a semi-structured interview about the ways in which NF1 impacted upon their life and health. Data were analyzed using grounded theory methodology. Results indicated that NF1 impacts upon affected adults in five major ways: 1) cosmetic burden of disease 2) learning difficulties 3) concerns about the risk of passing NF1 to offspring 4) uncertain disease progression, and 5) pain. Participants identified the aspects of NF1 that bothered them the most, creating a hierarchy of NF1 concerns within the cohort. Importantly, mildly affected adults shared many of the same concerns as those more severely affected. This study enhances our current understanding of the impact of NF1 in adulthood, and augments existing recommendations for the care of these patients. [ABSTRACT FROM AUTHOR]

Internationally, Tay- Sachs disease ( TSD) preconception screening of Ashkenazi Jewish ( AJ) individuals and couples has led to effective primary prevention of TSD. In Australia, adolescent preconception genetic screening programs operate mainly in Jewish community high schools. These existing programs offer an effective means of primary prevention of TSD, are cost effective and safe. However, in the broader Australian community TSD screening is not systematically performed and cases still occur in unscreened AJ individuals. In order to improve the effectiveness of Australian screening, there is a need for definitive guidelines for healthcare professionals to facilitate extension of the proven benefits of preconception TSD screening to all AJ individuals at risk. We performed a systematic review of the relevant literature relating to AJ pre-conception and antenatal screening for TSD. The evidence was assessed using an established National Health and Medical Research Council evidence grading system. Evaluations of efficacy of TSD screening programs design and execution, cost-benefit and cost-utility health economic evaluation, and population outcomes were undertaken. The results have been used to propose a model for universal AJ TSD preconception and antenatal screening for the primary care setting. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the ophthalmic features and causes of visual loss in a cohort of Melanesians living in New Caledonia with nanophthalmos. Methods: In this observational study, axial length, visual acuity (VA), cycloplegic autorefraction were assessed and dilated fundus examination was performed. Visual impairment was defined as VA < 6/12 in the better eye, hypermetropia as >+1.0 dioptre (D), astigmatism as ≥1.0 D and anisometropia as ≥1.0 D difference between both eyes. Unilateral amblyopia was defined as at least a two-line difference in VA between both eyes and bilateral amblyopia as VA < 6/12 in both eyes which was not adequately explained by refractive error and macular folds. Results: Seventeen community-dwelling participants (aged 1.1–45.3 years) with short axial length (range from 16.1 to 21.6 mm) were identified. Of the 17 subjects, 14 were found to have crowded optic discs, three with papillomacular folds, three with a papillomacular band and three with macular radial folds. Further, all subjects demonstrated bilateral hypermetropia (range from +1.3 D to +15.1 D). A high proportion of subjects had astigmatism (12) and anisometropia (nine) in at least one eye. Visual impairment was found in nine subjects: five bilateral and four unilateral. Causes of visual impairment included amblyopia (seven), ametropia (seven) and macular folds (two). Amblyopia was attributed to several factors, including hypermetropia, anisometropia, astigmatism and esotropia. Conclusions: In this sample of Melanesians with nanophthalmos, a spectrum of ophthalmic features that was consistent with intraocular crowding was found. Over half of the subjects were visually impaired, mostly due to amblyopia and ametropia. Further characterization of the underlying genetic cause of nanophthalmos in this cohort will be the focus of future studies. [ABSTRACT FROM AUTHOR]