Prognostic factors for wellbeing in patients with hyaline fibromatosis syndrome.

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a congenital disorder characterized by subcutaneous skin nodules, congenital multiple arthrogryposis, gingival hyperplasia, and chronic pain. The intellectual ability of patients with HFS is generally normal. This syndrome arises from variants of ANTXR2. Thus far, about 100 cases have been reported but few of these were reported from Japan. METHODS: This study reports five additional Japanese patients with genetically confirmed HFS, from unrelatd families, and discusses the clinical course and quality of life of these patients. RESULTS: At our last visit the ages of the patients were 3-19 years (the median age was 5 years). All the patients had arthrogryposis, skin nodules, and gingival hyperplasia, and four patients had chronic pain, all of which are distinctive, clinical characteristics of HFS. Four of the patients (80%) had pruritic skin nodules, and three experienced sleep disruptions due to pruritis. The visceral complications are an index of HFS severity. One patient in the present cohort had a mucosal abnormality without any gastrointestinal symptoms. CONCLUSION: Preventive and routine management of pruritis caused by skin nodules should be shared with the patient's family. Even asymptomatic patients might have endoscopic finding, which would be a soft marker that could predict the development of protein losing enteropathy.

Hypercalcemia as a rare presentation of hyaline fibromatosis syndrome from different Sudanese families: two case reports.

BACKGROUND: Hyaline fibromatosis syndrome is a rare progressive autosomal recessive connective tissue disorder caused by a mutation in the ANTXR2/CMG2 gene. According to its severity, patients may present with skin nodules or visceral infiltration, which carries a poor prognosis. Hypercalcemia has not been reported as a presenting feature of this syndrome. Stimulation of osteoclasts by inflammatory factors and immobilization--induced hypercalcemia have played role in the pathophysiology. To our knowledge, this is the first report of hypercalcemia-associated hyaline fibromatosis syndrome. CASE PRESENTATION: Here, we describe cases of two Sudanese patients, a boy aged 9 months and a girl aged 3.5 years with hypercalcemia as an associated presenting feature of hyaline fibromatosis syndrome. Other features include gingival hypertrophy, painful joint swellings, and restriction of movement, which was misdiagnosed as juvenile rheumatoid arthritis. Workup showed normal phosphate, normal to mildly elevated parathyroid hormone, low vitamin D 25. Genetic testing confirmed the mutation of the ANTXR2/CMG2 gene. Both patients responded well to medical therapy for hypercalcemia, but one of them with the severe form of juvenile hyaline fibromatosis died due to sepsis, while the other one has maintained normocalcemic status. CONCLUSIONS: These cases highlight the rare presentation of this syndrome and reflect the importance of biopsy and genetic testing in reaching the diagnosis, especially when the clinical presentation can mimic other inflammatory bone disorders. Calcium levels should be checked in such cases.

Femur fracture in a paediatric patient with hereditary hyaline fibromatosis syndrome.

An 18-month-old girl with hereditary hyaline fibromatosis syndrome (HHFS) and fixed flexion contractures presented with an oblique femur fracture, following a fall out of her mother's arms. The fracture was abutting intramedullary hyaline lesions. Due to her condition, balanced traction was impossible to apply. The authors report effective treatment of her injury using a non-operative approach in an early hip spica, over a 4-week period. There was no evidence of delayed osseous healing. Early spica application could be used as a definitive management option in children with femur fractures and fixed flexion contractures in future. This case emphasises the need for preventative measures to support bone health in patients with HHFS.

Anesthetic Management of an Adult Patient With Hyaline Fibromatosis Syndrome Undergoing Laparoscopic Colectomy: A Case Report.

Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive disorder characterized by hyaline fibrous depositions in the skin and internal organs. Contractured joints and gingival hypertrophy make airway management difficult in patients with HFS, while trunk deformities complicate surgical positioning. A 56-year-old woman with HFS underwent laparoscopic colectomy for sigmoid colon cancer. Her airway was secured by awake fiberoptic intubation, and general anesthesia was maintained uneventfully. This report discusses the oldest reported patient with HFS and is the first to describe the management of epidural anesthesia in a patient with HFS.

Hyaline fibromatosis syndrome: Clinical update and phenotype-genotype correlations.

Hyaline fibromatosis syndrome (HFS) is the unifying term for infantile systemic hyalinosis and juvenile hyaline fibromatosis. HFS is a rare autosomal recessive disorder of the connective tissue caused by mutations in the gene for anthrax toxin receptor-2 (ANTXR2). It is characterized by abnormal growth of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. We reviewed the 84 published cases and their molecular findings, aiming to gain insight into the clinical features, prognostic factors, and phenotype-genotype correlations. Extreme pain at minimal handling in a newborn is the presentation pattern most frequently seen in grade 4 patients (life-limiting disease). Gingival hypertrophy and subcutaneous nodules are some of the disease hallmarks. Though painful joint stiffness and contractures are almost universal, weakness and hypotonia may also be present. Causes of death are intractable diarrhea, recurrent infections, and organ failure. Median age of death of grade 4 cases is 15.0 months (p25-p75: 9.5-24.0). This review provides evidence to reinforce the previous hypothesis that missense mutations in exons 1-12 and mutations leading to a premature stop codon lead to the severe form of the disease, while missense pathogenic variants in exons 13-17 lead to the mild form of the disease. Multidisciplinary team approach is recommended.

Infantile Systemic Hyalinosis Complicated with Right Atrial Thrombus and Pericardial Effusion in an Infant.

Infantile systemic hyalinosis (ISH) is a rare multisystem fatal autosomal recessive disorder that involves widespread deposition of hyaline on connective tissues and certain internal organs. The major manifestations include painful articular contractures, hyperpigmentation, subcutaneous nodules, gingival hypertrophy, failure to thrive secondary to protein-losing enteropathy, and osteolytic bone lesions. In this paper, we report a 12-month-old girl with ISH presenting with recurrent diarrhea, failure to thrive, and refractory infections. A molecular study identified a homozygous missense mutation, c.134T > C; p.L45P, in exon 1 of the anthrax toxin receptor 2 (ANTRX2) gene. Our patient passed through an eventful course that included septic shock, central line infections, right atrial thrombosis, and pericardial effusion. She incurred acute bronchiolitis due to respiratory syncytial virus infection, which led to her death. In conclusion, this case report highlights that severe and life-threatening morbidities and complications can be encountered in ISH, to which some management options can be applied.

Unusual cause for gum hypertrophy and skin nodules in a child.

Juvenile hyaline fibromatosis (JHF) is a rare progressive autosomal recessive disease that is characterised by papulonodular skin lesions, soft tissue masses, joint contractures, gingival hypertrophy and osteolytic bone lesions. We present an 18-month-old boy with JHF. This case demonstrates that JHF should be considered in the differential diagnosis when multiple subcutaneous nodules are observed in the face, head and neck. Gum hypertrophy with palatal nodules is unusual in JHF.

Juvenile hyaline fibromatosis: a case report.

Juvenile hyaline fibromatosis is a rare, hereditary disease with distinct clinical and histopathological features. Clinically, it presents with gingival hypertrophy, pappulonodular skin lesions and joint contractures. Bone involvement is usually an uncommon finding. We report a case of a 2-year-old patient, daughter of consanguineous parents, who presented since the age of 2 months with impairment of mental development, multiple joint contractures, motion limitation and nodules on the scalp. The calvarian lesions were surgically removed, and histopathological examination concluded to juvenile hyaline fibromatosis.

Three years old child with juvenile hyaline fibromatosis presenting with rectal bleeding.

Juvenile hyaline fibromatosis is a rare inherited autosomal recessive disorder which is caused by mutation of CMG2 gene on chromosome 4q21. Mutation of this gene protein can disrupt the formation of basement membranes. Hyalinization of various body tissues like skin, joints, and bones leads to development of skin papules, gingival hyperplasia, osteolytic lesions in bones, and joint contractures. We had a case of a 3 years old female child with Juvenile Hyaline Fibromatosis who presented with rectal bleeding. She had a bleeding mucocutaneous lesion in anal canal along with papullonodular lesions on the face, gingival hypertrophy and flexion contractures of small joints of hands and feet. Excision of the anal lesion revealed histopathological features of Juvenile Hyaline Fibromatosis.

Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disease. Typically, ISH patients present with progressive painful joint contractures, intractable diarrhea, hyperpigmented skin lesions, and peri-anal fleshy nodules. We report a case of a 19-month-old male child with atypical ISH presentation. His main clinical finding was protein-losing enteropathy due to intestinal lymphangectasia. This report is intended to enhance awareness about the gastrointestinal tract presentation of ISH.

Micofenolato de mofetilo en cuatro pacientes con síndrome nefrótico e hialinosis segmentaria y focal / Mycophenolate mofetil in four patients with nephrotic syndrome and focal segmental glomerulosclerosis

Describimos los casos de cuatro pacientes con síndrome nefrótico(SN) diagnosticados, mediante biopsia, de hialinosis segmentaria y focal (tres de ellos corticodependientes, con múltiples recaídas a pesar del tratamiento con corticoides e inmunosupresores, y uno de ellos corticorresistente), en los que se inició tratamiento con micofenolato de mofetilo (MMF).Durante el tratamiento se registraron los niveles plasmáticos de ácido micofenólico de forma mensual. Se controlaron en la consulta la función renal (mediante la fórmula de Schwartz) y la proteinuria, así como los posibles efectos secundarios de la medicación. Nuestros pacientes presentaron sus primeros brotes de SNa edades similares (2-3 años). La edad de inicio del fármaco fue en dos pacientes antes de los 4 años y en los otros dos después de los 12 años. A pesar de usar dosis supraterapéuticas (mediana de los niveles de 5,625), todos los pacientes han mantenido una evolución clínico-analítica satisfactoria, con rangos de función renal y proteínas totales normales, sin presentar ninguna recaída (remisión total) o efectos secundarios (salvo gastrointestinales leves) ni precisar otras terapias asociadas. La duración media del tratamiento fue de 37,25 meses (rango:16-56). Los hallazgos indican la eficacia y la seguridad de MMF en monoterapia en nuestros pacientes con SN e hialinosis segmentaria y focal en quienes han fracasado otros tratamientos(AU)

We describe four pediatric patients with nephrotic syndrome(NS), diagnosed by biopsy of focal segmental glomerulosclerosis type 3 of them corticosteroid dependents (CD) with multiple recaídas a pesar of the treatment with corticoids and immunsupressors, and one of them was corticoid resistant (CR), in whom they started treatment with mycophenolate mofetil (MMF). Plasma levels of mycophenolic acid were monitored monthly during follow-up. Renal function (by Schwartz equation), proteinuria and other possible side effects of medication were monitored. Our patients had their first outbreaks of NS at similar ages (2 to3 years old). Two have started on mycophenolate mofetil before they had four years of age, and the other above the age of 12. Inspite of having used supra therapeutic doses median level of 5.625all the patients have kept a satisfactory clinical analytic, with ranges of renal function and normal total of proteins level, without showing a relapse (total remission) except for minor gastrointestinal side effects, without needing other associated therapies. The average duration of treatment was of 37.25 months (range between16 and 56 months). These findings suggest mycophenolate mofetil monotherapy as an efficient and safe alternative drug in the treatment of children with nephrotic syndrome and focal segmental glomerulosclerosis in which other treatments have failed(AU)

Case report: Infantile systemic hyalinosis: a dental perspective.

BACKGROUND: Infantile systemic hyalinosis is a rare genetic disorder which involves accumulation of hyaline in the skin, bones, mucous membranes, and occasionally, also in internal organs. The major manifestations include painful articular contractures, cutaneous lesions (hyperpigmentation, subcutaneous nodules), malnutrition resulting from diarrhoea, gingival, labial and buccal hypertrophy. CASE REPORT: The phenotype characteristics of infantile systemic hyalinosis (ISH) in a two year old boy were present. The characteristics of flattered occiput, limited limb movements and articular abnormalities of elbows and knees. Dental findings showed excessive gingival hypertrophy completely covering maxillary and mandibular teeth treatment. The gingival hypertrophy was surgically treated by gingivectomy under general anaesthesia. FOLLOWUP: The patient showed a full constellation of clinical manifestations of the disease. Despite the surgical intervention no improvement in oral hygiene was observed. CONCLUSIONS: Surgical treatment of the gingival hypertrophy was the treatment of choice.