Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation.
Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI).
Obafemi
Abimbola A
AA
Bone and Extracellular Matrix Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA.
Bulas
Dorothy I
DI
Troendle
James
J
Marini
Joan C
JC
D000293:Adolescent; D000328:Adult; D002114:Calcinosis / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000145:classification / Q000000981:diagnostic imaging* / Q000235:genetics; D011859:Radiography; D012189:Retrospective Studies; D013977:Tibia / Q000000981:diagnostic imaging
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D003094:Collagen
J Med Genet. 1979 Apr;16(2):101-16
458828
Cell Cycle. 2007 Jul 15;6(14):1675-81
17630507
Chir Narzadow Ruchu Ortop Pol. 2005;70(3):185-7
16294692
Calcif Tissue Int. 1992 Jan;50(1):36-41
1739868
Am J Med Genet. 1986 Mar;23(3):821-32
3953678
Annu Rev Biochem. 1995;64:403-34
7574488
Cell. 2006 Oct 20;127(2):291-304
17055431
Hum Mutat. 2007 Mar;28(3):209-21
17078022
Nat Genet. 2007 Mar;39(3):359-65
17277775
J Bone Miner Res. 2003 Feb;18(2):237-43
12568401
Bone. 2002 Jul;31(1):12-8
12110406
Radiology. 1980 Aug;136(2):351-8
7403509
J Bone Miner Res. 2005 Jun;20(6):977-86
15883638
Clin Orthop Relat Res. 1981 Sep;(159):42-57
7285469
Monatsschr Kinderheilkd. 1993 Dec;141(12):940-5
8114777
N Engl J Med. 2006 Dec 28;355(26):2757-64
17192541
Hum Mutat. 2008 Dec;29(12):1435-42
18566967