"Raine syndrome"

Raine syndrome: Prenatal diagnosis based on recognizable fetal facial features and characteristic intracranial calcification. The purpose of this study was to elucidate the facial morphology and the pattern of internal malformations in three fetuses with RS born to first cousins of Egyptian decent. The fetal ultrasonography findings were highly suggestive of RS leading to targeted Sanger

A novel FAM20C mutation causing hypophosphatemic osteomalacia with osteosclerosis (mild Raine syndrome) in an elderly man with spontaneous osteonecrosis of the knee. Raine syndrome is characterized by FGF23-mediated hypophosphatemic osteomalacia with osteosclerosis caused by mutations in the FAM20C gene. We report a case of a 72-year-old man who presented with rapid progressive spontaneous , respectively), as well as a low bone turnover state. Phosphate levels were low due to renal phosphate wasting and high FGF23 levels (126.5 pg/ml, reference range 23.2-95.4 pg/ml). Using gene panel sequencing, we identified a novel FAM20C heterozygous missense mutation in combination with a homozygous duplication that potentially alters splicing. Taken together, this is the first case of mild Raine syndrome

A case of Raine syndrome presenting with facial dysmorphy and review of literature. Raine syndrome (RS) - an extremely rare autosomal recessive genetic disorder, is caused by a biallelic mutation in the FAM20C gene. Some of the most common clinical features include generalized osteosclerosis with a periosteal bone formation, dysmorphic face, and thoracic hypoplasia. Many cases have also been

Raine Syndrome (OMIM #259775), Caused by FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660). In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM ) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed. Instead, in 1989 Raine and colleagues published an affected neonate considering unprecedented the striking clinical and radiographic features. In 1992, "Raine syndrome" entered MIM formally as osteosclerotic bone dysplasia, lethal (MIM #259775). In 2007, the etiology emerged as loss-of-function mutation

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations. Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. Family 1 included 3 siblings with hypoplastic Amelogenesis

Hypophosphatemic osteomalacia and bone sclerosis caused by a novel homozygous mutation of the FAM20C gene in an elderly man with a mild variant of Raine syndrome. Hypophosphatemia and increased serum fibroblast growth factor 23 (FGF23) levels have been reported in young brothers with compound heterozygous mutations for the FAM20C gene; however, rickets was not observed in these cases. We report an adult case of Raine syndrome accompanying hypophosphatemic osteomalacia with a homozygous FAM20C mutation (R408W) associated with increased periosteal bone formation in the long bones and an increase in bone mineral density in the femoral neck. The patient, a 61-year-old man, was born from a cousin-to-cousin marriage. A short stature and severe dental demineralization were reported at an elementary

Functional analysis of mutant FAM20C in Raine syndrome with FGF23-related hypophosphatemia. Raine syndrome is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Either homozygous or compound heterozygous mutations in family with sequence similarity 20, member C (FAM20C) have been reported to cause this syndrome. Recently, it was reported that fibroblast growth factor 23 (FGF23)-related hypophosphatemia was found in patients with non-lethal Raine syndrome, and Fam20c conditional knockout mice presented Fgf23-related hypophosphatemic rickets. To clarify the mechanism of how FAM20C regulates FGF23, we performed functional analysis of mutant FAM20C proteins reported in Raine syndrome. We analyzed 6 mutant

, the differential diagnosis is limited to a few diseases, with XLH (OMIM#307800) being the most frequent, accounting for approximately 80% of cases17,37. Other potential diagnoses include autosomal-dominant hypophosphataemic rickets (OMIM#193100), autosomal-recessive hypophosphataemic rickets 1 (OMIM#241520); autosomal-recessive hypophosphataemic rickets 2 (OMIM#613312); Raine syndrome (OMIM#259775), fibrous

-catenin signaling pathway and reduced level of osteoclastogenesis in the vertebrae. FAM20C plays an essential role in vertebral development; it may regulate vertebral formation through the Wnt/β-catenin signaling pathway. Mutations in the human FAM20C gene are associated with Raine syndrome. The findings of this study provide valuable clues for the clinical management of Raine syndrome regarding spine

Specific ablation of mouse Fam20C in cells expressing type I collagen leads to skeletal defects and hypophosphatemia FAM20C mutations in humans cause Raine syndrome and our previous studies showed that global inactivation of mouse Fam20C led to bone and dental defects. By crossbreeding 2.3  kb Col 1a1-Cre mice with Fam20C mice, we created 2.3  kb Col 1a1-Cre;Fam20C (cKO) mice, in which Fam20C

FAM20A binds to and regulates FAM20C localization Mutations in the Family with sequence similarity (FAM) 20 gene family are associated with mineralized tissue phenotypes in humans. Among these genes, FAM20A mutations are associated with Amelogenesis Imperfecta (AI) with gingival hyperplasia and nephrocalcinosis, while FAM20C mutations cause Raine syndrome, exhibiting bone and craniofacial/dental abnormalities. Although it has been demonstrated that Raine syndrome associated-FAM20C mutants prevented FAM20C kinase activity and secretion, overexpression of the catalytically inactive D478A FAM20C mutant was detected in both cell extracts and the media. This suggests that FAM20C secretion doesn't require its kinase activity, and that another molecule(s) may control the secretion. In this study, we found

models. Dogs are coming to the rescue as physiologically relevant large animal models. Hundreds of spontaneous genetic conditions have been described in dogs, most with close counterparts to human rare disorders. Our recent examples include the canine models of human Caffey (), van den Ende-Gupta () and Raine () syndromes. These studies demonstrate the pathophysiological similarity of human and canine

Osteosclerotic bone dysplasia in siblings with a Fam20C mutation. Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing a role in the mineralization process. Since the first case reported in 1989 by Raine et al . 21 cases have been published delineating a phenotype which associates dysmorphic features, cerebral calcifications, choanal atresia or stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All the cases described were lethal during the neonatal period except for the last two reported patients

Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia. Raine syndrome is an osteosclerotic bone dysplasia, which has proved to be lethal within the first few weeks of life in all the reported cases to date. We recently identified a chromosomal rearrangement and telomeric microdeletion in a patient with Raine syndrome and subsequently identified mutations in the FAM20C gene, located within the deleted region, in six additional Raine syndrome cases. The phenotype of Raine syndrome in the cases examined was remarkably consistent with generalized osteosclerosis of all bones, periosteal bone formation, characteristic facial phenotype and lethal within the first few weeks of life. In the current study, we have identified two unrelated individuals who presented at birth

Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine Syndrome), highlighting a crucial molecule in bone development. The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies . Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or weeks. We have identified and defined a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion in an affected subject. The extent of the deleted

dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis

* Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis

Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia

Epiphysis * Spondyloepiphyseal dysplasia congenita * Multiple epiphyseal dysplasia * Otospondylomegaepiphyseal dysplasia Osteosclerosis * Raine syndrome * Osteopoikilosis * Osteopetrosis Other/ungrouped * FLNB * Boomerang dysplasia