Karin Soares Gonçalves Cunha

Bio: Karin Soares Gonçalves Cunha is an academic researcher from Federal Fluminense University. The author has contributed to research in topics: Neurofibromatosis & Neurofibroma. The author has an hindex of 12, co-authored 62 publications receiving 511 citations.

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

Abstract: Neurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000-3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations affecting p.Arg1809 and a single amino acid deletion p.Met922del. Both variants predispose to a distinct mild NF1 phenotype with neither externally visible cutaneous/plexiform neurofibromas nor other tumors. Here, we report 162 individuals (129 unrelated probands and 33 affected relatives) heterozygous for a constitutional missense mutation affecting one of five neighboring NF1 codons-Leu844, Cys845, Ala846, Leu847, and Gly848-located in the cysteine-serine-rich domain (CSRD). Collectively, these recurrent missense mutations affect ∼0.8% of unrelated NF1 mutation-positive probands in the University of Alabama at Birmingham (UAB) cohort. Major superficial plexiform neurofibromas and symptomatic spinal neurofibromas were more prevalent in these individuals compared with classic NF1-affected cohorts (both p < 0.0001). Nearly half of the individuals had symptomatic or asymptomatic optic pathway gliomas and/or skeletal abnormalities. Additionally, variants in this region seem to confer a high predisposition to develop malignancies compared with the general NF1-affected population (p = 0.0061). Our results demonstrate that these NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation. A genotype-phenotype correlation at the NF1 region 844-848 exists and will be valuable in the management and genetic counseling of a significant number of individuals.

Neurofibromatosis type I with periodontal manifestation. A case report and literature review.

Abstract: The term neurofibromatosis (NF) is used for a group of genetic disorders that primarily affect the cell growth of neural tissues. Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is the most common type of NF and accounts for about 90% of all cases. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3,000 births. The expressivity of NF1 is extremely variable, with manifestations ranging from mild lesions to several complications and functional impairment. Oral manifestations can be found in almost 72% of NF1 patients. A case of a NF1 patient with a gingival neurofibroma in the attached gingiva of the lingual aspect of the lower central incisors is presented. The lesion was nodular, with sessile base, non-ulcerated, non-painful, with normal colour and measured 1 cm in diameter. An excisional biopsy of the oral lesion was performed. Histopathological and immunohistochemical analysis confirmed the clinical hypothesis of neurofibroma. Because NF1 is one of the most common genetic diseases and oral manifestations are very common, dentists should be aware of the characteristics of this disease.

Identification of growth hormone receptor in localised neurofibromas of patients with neurofibromatosis type 1.

Abstract: Background: The hallmark of neurofibromatosis type 1 (NF1) is the development of multiple neurofibromas. Solitary neurofibroma may occur in an individual who does not have NF1, but multiple neurofibromas tend to develop only in those with NF1. It has been suggested that hormones may influence the neurofibromas of patients with NF1. The evidence that hormones may influence the growth of neurofibromas comes mainly from the observation that localised neurofibromas of patients with NF1 commonly grow during puberty and pregnancy. Because growth hormone (GH) concentrations increase during puberty, it is possible that GH influences the growth of these tumours. Aims: To investigate the presence of GH receptors (GHRs) in neurofibromas. Methods: By means of immunohistochemistry, the presence of GHRs was investigated in two groups of patients: 16 patients without NF1 with solitary neurofibromas (group A) and 10 patients with NF1 with localised neurofibromas (group B). Results: Six of the 16 patients in group A had neurofibromas that were immunopositive for GHR, whereas nine of the 10 patients in group B were immunopositive. Conclusions: Most patients with NF1 have localised neurofibromas that express GHR. This suggests that GH may play some role in the development of localised neurofibromas in patients with NF1.

Prevalence of oral lichen planus in Brazilian patients with HCV infection.

Abstract: Objective The objective of this investigation was to assess the prevalence of oral lichen planus (OLP) in Brazilian patients infected with hepatitis C virus (HCV) from the state of Rio de Janeiro. Study design The study group consisted of 134 patients with HCV infection. The control group consisted of 95 individuals. All patients were physically examined for evidence of OLP. The diagnosis of OLP was established on the basis of usual clinical features and histological findings. Results The prevalence of OLP was 1.5% in patients with HCV infection and 1.1% in the control group. There was no statistically significant difference between the 2 groups (P = .63). Conclusion Our findings indicate that there is no association between OLP and HCV infection in Brazilian patients from the state of Rio de Janeiro.

Neurofibromatoses: part 1 ? diagnosis and differential diagnosis

Abstract: Neurofibromatoses (NF) are a group of genetic multiple tumor growing predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors and cutaneous signs. They affect nearly 80 thousand of Brazilians. In recent years, the increased scientific knowledge on NF has allowed better clinical management and reduced complication morbidity, resulting in higher quality of life for NF patients. In most cases, neurology, psychiatry, dermatology, clinical geneticists, oncology and internal medicine specialists are able to make the differential diagnosis between NF and other diseases and to identify major NF complications. Nevertheless, due to its great variability in phenotype expression, progressive course, multiple organs involvement and unpredictable natural evolution, NF often requires the support of neurofibromatoses specialists for proper treatment and genetic counseling. This Part 1 offers step-by-step guidelines for NF differential diagnosis. Part 2 will present the NF clinical management.

Syndromes of the Head and Neck

Abstract: British authors are the natural heirs to Charles Dickens and Graham Greene.) Nevertheless there are advantages to British readers in a British book especially, for instance, in the chapter on social paediatrics and occasionally as regards therapeutics. The new Forfar and Arneil is, like its predecessors, a good book. There are many new authors and much of it has been completely rewritten. Each chapter has a long list of references, many of them to further reading in books and important 'landmark' papers rather than to very recent original work, and that seems appropriate for a textbook of this nature. It is up to date, including references to topics such as oesophageal pH monitoring in gastrooesophageal reflux, the value of steroids in bacterial meningitis, a full account of the peroxisomal disorders, the significance of dystrophin in muscular dystrophy, the importance of vitamin A in reducing mortality in third world countries, and the use of sumatriptan in migraine and of vigabatrin and lamotrigine in epilepsy. Surprisingly, neither in this nor in Nelson's textbook could I find any reference to Angelman's syndrome. Some topics chosen at random such as Prader-Willi syndrome or haemolytic uraemic syndrome were discussed more fully in the British textbook. There is a surprising omission, however, and that is the chapter on disorders ofear, nose, and throat. Adenoids, glue ear or secretory otitis media, tonsillitis, and tonsillectomy have all been dropped from the index and deafness is dealt with in the chapter on neurology. If you look up 'tonsils' you will be referred to any entry which reads: 'Tonsils: size, presence of infection, exudate, pitting, peritonsillar swelling?'. The index entry 'ear, nose and throat problems' refers to a brief account of such problems in children with cleft palate. It is one of those crazy facts of modern life that the American book costs £60, the British £125. Who will read this new edition? I shall, and I suppose many other consultant paediatricians will also use it as a standard reference book. Undergraduate students will need a more compact text for their basic reading but should use it to look up specific topics, and doctors studying for the MRCP in paediatrics should make a systematic assault on it to provide them with a personal database to be supplemented by journals and monographs. As a textbook of British paediatrics it has no competition and it remains an excellent work of reference which must be available in all paediatric departments in Britain, but the absence of the chapter on ear, nose, and throat disorders must surely be an error and there is clearly a marketing problem for British publishers faced with American competition. If we want British textbooks, and I would not like to think that the time will be forced upon us when we shall have no choice, then it looks as if we must be prepared to pay for the privilege. DOUG ADDY Consultant paediatrician

Deep intronic mutations and human disease.

Abstract: Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a substantial proportion of patients, sequence information restricted to exons and exon-intron boundaries fails to identify the genetic cause of the disease. Here we review evidence from mRNA analysis and entire genomic sequencing indicating that pathogenic mutations can occur deep within the introns of over 75 disease-associated genes. Deleterious DNA variants located more than 100 base pairs away from exon-intron junctions most commonly lead to pseudo-exon inclusion due to activation of non-canonical splice sites or changes in splicing regulatory elements. Additionally, deep intronic mutations can disrupt transcription regulatory motifs and non-coding RNA genes. This review aims to highlight the importance of studying variation in deep intronic sequence as a cause of monogenic disorders as well as hereditary cancer syndromes.

Syndromes of the Head and Neck.

Abstract: The title of this volume is, in a sense, a misnomer because there is a wealth of information on body areas other than the head and neck. Nevertheless, the authors use clinical signs and symptoms which are found in the structures of the head and neck as a jumping-off point for the recognition of conditions which have been identified as specific syndromes. There are 103 chapters, each devoted to a given syndrome, arranged in alphabetical order. A detailed index complements the alphabetized table of contents, and an appendix provides a limited series of tables relating to development and maldevelopment of structures of the head and neck. Tables for normal chronologic development of deciduous and permanent teeth unfortunately do not take advantage of the more recent information such as provided by Moorrees et al ( J Dent Res 42:1490, 1963). The text is supported by a large number of excellent illustrations including

Hepatitis C virus infection and lichen planus: a systematic review with meta-analysis.

Abstract: Oral Diseases (2010) 16, 601–612 Objective: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations including mixed cryoglubulinemia, non–Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta-analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection. Materials and Method: Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model. Results and Conclusions: Thirty-three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta-analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58–6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84–10.86). Sub-analyses indicated that variability of HCV/lichen planus association seemed only partially depending on geographic effect.