Arthropathy, osteolysis, keloids, relapsing conjunctival pannus and gingival overgrowth: a variant of polyfibromatosis?

Polyfibromatosis is a rare fibrosing condition characterized by fibromatosis in different body areas and by keloid formation, and which can be associated with arthropathy and osteolysis. Familial occurrence has been described, but the cause remains unknown. Here, we describe a patient with characteristics of polyfibromatosis with arthropathy who had in addition severe conjunctival fibrosis, distinctive face, gingival overgrowth, and pigmented keloids. We discuss the resemblances and differences with polyfibromatosis and descriptions of other, similar patients. We conclude that at present it remains uncertain whether the patient has a variant of polyfibromatosis or a separate entity.

Tumoral calcinosis: a dental literature review and case report.

UNLABELLED: Tumoral calcinosis (TC) is a rare familial disease characterized by abnormal peri-articular calcification in affected joints, without any associated renal, metabolic or collagen vascular disease. It is characterized by usual hyperphosphataemia with normal serum calcium and alkaline phosphatase values. There are only a few reported cases ofTC patients with dental findings. This article reviews the dental literature and describes progressive gingival, alveolar and mandibular tori enlargement in a 41-year-old female from Zimbabwe with tumoral calcinosis. CLINICAL RELEVANCE: Tumoral calcinosis is a rare disorder of mineral metabolism with oral manifestations.

Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.

We report on two siblings doubly heterozygous for null mutations in the recently identified AGS5 gene SAMHD1. The older female child showed mild intellectual disability with microcephaly. Her brother demonstrated a significant spastic paraparesis with normal intellect and head size. Both children had an unclassified chronic inflammatory skin condition with chilblains, and recurrent mouth ulcers. One child had a chronic progressive deforming arthropathy of the small and large joints, with secondary contractures. This family illustrate the remarkable phenotypic diversity accruing from mutations in genes associated with Aicardi-Goutières syndrome (AGS). The association of arthropathy with SAMHD1 mutations highlights a phenotypic overlap of AGS with familial autoinflammatory disorders such as chronic infantile neurological cutaneous and articular syndrome (CINCA). This family therefore illustrate the need to consider mutation analysis of SAMHD1 in non-specific inflammatory phenotypes of childhood. We propose that arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutières syndrome because of SAMHD1 mutations.

[Juvenile hyaline fibromatosis]. / Fibromatose hyaline juvénile.

BACKGROUND: Juvenile hyaline fibromatosis and infantile systemic hyalinosis are two rare autosomal recessive diseases arising from mutation in the capillary morphogenesis factor-2 gene. They are characterized by accumulation of hyaline material, in the skin in the first instance and in other organs in the second. We describe a case of juvenile hyaline fibromatosis. CASE REPORT: A 2-year-old girl presented gingival hyperplasia, skin papules, subcutaneous nodules and joints and bones lesion. A diagnosis of juvenile hyaline fibromatosis was suggested and this was confirmed by histopathology and genetic analyses. The patient presented frequent episodes of diarrhoea, which is evocative of infantile systemic hyalinosis. DISCUSSION: This case clearly illustrates the wide phenotypic range of juvenile hyaline fibromatosis. Diagnosis must be made as soon as possible to avoid cosmetic and functional handicap.

Infantile systemic hyalinosis: Case report and review of the literature.

Infantile systemic hyalinosis (ISH) is a rare, progressive autosomal recessive disease, which is usually fatal by the age of 2 years. Clinical onset typically occurs within the first few weeks of life. The disease is characterized by joint contractures, osteopenia, failure to thrive, gingival hypertrophy, diarrhea, protein-losing enteropathy, and frequent infections. Dermatologic manifestations include thickened skin, hyperpigmentation, perianal nodules, and facial papules. Histopathology shows hyaline deposits in the dermis and visceral organs. We describe a patient with ISH confirmed by clinical and histopathologic findings, as well as DNA sequence analysis, which revealed a novel homozygous T118K mutation in the CMG2 gene.

Tumoral calcinosis due to GALNT3 C.516-2A >T mutation in a black African family.

Familial Tumoral Calcinosis (FTC) is a rare autosomal recessive disorder of the phosphocalcic metabolism caused by mutations in the FGF23 or GALNT3 genes. We have identified a Beninese family in which two brothers present FTC caused by a homozygous A>T transversion at the acceptor splice site in intron 1 of GALNT3 gene. We report on the clinical, biochemical, histopathological and molecular spectrum of the disorder in this family. The particularly severe phenotype, the amelogenesis imperfecta, and the carbapatite deposit observed in these patients, seem to be characteristic of our observations.

[Infantile systemic hyalinosis: a case report and literature review].

Objective: To investigate the clinical, pathological and gene mutation features of infantile systemic hyalinosis(ISH). Method: Data of a child with ISH seen in Haikou Hospital were retrospectively analyzed for the diagnosis and differential diagnosis of infantile systemic hyalinosis and the relevant reports in literature were reviewed. Result: A 1 year and 1 month old boy showed limbs joint stiffness, limited mobility and double knee flexion at his first month of life. At third month, red rashes appeared on the body and gradually became purple, most of them were seen on the back and they were higher than the skin surface, uneven and did not fade when pressed. Undergoing X-ray the boy showed double knee varus deformity. Histopathological examination of the neck skin lesions proved hyalinosis. The gene examination revealed ANTXR2 exon 13, c. 1073 delC/c.1074 delT mutations, which were hot spots mutation of ISH, then the diagnosis of ISH was confirmed. Using "Infantile systemic hyalinosis" as a keyword, literature in Wanfang network, PubMed and China National Knowledge Infrastructure from 1978 to 2015 was searched, we found 48 foreign cases, one Chinese Taiwan case. All the cases had joint contractures. Short stature and skin lesions with hyperpigmentation in 40 cases, gingival hyperplasia in 36 cases, perianal nodules in 32 cases, skin thickening in 31 cases, osteoporosis in 30 cases, recurrent diarrhea in 30 cases, repeated infections in 25 cases; 49 cases were reported as autosomal recessive genetic disease, of whom 18 cases underwent genetic testing, the pathogenic gene was located in the fourth chromosome q21 position, the gene was encoded as capillary morphogenesis Protein 2 (CMG2), also known as anthrax toxin receptor 2 (ANTXR2), but there were various mutation spots in the gene. Among the 18 cases, 9 were of frameshift, 8 of missense and 1 of splice defect . Onset ages were mainly within 4 months after birth. Without special treatment most patients died at about 2 years of age due to repeated infections. Conclusion: ISH is a rare disease, which occurs at early age. ISH has special clinical features: joint contracture and limited mobility, special skin rash and pigmentation, skin hyaline degeneration of pathological examination. ISH is an autosomal recessive genetic disease with mutation gene located in the fourth chromosome q21 position. Currently there is no effective treatment for ISH, with which patients are prone to die of recurrent infections.

Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred.

Three sisters, each with chondrocalcinosis/arthropathy, are described who have the clinical, laboratory and pathologic findings characteristic of the adult form of hypophosphatasia. Premature loss of adult teeth, arthralgias and pain from bilateral femoral pseudo-fractures were associated with subnormal circulating alkaline phosphatase levels, phosphoethanolaminuria and osteomalacia diagnosed by iliac crest biopsy. Assay of alkaline phosphatase activity in the blood of kindred members revealed hypophosphatasemia in one of two younger brothers. Several subjects in subsequent generations also had suspiciously low alkaline phosphatase activity, but did not have histories of significant dental, bone or joint disease. Review of the medical records of the sisters' parents, aunts and uncles revealed normal alkaline phosphatase levels in their father and five of his siblings, but consistently low levels in their mother and two of her siblings. Despite hypophosphatasemia, the sisters' mother and her siblings lived to old age without clinical or radiographic evidence of bone disease. Our findings suggest that although adult hypophosphatasia can be transmitted as a dominant trait in some kindreds, there is considerable variation in the clinical expression of the biochemical defect. One person, generation or family may manifest clinical bone disease and arthropathy whereas the biochemical defect may be present but remain asymptomatic in others. Furthermore, in some cases, the adult form of hypophosphatasia may represent a developmental disorder with hypophosphatasemia appearing during adulthood.

Juvenile hyaline fibromatosis: two new patients and review of the literature.

We report on a sister and a brother (born to normal consanguineous parents) with joint contractures and osteolytic lesions of bones. The sister had also gingival hyperplasia and skin lesions consisting of multiple tumors of the face, nose, palate, ears, and neck. Histologic examination showed findings of juvenile hyaline fibromatosis. The literature is reviewed, and 15 cases already reported are summarized.

New multisystemic disorder involving heart valves, skin, bones, and joints in two brothers.

We report on 2 brothers with a severe progressive disorder characterized by thick skin, acne conglobata, "coarse" face, osteolysis, gingival hypertrophy, brachydactyly, camptodactyly, and mitral valve prolapse. The youngest brother died at age 24 years because of heart failure. Biochemical and pathological studies excluded known metabolic diseases. We think that this is a new genetic disorder inherited in autosomal recessive or X-linked recessive manner.

Disease progression in Hutchinson-Gilford progeria syndrome: impact on growth and development.

OBJECTIVES: Hutchinson-Gilford progeria syndrome is a rare and uniformly fatal segmental "premature aging" disease that affects a variety of organ systems. We sought to more clearly define the bone and weight abnormalities in patients with progeria as potential outcome parameters for prospective clinical trials. PATIENTS AND METHODS: We collected and analyzed longitudinal medical information, both retrospectively and prospectively, from a total of 41 children with Hutchinson-Gilford progeria syndrome spanning 14 countries, from the Progeria Research Foundation Medical and Research Database at the Brown University Center for Gerontology. RESULTS: In addition to a number of previously well-defined phenotypic findings in children with progeria, this study identified abnormalities in the eruption of secondary incisors lingually and palatally in the mandible and maxilla, respectively. Although bony structures appeared normal in early infancy, clavicular resorption, coxa valga, avascular necrosis of the femoral head, modeling abnormalities of long bones with slender diaphyses, flared metaphyses, and overgrown epiphyses developed. Long bones showed normal cortical thickness centrally and progressive focal demineralization peripherally. The most striking finding identified in the retrospective data set of 35 children was an average weight increase of only 0.44 kg/year, beginning at approximately 24 months of age and persisting through life, with remarkable intrapatient linearity. This rate is >2 SD below normal weight gain for any corresponding age and sharply contrasts with the parabolic growth pattern for normal age- and gender-matched children. This finding was also confirmed prospectively. CONCLUSIONS: Our analysis shows evidence of a newly identified abnormal growth pattern for children with Hutchinson-Gilford progeria syndrome. The skeletal and dental findings are suggestive of a developmental dysplasia rather than a classical aging process. The presence of decreased and linear weight gain, maintained in all of the patients after the age of 2 years, provides the ideal parameter on which altered disease status can be assessed in clinical trials.

In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes.

OBJECTIVE: To establish a system for efficient, direct in vivo gene transfer into joints. METHODS: A hemagglutinating virus of Japan (HVJ; Sendai virus)-liposome suspension containing SV40 large T antigen (SVT) gene was injected intraarticularly into knee joints of 6-week-old female Lewis rats. Rats were killed at various times for immunohistochemical analysis of the expression of SVT gene. RESULTS: The expression of SVT gene was detected immunohistochemically in chondrocytes in the superficial and middle zones of articular cartilage in the knee joints. The average percentage of SVT-positive cells was estimated to be approximately 30% on days 3, 7, 14, and 21 after transfection. Moreover, no pathologic change caused by HVJ-liposome injection was observed in the joints. CONCLUSION: The transfection frequency and stability of expression recognized in this study indicate the possibility of a strategy for treatment of joint disorders, including arthritis, using direct gene transfer.

Dental lesions in tumoral calcinosis.

Tumoral calcinosis (TC) is a rare inherited autosomal dominant metabolic disease manifested by elevated serum phosphorus and 1,25 dihydroxyvitamin D levels and periarticular cystic and solid tumorous calcifications. The dental findings in a large family have been critical in determining the genetic transmission of the condition. Radiographically the teeth have short bulbous roots, pulp stones and partial obliteration of the pulp cavity. Histologically, coronal dentin and a variable amount of radicular dentin appears to be deposited regularly. At nonspecific points the developing radicular dentin appears to encounter a mass of calcified material and proceed to grow around it. This mass has a unique histologic pattern with ovoid spaces surrounded by amorphous calcification. At levels of further root development the radicular dentin has an irregular bending tubule arrangement. The dental lesion of TC appears to be different from that of radicular dentin dysplasia in histologic structure and in the method of initiation of the dentin defect. These data suggest that the specific dental lesion is a new phenotypic marker for TC.

Brachygnathia superior and degenerative joint disease: a new lethal syndrome in Angus calves.

Brachygnathia superior and generalized diarthrodial degenerative joint disease were seen in 17 related, purebred Angus calves ranging in age from 2 days to 4 months. Craniometrical studies revealed decreased maxillary and palatine bone lengths and increased cranial, skull, and facial indices. Radiological evaluation of major appendicular joints demonstrated lipping of the joint margins with osteophyte formation, sclerosis of subchondral bone, and narrowing of joint spaces. Synovial fluid evaluation indicated joint degeneration but no etiologic agent. Rheumatoid factor analysis of plasma was negative. Grossly, all major appendicular joints were defective including the atlanto-occipital articulation. Lesions ranged from loss of surface luster to erosions and deep ulcers with eburnation of the subchondral bone and secondary proliferative synovitis. Histological changes were degeneration of the articular cartilage matrix, chondrocyte necrosis, flaking and fibrillation, chondrone formation, erosions and ulcers of the articular cartilage with subchondral bone sclerosis, vascular invasion with fibrosis, and chronic, nonsuppurative, proliferative synovitis. Growth plates had defective chondrocyte proliferation and hypertrophy with aberrant ossification of calcified cartilaginous matrix. Histochemical analysis of cartilage and bone failed to incriminate which component was defective, glycosaminoglycan or collagen, but indicated different distribution or absence of one or the other. Genealogic studies revealed a genetic basis for the new defect.

Bruck syndrome: neonatal presentation and natural course in three patients.

Three unrelated patients with congenital arthrogryposis and brittle bones, the main neonatal signs of Bruck syndrome, are presented. In infancy and early childhood recurrent fractures of ribs and long bones and persistent Wormian bones in the calvarium are reminiscent of osteogenesis imperfecta (OI) even with white sclerae, normal dental quality and normal hearing as important clinical negatives. The diagnosis was made before two years of age in two, and in adolescence in the third patient. The latter's radiologically documented long-term natural course reveals slow progressivity of osteopenia and growth deficiency, worsening tendon contractures and pterygia in addition to increasing spine and pelvis deformation. Mental development remains normal. Bruck syndrome is monogenic and probably due to homozygosity of an as yet unidentified gene. As no alteration in the collagens I and III is detected and molecular screening reveals no mutation in the COL1A1 and COL1A2 genes, the pathogenesis of this severe disorder of connective tissue remains largely unknown.

Clinical features of hereditary progressive arthro-ophthalmopathy (Stickler syndrome): a survey.

PURPOSE: To define variations in the clinical manifestations of Stickler syndrome. METHODS: A questionnaire was sent to 612 persons. RESULTS: Of the 316 usable replies, 95% of persons had eye problems (retinal detachment occurred in 60% of patients, myopia in 90%, and blindness in 4%); 84% had problems with facial structures such as a flat face, small mandible, or cleft palate; 70%, hearing loss; and 90%, joint problems, primarily early joint pain from degenerative joint disease. Treatment included cryotherapy and laser therapy for retinal detachment, repair of cleft palate, use of hearing and mobility aids, and joint replacements. CONCLUSIONS: There are wide variations of symptoms and signs among affected persons, even within the same family. There are delays in diagnosis, lack of understanding among family members, denial about the risk of serious eye problems, and joint disease.