Raine syndrome: report of a family with three affected sibs and further delineation of the syndrome

Hülskamp, Georg; Wieczorek, Dagmar; Rieder, Harald; Louwen, Frank; Hörnig-Franz, I; Rickert, Christian H.; Horst, Jürgen; Harms, Erik; Rehder, Helga

doi:10.1097/01.mcd.0000080413.95344.60

Cited by 29 publications

(22 citation statements)

References 14 publications

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“…Another hitherto unreported feature is cerebellar hypoplasia and pachygyria that we observed. We reviewed the literature and tabulated the features of Raine syndrome based on 15 papers (Table I) [Raine et al, 1989;Al Mane et al, 1996;Rejjal et al, 1998;Shalev et al, 1999;Acosta et al, 2000;Rickert et al, 2002;Hulskamp et al, 2003;Al-Gazali et al, 2003;Gunes et al, 2005;Chitayat et al, 2007;Kochar et al, 2010Gaigi et al, 2011Koob et al, 2011;Fardin et a, 2011;Ababneh et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Report of a case of Raine syndrome and literature review

Seidahmed

Alazami

Abdelbasit

et al. 2015

American J of Med Genetics Pt A

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We report on a case of Raine syndrome with a mutation in FAM20C and typical phenotypic features consisting of midface hypoplasia, hypoplastic nose, choanal atresia, wide fontanelle, exophthalmos, generalized osteosclerosis and intracranial calcification. New features in our patient are cerebellar hypoplasia and pachygyria. We review the literature and conclude that the triad of hypoplastic nose, exophthalmos and generalized osteosclerosis and/or intracranial calcification is consistent in all molecularly confirmed cases.

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Section: Discussionmentioning

confidence: 99%

Report of a case of Raine syndrome and literature review

Seidahmed

Alazami

Abdelbasit

et al. 2015

American J of Med Genetics Pt A

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“…The first reported case of Raine syndrome was presented in 1989; a female neonate, born at term, who died at the age of 86 min (2). Since this original description an additional 16 cases have been described (3–12). Radiographic studies have shown generalized increase in the density of all bones and marked increase in the ossification of the skull (13).…”

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confidence: 99%

“…Periosteal bone formation is also characteristic of this disorder and differentiates it from osteopetrosis and other known lethal and non‐lethal osteosclerotic bone dysplasias (10). The periosteal bone formation typically extends along the diaphysis of long bones adjacent to areas of cellular soft tissue (12).…”

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confidence: 99%

Mutations in FAM20C also identified in non‐lethal osteosclerotic bone dysplasia

et al. 2009

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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 with a sclerosing bone dysplasia with features very similar to those in Raine syndrome but who survived infancy and are now aged 8 and 11 years, respectively. Mutations in FAM20C, consistent with autosomal recessive inheritance, were identified in both cases. In the first case, a homozygous non-synonymous mutation in exon 7 (1309G>A D437N) was identified, and in the second case, compound heterozygosity for non-synonymous mutations in exon 2 (731T>A I244N) and in exon 3 (796G>A G266R) was revealed. Raine syndrome has been previously considered to be a neonatal lethal condition. However, the identification of mutations in these two patients confirms a broader phenotypic spectrum and that mutation of FAM20C does not always lead to the infantile lethality previously seen as a prerequisite for Raine syndrome diagnosis.

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“…59 The periosteal bone formation typically extends along the diaphysis of long bones. 44 Affected individuals usually die at birth from respiratory failure, with autopsy findings of generalized osteosclerosis. 86 However, recent findings have shown a much wider clinical spectrum associated with FAM20C mutations in humans than the classic neonatal lethal presentation.…”

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Amelogenesis Imperfecta and Other Biomineralization Defects in Fam20a and Fam20c Null Mice

et al. 2012

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The FAM20 family of secreted proteins consists of three members (FAM20A, FAM20B, and FAM20C) recently linked to developmental disorders suggesting roles for FAM20 proteins in modulating biomineralization processes. The authors report here findings in knockout mice having null mutations affecting each of the three FAM20 proteins. Both Fam20a and Fam20c null mice survived to adulthood and showed biomineralization defects. Fam20b -/-embryos showed severe stunting and increased mortality at E13.5, although early lethality precluded detailed investigations. Physiologic calcification or biomineralization of extracellular matrices is a normal process in the development and functioning of various tissues (eg, bones and teeth). The lesions that developed in teeth, bones, or blood vessels after functional deletion of either Fam20a or Fam20c support a significant role for their encoded proteins in modulating biomineralization processes. Severe amelogenesis imperfecta (AI) was present in both Fam20a and Fam20c null mice. In addition, Fam20a-/-mice developed disseminated calcifications of muscular arteries and intrapulmonary calcifications, similar to those of fetuin-A deficient mice, although they were normocalcemic and normophosphatemic, with normal dentin and bone. Fam20a gene expression was detected in ameloblasts, odontoblasts, and the parathyroid gland, with local and systemic effects suggesting both local and/or systemic effects for FAM20A. In contrast, Fam20c-/-mice lacked ectopic calcifications but were severely hypophosphatemic and developed notable lesions in both dentin and bone to accompany the AI. The bone and dentin lesions, plus the marked hypophosphatemia and elevated serum alkaline phosphatase and FGF23 levels, are indicative of autosomal recessive hypophosphatemic rickets/osteomalacia in Fam20c -/-mice.Keywords amelogenesis imperfecta, knockout, rickets, phosphatonin, ectopic mineralization, biomineralization, dentin, osteomalacia, osteosclerosisThe FAM20 family of secreted proteins in mammals consists of three members (FAM20A, FAM20B, and FAM20C) that were initially thought to have roles in regulating the differentiation and function of hematopoietic and other tissues. 65 Since then, there have been reports linking mutations in both FAM20A and FAM20C to developmental disorders involving bones and/or teeth, suggesting a role for FAM20 proteins in modulating biomineralization processes. In humans, a mutation in FAM20A was recently linked to the occurrence of amelogenesis imperfecta and gingival hyperplasia in a consanguineous family. 69 However, lesions were not reported in bones or teeth of transgenic mice with a partial deletion of Fam20a, and their stunted growth was attributed to malnutrition and an unspecified metabolic disorder. 4 To the best of our knowledge, there have been only two reports elucidating the function FAM20B, which was shown to be a kinase that phosphorylates glycosaminoglycans 50 and in vivo to be involved in cartilage matrix production and skeletal development in zebrafish. 2...

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Raine syndrome: report of a family with three affected sibs and further delineation of the syndrome

Cited by 29 publications

References 14 publications

Report of a case of Raine syndrome and literature review

Report of a case of Raine syndrome and literature review

Mutations in FAM20C also identified in non‐lethal osteosclerotic bone dysplasia

Amelogenesis Imperfecta and Other Biomineralization Defects in Fam20a and Fam20c Null Mice

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