71 Osteogenesis Imperfecta, Type I
Osteogenesis Imperfecta, Type I 791
OI with blue sclerae, osteogenesis imperfecta tarda, Van der Hoeve syndrome
Bone fragility, blue sclerae
Incidence of all types of osteogenesis imperfecta: 0.5 in 10,000 births.
Genetics
Autosomal dominant (OMIM 166200), due to muta- tions of COL1A1 gene on 17q21.31-q22 or of COL1A2 gene on 7q22.1, lack of expression of one of the gene alleles (‘functional null’ alleles) resulting in 50% re- duction in synthesis of normal procollagen I (secre- tion, posttranslational modification, and molecular assembly of procollagen are normal); parental mo- saicism possible; paternal age effect (smaller than in other dominant disorders).
Clinical Features
(Marked Variability of Clinical Expression)
• Mild short stature or normal stature
• Blue sclerae, arcus cornea in 3rd decade
• Dentinogenesis imperfecta (60%), opalescent teeth, increased susceptibility to caries, malocclu- sion
• Hearing loss (50%), usually beginning as a con- ductive deficit in the 2nd–3rd decade and showing progressively more sensorineural component with age
• Thin skin, increased width of scars, hernias, exces- sive sweating
• Aortic root dilatation (10–25%), mitral valve pro- lapse (10%)
• Multiple skeletal fractures with minimal trauma (10% at birth, higher frequency in infancy and childhood), normal bone remodeling
• Hyperextensible joints (particularly the distal in- terphalangeal joints of hands and feet), in occa- sional cases joint dislocation (radial head)
• Easy bruising, increased bleeding tendency
Differential Diagnosis
• Other types of OI, especially OI types IV and V (normal sclerae, short stature, bowing of long bones, less frequent fractures; additionally in type V, hyperplastic callus formation and calcification of the interosseous membrane between radius and ulna)
• Child abuse syndrome
• Bruck syndrome (osteopenia + multiple fractures + wormian bones + progressive joint contrac- tures)
• Other osteoporotic disorders (idiopathic osteo- porosis, geroderma osteodysplasticum, osteo- porosis-pseudoglioma syndrome, Hajdu-Cheney syndrome, secondary osteoporosis)
Radiographic Features Generalized Bone Defects
• Osteoporosis, thin cortices, poorly trabeculated spongiosa
• Multiple fractures, normal healing of fractures Skull
• Retarded mineralization of the calvarium, wormi- an bones (70%), platybasia
• Hypoplastic dentin, short and thin dental roots, late eruption of teeth, multiple caries (group B)
• Varying degrees of calvarial thickening in adults Spine
• Occipitalization of atlas, basilar impression
• Kyphoscoliosis
• Biconcave flattened vertebral bodies Extremities
• Thin shafts of long bones
• Bowing deformities of long bones (not mandato- ry, often improve with age)
Chest
• Thin, undermineralized ribs
• Pectus excavatum/carinatum O
Bibliography
Andersen PE, Hauge M. Osteogenesis imperfecta: a genetic, radiological, and epidemiological study. Clin Genet 1989;
36: 250–5
Bauze RJ, Smith R, Francis MJO. A new look at osteogenesis imperfecta: a clinical, radiological and biochemical study of forty-two patients. J Bone Joint Surg Br 1975; 57: 2–12 Beighton P. Familial dentinogenesis imperfecta, blue sclerae,
and wormian bones without fractures: another type of osteogenesis imperfecta? J Med Genet 1981; 18: 124–8 Byers PH. Osteogenesis imperfecta. In: Royce PM, Steinmann B
(eds.) Connective tissue and its heritable disorders: molec- ular, genetic, and medical aspects. Wiley-Liss, New York, 1993, pp. 317–50
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Garretsen TJ, Cremers CW. Clinical and genetic aspects in autosomal dominant inherited osteogenesis imperfecta type I. Ann NY Acad Sci 1991; 630: 240–8
Levin LS, Young RJ, Pyeritz RE. Osteogenesis imperfecta type I with unusual dental abnormalities. Am J Med Genet 1988;
31: 921–32
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Sillence DO. Osteogenesis imperfecta nosology and genetics.
Ann NY Acad Sci 1988; 543: 1–15
Steinmann B, Superti-Furga A, Giedion A. Osteogenesis imper- fecta. In: Dihlmann W, Frommohold W (eds.) Radiologis- che Diagnostik in Klinik und Praxis. Thieme, Stuttgart, 1991, pp. 728–45
Vetter U, Pontz B, Zauner E, Brenner RE, Spranger J. Osteogen- esis imperfecta: a clinical study of the first ten years of life.
Calcif Tissue Int 1992; 50: 36–41 Osteogenesis Imperfecta, Type I
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Fig. 71.1. Patient 1, newborn. Frontal bossing, relative macro- cephaly, tibial bowing due to spontaneous fractures at birth.
(Reprinted, with permission, from Mastroiacovo et al. 1990)
Fig. 71.2.
Patient 2, age 4 years. Only mild undermineralization of the spine is apparent, in the absence of vertebral col- lapse
Osteogenesis Imperfecta, Type I 793
O
Fig. 71.3. aPatient 2, age 4 years. Note rarefied, thin, slightly bowed tubular bones. b, c Patient 3, age 9 years. Note marked osteo- porosis and healing fractures of distal femoral (arrowhead) and tibial shafts (arrow)
a b c
