Hyaline fibromatosis syndrome: cutaneous manifestations.
Ontology highlight
ABSTRACT:
SUBMITTER: Marques SA
PROVIDER: S-EPMC4861574 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
Publications
Hyaline fibromatosis syndrome: cutaneous manifestations.
Marques Silvio Alencar SA Stolf Hamilton Ometto HO Polizel Juliana Ocanha JO Munhoz Tânia T Brandão Marcela Calixto MC Marques Mariangela Esther Alencar ME
Anais brasileiros de dermatologia 20160401 2
Hyaline fibromatosis syndrome is the current name for clinical manifestations of diseases previously known as "infantile systemic hyalinosis" and "juvenile hyaline fibromatosis". The authors report representative clinical cases of each one of the above subtypes with emphasis on cutaneous manifestations and difficulties for early diagnosis in this syndrome, essentially of multidisciplinary approach. ...[more]
Similar Datasets
Project description:Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs. It represents a disease spectrum with infantile systemic hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF) being the mild form. Dermatologic manifestations include thickened skin, perianal nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on the scalp, hyperpigmented plaques over the metacarpophalangeal joints and malleoli, and joint contractures. ISH shows a severe visceral involvement, recurrent infections, and early death. We report a case of 2.5-year-old female patient who presented with HFS who had overlapping features of both ISH and JHF. To the best of our knowledge, very few cases of HFS have been reported in Indian literature till date.
| S-EPMC5029258 | biostudies-literature
Project description:BackgroundHyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2 which leads to loss of function of the transmembrane protein anthrax toxin receptor 2. It is distinguished by characteristic skin lesions, gingival hyperplasia, joint and bone disease, and systemic involvement.MethodsBased on the case of an 11-year-old female patient with typical features of hyaline fibromatosis syndrome and the underlying pathogenic compound heterozygote variants in ANTXR2 we discuss the genetic and clinical aspects of hyaline fibromatosis syndrome.ResultsThe novel mutation in ANTXR2 (c.1223T>C, p.Leu408Pro variant) seems to allow for a protracted course of the disease.ConclusionOur findings add to the phenotypic, genetic, and biochemical spectrum of hyaline fibromatosis syndrome.
| S-EPMC7284039 | biostudies-literature
Project description:Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), a severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and severe painful joint contracture. Here we show that CMG2 is an important regulator of collagen VI homoeostasis. CMG2 loss of function promotes accumulation of collagen VI in patients, leading in particular to nodule formation. Similarly, collagen VI accumulates massively in uteri of Antxr2-/- mice, which do not display changes in collagen gene expression, and leads to progressive fibrosis and sterility. Crossing Antxr2-/- with Col6a1-/- mice leads to restoration of uterine structure and reversion of female infertility. We also demonstrate that CMG2 may act as a signalling receptor for collagen VI and mediates its intracellular degradation.
| S-EPMC5472780 | biostudies-literature
Project description:INTRODUCTION: Juvenile hyaline fibromatosis and infantile systemic hyalinosis are variants of the same autosomal recessive syndrome; hyaline fibromatosis syndrome, characterized by papulonodular skin lesions, gingival hypertrophy, flexion contractures of joints, osteolytic bone lesions and stunted growth. Infantile systemic hyalinosis is distinguished from juvenile hyaline fibromatosis by its more severe phenotype, which includes hyaline deposits in multiple organs, recurrent infections and death within the first two years of life.Hyaline fibromatosis syndrome is due to mutations of the gene-encoding capillary morphogenesis protein 2 (CMG2). Cases have been reported in different countries but to the best of our knowledge, this is the first reported Moroccan patient with hyaline fibromatosis syndrome and carrying the CMG2 mutation. CASE PRESENTATION: We report the case of an eight-year-old Moroccan male patient with typical features of hyaline fibromatosis syndrome: multiple recurring subcutaneous tumors, gingival hypertrophy, joint contractures and other anomalies carrying a homozygous mutation in the CMG2 gene. The identification of the mutation in our patient allowed us to do a presymptomatic diagnosis in our patient's sister, a two-day-old newborn, who is carrying the familial mutation in the heterozygous state. Early recognition of this condition is important for genetic counseling and early treatment. CONCLUSIONS: Hyaline fibromatosis syndrome might be underdiagnosed. Molecular diagnosis will help clinicians and geneticists, firstly to conduct genetic counseling, prenatal diagnosis and early treatment, and secondly to gain better understanding of the disease and genotype-phenotype correlations.
| S-EPMC4158768 | biostudies-literature
Project description:BackgroundHyaline fibromatosis syndrome (HFS) is a rare clinical condition in which bi-allelic variants in ANTXR2 are associated with extracellular hyaline deposits. It manifests as multiple skin nodules, patchy hyperpigmentation, joint contractures and severe pain with movement. HFS shows some clinical overlap to Farber disease (FD), a recessive lysosomal storage disorder.ResultsWe here present the largest cohort of independent, genetically confirmed HFS cases reported to date: in 19 unrelated index patients, we identified ten distinct homozygous ANTXR2 mutations, three of which are novel frame-shift variants. The associated clinical data are consistent with the previous hypothesis of non-truncating variants in the terminal exons 13-17 to confer rather mild phenotypes. The novel observation of gender-dependent disease manifestation in our cohort received support from a meta-analysis of all previously published cases. Untargeted blood-based metabolomics revealed patient samples to be biochemically distinct from control samples. Numerous potential HFS biomarker metabolites could thus be identified. We also found metabolomics profiles of HFS patients to highly overlap with those from FD patients.ConclusionsOur study extends the mutational spectrum for HFS, suggests gender-dependency of manifestation, and provides pilot metabolomics data for biomarker identification and a better pathomechanistic understanding of the disorder.
| S-EPMC6712857 | biostudies-literature
Project description:BACKGROUND:Hyaline fibromatosis syndrome (HFS) is a rare heritable multi-systemic disorder with significant dermatologic manifestations. It is caused by mutations in ANTXR2, which encodes a transmembrane receptor involved in collagen VI regulation in the extracellular matrix. Over 40 mutations in the ANTXR2 gene have been associated with cases of HFS. Variable severity of the disorder in different patients has been proposed to be related to the specific mutations in these patients and their location within the gene. CASE PRESENTATION:In this report, we describe four cases of HFS from consanguineous backgrounds. Genetic analysis identified a novel homozygous frameshift deletion c.969del (p.Ile323Metfs*14) in one case, the previously reported mutation c.134 T?>?C (p.Leu45Pro) in another case, and the recurrent homozygous frameshift mutation c.1073dup (p.Ala359Cysfs*13) in two cases. The epidemiology of this latter mutation is of particular interest, as it is a candidate for inhibition of nonsense-mediated mRNA decay. Haplotype analysis was performed to determine the origin of this mutation in this consanguineous cohort, which suggested that it may develop sporadically in different populations. CONCLUSIONS:This information provides insights on genotype-phenotype correlations, identifies a previously unreported mutation in ANTXR2, and improves the understanding of a recurrent mutation in HFS.
| S-EPMC5970508 | biostudies-literature
Project description:Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2KO organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE.
| S-EPMC7662532 | biostudies-literature
Project description:BackgroundHyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions.MethodsWe describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents.ResultsA mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted.ConclusionsThe main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases.
| S-EPMC5244738 | biostudies-literature
Project description:BackgroundMutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia. Many patients with DOCK8 deficiency were previously thought to have a variant of Job's syndrome. Distinguishing between DOCK8 deficiency and Job's syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging. The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes.ObservationsTwenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCK8 were evaluated. Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections. Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in 5 patients during adolescence and young adulthood.ConclusionsDOCK8 deficiency and Job's syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses. However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job's syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia.
| S-EPMC4103903 | biostudies-literature
Project description:Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition characterized by multiple subcutaneous nodular tumors, gingival fibromatosis, flexion contractures of the joints, and an accumulation of hyaline in the dermis. We performed a genomewide linkage search in two families with JHF from the same region of the Indian state of Gujarat and identified a region of homozygosity on chromosome 4q21. Dense microsatellite analyses within this interval in five families with JHF who were from diverse origins demonstrate that all are compatible with linkage to chromosome 4q21 (multipoint LOD score 5.5). Meiotic recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and D4S395.
| S-EPMC378553 | biostudies-literature