Search

A case of a 40-year-old man with dehiscence of the prosthetic aortic valve and recurrence of mycotic aneurysm of the left ventricular outflow tract with osteogenesis imperfecta is presented. He had an operation of aortic valve replacement and direct closure of the mycotic aneurysm for infective endocarditis twenty-one months ago. We performed reoperation of prosthetic aortic valve, patch closure of the mycotic aneurysm and graft replacement of the ascending aorta. He was complicated with multiple fractures of bilateral scapla and dislocation of left shoulder one postoperative day. Fortunately, cardiac reoperation was performed successfully in this patient despite anticipated difficulties with tissue friability with osteogenesis imperfecta.

We describe a girl with a severe progressive type of osteogenesis imperfecta, in association with multisutural craniosynostosis, growth failure, and craniofacial findings including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. Collagen analysis was normal. These features are consistent with the diagnosis of Cole-Carpenter syndrome. This report provides further evidence for the existence of this rare genetic entity.

Perinatal lethal osteogenesis imperfecta is the result of heterozygous mutations of the COL1A1 and COL1A2 genes that encode the alpha 1(I) and alpha 2(I) chains of type I collagen, respectively. Point mutations resulting in the substitution of Gly residues in Gly-X-Y amino acid triplets of the triple helical domain of the alpha 1(I) or alpha 2(I) chains are the most frequent mutations. They interrupt the repetitive Gly-X-Y structure that is mandatory for the formation of a stable triple helix. Most babies have their own private de novo mutation. However, the recurrence rate is about 7% owing to germline mosaicism in one parent. The mutations act in a dominant negative manner as the mutant pro alpha chains are incorporated into type I procollagen molecules that also contain normal pro alpha chains. The abnormal molecules are poorly secreted, more susceptible to degradation, and impair the formation of the extracellular matrix. The collagen fibres are abnormally organised and mineralisation is impaired. The severity of the clinical phenotype appears to be related to the type of mutation, its location in the alpha chain, the surrounding amino acid sequences, and the level of expression of the mutant allele.

Osteogenesis imperfecta (OI) is the most prevalent osteoporosis syndrome in childhood and is characterized by fractures and skeletal deformities. In almost all individuals, OI results from mutations in one of the two genes (COL1A1 and COL1A2) that encode the chains of type I collagen. OI can be divided into four major groups, type I, II, III, and IV, that differ in clinical presentation, mode of inheritance, radiographic picture, and, for the most part, the biochemical basis of the connective disorder. The molecular basis of OI is mainly discussed.

Background: Several forms of osteogenesis imperfecta have been described. The perinatally lethal forms (type II of Sillence) have been subclassified into groups A, B and C on the basis of radiological features. This report describes a case of type IIA., Case Report: A female Congolese baby was born at term to healthy, non-consanguineous parents. No ultrasonographic studies were done during the pregnancy. The newborn suffered from acute respiratory distress at birth. Clinical examination showed bone abnormalities: shortened and bowed limbs with crepitation at mobilization, soft calvaria and narrow rib cage. X-rays showed short, broad, bowed long bones with signs of fractures; the ribs were thin and beaded; wormian bones were seen in the skull. The newborn died from respiratory distress at the age of 5 hours. All clinical and X-rays investigations of the parents, the elder brother and cousins were normal., Conclusion: This baby seems to have suffered from a lethal form of osteogenesis imperfecta, probably type IIA of Sillence.

Two patients with osteoporosis pseudoglioma syndrome are described. Both are single children, born to nonconsanguineous, healthy parents. The first patient, a 17-year-old girl, had serious visual impairment since birth. She is severely dwarfed and has major skeletal deformities resulting in inability to walk since age 2 years. The second patient is an 18-year-old girl with unilateral neonatal blindness, short stature and deformities, mainly of pelvis and lower limbs. She has been able to walk with support up to now. The clinical and radiological findings in these 2 patients reflect the clinical variability of the condition. Results of collagen studies in both patients are normal and differentiate this condition clearly from severe osteogenesis imperfecta, which it resembles.

We examined collagens produced by cultured cells from skin, chorionic villi, and placental membranes of a 32 week fetus with osteogenesis imperfecta (OI) type II. We observed that skin fibroblasts synthesized two populations of pro alpha 1(I) chains of type I procollagen; one population was normal, while the other population had excessive post-translational modification. The thermal stability of helices containing the overmodified chains was reduced 1-2 degrees C. Most significantly, the cells cultured from chorionic villi produced type I collagen chains with the same electrophoretic abnormalities as the skin collagen. This suggests that chorionic villus sampling (CVS) is a means of prenatal diagnosis for families with a previous type II or type IV OI infant.

Congenital osteogenesis imperfecta (OI) was diagnosed by ultrasound in a 31-week-old fetus, and the diagnosis confirmed after delivery by caesarean section at week 36. The baby survived the neonatal period, but failed to thrive, had recurrent respiratory infections and ultimately died at 8 months. Cultured fibroblasts synthesized both normal type I collagen and unstable type I collagen harbouring a structural defect in the alpha 1 (I) cyanogen bromide-derived peptide number 8 (CB8) region of the molecule, indicating a heterozygous dominant mutation. At birth, the radiological picture was that of the "thin bone"-type of congenital OI (OI type IIB/III in the Sillence classification); at the age of 12 weeks ribs and long bones had undergone a marked expansion giving a very different picture, that of the "thick bone"-type congenital OI (OI type IIA). The mechanism responsible for this change in bone structure is not known, but fractures and callus formation are unlikely to be the only factors. Caution is needed in the interpretation of radiographs of newborns with OI for prognostic or genetic purposes.

The authors report a case of congenital fragilitas ossium diagnosed "in utero". The radiography of the fetus in the uterus showed bony abnormalities suggestive of Porak and Durante's disease. This early diagnosis is often useful because it will help to prevent trauma before and during delivery which is a principal cause of fetal death.

The authors report the results obtained in thirteen patients with osteogenesis imperfecta who were treated by the Sofield operation. This operation is indicated both in the congenital and delayed forms of the disease. The results are promising: prevention of deformities and fractures in a high percentage of cases, recovery of the ability to walk in all the patients. The incidence of complications was low, infection being the most serious. Although the use of extending rods reduces the number of reinterventions, it does not appear to improve the results and carries the risk of a greater number of complications. However, the authors have no experience of this particular technique.

The mechanism responsible for prenatal bowing of long bones was investigated based on the results of morphological observation and biochemical analysis of glycosaminoglycans of the autopsied bone from a newborn patient with classic campomelic dysplasia and the result of an experiment which produced a similar deformity in rat fetuses. An excised bone with postnatal bowing from a patient with osteogenesis imperfecta was also examined for comparison. In the case of campomelic dysplasia, marked hypertrophic change of the cambium layer of the periosteum at the concave side of the bone was noted. Parallel rays of the periosteal bone extended from the concave (posterior) side toward the apex of the bowing at the anterior side. Increased amounts and differences in composition of glycosaminoglycans were found in the diaphyseal bone on the concave side, suggesting the existence of bone with maturity retardation. In contrast, there were no such differences in the case with postnatal bowing and in the control. Congenital bowing of long bone in the patients with multiple malformations such as campomelic dysplasia is probably manifested as early as the cartilaginous model as the experimental result suggested.

This is a review of 24 patients with osteogenesis imperfecta of all age groups. 7 severe cases have been followed closely during growth for at least 10 years after multiple series of osteotomies with stabilisation by rodding and plating. The conclusion of the disappointing late results consists in that plating has to be abandoned completely during growth. The indication for rodding has to be restricted severely because of the necessity for replacement of the nails about every two year until cessation of growth. Special operative indications are outlined.

The rare condition Vrolik's syndrome and its typical radiological signs are described with reference to two cases.

Cultured skin fibroblasts from seven consecutive cases of lethal perinatal osteogenesis imperfecta (OI) expressed defects of type I collagen metabolism. The secretion of [14C]proline-labelled collagen by the OI cells was specifically reduced (51-79% of control), and collagen degradation was increased to twice that of control cells in five cases and increased by approx. 30% in the other two cases. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that four of the OI cell lines produced two forms of type I collagen consisting of both normally and slowly migrating forms of the alpha 1(I)- and alpha 2(I)-chains. In the other three OI cell lines only the 'slow' alpha (I)'- and alpha 2(I)'-chains were detected. In both groups inhibition of the post-translational modifications of proline and lysine resulted in the production of a single species of type I collagen with normal electrophoretic migration. Proline hydroxylation was normal, but the hydroxylysine contents of alpha 1(I)'- and alpha 2(I)'-chains purified by h.p.l.c. were greater than in control alpha-chains. The glucosylgalactosylhydroxylysine content was increased approx. 3-fold while the galactosylhydroxylysine content was only slightly increased in the alpha 1(I)'-chains relative to control alpha 1(I)-chains. Peptide mapping of the CNBr-cleavage peptides provided evidence that the increased post-translational modifications were distributed throughout the alpha 1(I)'- and alpha 2(I)'-chains. It is postulated that the greater modification of these chains was due to structural defects of the alpha-chains leading to delayed helix formation. The abnormal charge heterogeneity observed in the alpha 1 CB8 peptide of one patient may reflect such a structural defect in the type I collagen molecule.

Surgical treatment is a safe adjunct to the management of the child with osteogenesis imperfecta. Its objectives are to control fractures and correct deformities. It may significantly improve the functional status of the child. The long-range aim of bioscience is to determine and correct this genetic defect and thereby avoid the need for orthopedic methods of managements.

Segmentation and intramedullary rod fixation of the tibia have been found to be safe and effective procedures in osteogenesis imperfecta. An extensible rod is more difficult to insert than a solid rod due to the problem of obtaining an adequate fit distally, so the practical advantage of one type over the other is not as great as it is for the femur. When the procedure is used for the proper indications and with sufficient attention to detail, severe deformities can be corrected, thus allowing many children to become or remain ambulatory.

Although 90% of the surgical procedures performed on patients with OI are on the lower limbs, intramedullary fixation of the humerus may at times be indicated also in the upper limb for the correction of deformity and improvement of function. Upper limb deformities are generally present only in patients with severe disease (osteogenesis imperfecta congenita or osteogenesis imperfecta tarda I). The recommendations expressed in this paper are based on experience with 36 intramedullary rod fixation procedures on the upper limb in 12 patients with osteogenesis imperfecta, including 24 on the humerus, five on the radius and seven on the ulna. A Rush pin provided satisfactory fixation for the humerus, when inserted from its proximal end. Intramedullary rods were extremely difficult to insert in the forearm bones, and the author considers the operation to be rarely indicated. Two interesting and unusual problems in the upper extremities have been encountered in patients with osteogenesis imperfecta: deformity of the clavicle severe enough to cause pain and limited motion, and unicameral bone cysts in the upper humerus.

Anesthetizing a patient with osteogenesis imperfecta is an uncommon and challenging event for most anesthesiologists. The manifestations of this disease directly affect anesthetic management. The choice of anesthetic technique must be carefully considered in view of the abnormalities in such patients. Local or regional anesthesia is very useful in patients with osteogenesis imperfecta, but when general anesthesia is mandatory ketamine hydrochloride is often a good choice. Close monitoring during anesthesia and surgery is essential.

Osteogenesis imperfecta is a rare, inherited, connective-tissue disorder. The three main signs of this disease are multiple bone fractures, blue scleras, and deafness (osteosclerotic type). In our research, only a few reports of the morphologic studies of the eyes of patients with osteogenesis imperfecta were found. This report describes the ocular histopathologic condition of four cases of osteogenesis imperfecta congenita, with emphasis on the ultrastructural characteristics of the collagen in the cornea and sclera.

Ten short-limbed fetuses caused by skeletal dysplasia were diagnosed prenatally from September 1984 through July 1988. The final diagnosis was thanatophoric dwarfism in 7 cases and osteogenesis imperfecta congenita in 3 cases. The diagnosis was based on sonographic findings in all cases and postnatal radiography was performed in 3 cases for further confirmation. Sonographic examinations revealed markedly shortened limbs and other associated abnormalities, including abnormal skull appearance, pear-shaped chest with protuberant abdomen, polyhydramnios and hydrops in fetuses with thanatophoric dwarfism. Fetuses with osteogenesis imperfecta congenita were characterized by fractures of the long bones. These findings were helpful in making the specific diagnosis of short-limbed dwarfism. According to our experience, sonographic examination is effective in the prenatal diagnosis of short-limbed dwarfism.

Epiphyseal cartilage and bone tissue from two cases of osteogenesis imperfecta congenita and one control case with similar skeletal age were examined regarding their glycosaminoglycan content. The diseased bone tissue showed a 3-fold increase in glycosaminoglycans, and 20-25 per cent of the chondroitin sulphate disaccharides seemed to be disulphated. The diseased cartilages showed only traces of material with characteristics of disulphates disaccharides. No disulphates disaccharides were isolated from the control materials. No difference between diseased and control material was indicated regarding molecular size, chondroitin-4-sulphate/chondroitin-6-sulphate ratio or contents of keratan sulphate and hyaluronic acid. The disease is thus associated with fundamental changes of the glycosaminoglycan structure, and these changes may be of functional importance to the mineralization process as well as to the organisation of collagen.

Based on review of recent literature and in their own experience, authors point out basic concepts on alterations of collagen, emphasizing clinical and radiological data which differ types II and III in neonates.

The deciduous and permanent teeth in some patients with osteogenesis imperfecta syndromes are blue or brown and opalescent. As shown by radiologic examination, the pulp chambers and root canals are completely or partially obliterated by abnormal dentin. The junctions between the crowns and roots are more constricted than normal. Deciduous opalescent teeth lose their enamel readily and wear more easily than normal. Unusual wear does not occur as frequently in permanent opalescent teeth as in deciduous teeth. No relationship has been shown between the number of fractures or deformity and the degree to which the teeth are affected. In contrast, other patients with osteogenesis imperfecta have normal teeth. These clinical differences in the dentitions support the concept of genetic heterogeneity is osteogenesis imperfecta and provide information useful in genetic counseling. The differential diagnosis of opalescent teeth in osteogenesis imperfecta is not difficult provided that detailed clinical and radiologic examinations of the dentition are performed. Patients with osteogenesis imperfecta and opalescent teeth should be evaluated as soon as the deciduous teeth erupt, so that an attempt can be made to prevent loss of tooth structure. However, methods of dental care in osteogenesis imperfecta are not well delineated and deserve further study.

In osteogenesis imperfecta, time of initial fracture and radiographic appearance of long bones and ribs at time of initial fracture provide good prognostic indicators concerning survival and ambulation. Osteogenesis imperfecta congenita (OIC) comprises those patients with intrauterine and/or birth fractures. Radiographs of newborns with OIC-A show short, broad, and crumpled femurs and ribs, whereas initial radiographs of patients with OIC-B demonstrate bones with normal contours in spite of fractures. Osteogenesis imperfecta tarda (OIT) comprises those patients who fracture initially after birth. Patients with OIT-A fracture initially before walking begins, and patients with OIT-B after walking has begun. In OIC-A, 15 of 16 (94%) died; one survived but was wheelchair bound. In OIC-B, only two of 27 (8%) died, with 59% in wheelchairs and 33% ambulatory. No patients with OIT died. In OIT-A, 33% were in wheelchairs and 67% were ambulatory. In OIT-B, 100% were ambulatory.

The operation of fragmentation and intramedullary rod fixation of the femur with an extensible device has proved valuable for children with osteogenesis imperfecta because it permits these children to remain ambulatory. The use of an extensible rather than a solid rod has greatly decreased the need for reoperation.

The extensible nail for treatment of children with brittle bones offers distinct advantages over the conventional rod. It appears to elongate with growth and thus obviates periodic replacement of the rod as the child grows. Complications have been few in this and other series. Recent modifications of the technique for the femur and tibia, and various changes in the original design, constitute significant improvements in the intramedullary nail method.

Osteogenesis imperfecta (OI), a dominant genetic disorder, was examined in an exploratory case study of psychosocial implications. The cross-sectional survey sample consisted of 13 OI-affected adults and 21 families with an OI-affected child who were interviewed. Findings revealed numerous psychosocial concerns and problems in addition to their complex and lifelong medical problems. Specific problem areas differed according to the severity of the disease, type, and mode of genetic inheritance. The results indicate the need for local as well as national policy changes through legislation and extensions of existing services for low-incidence disease groups such as OI-affected persons. Implications for social work practice interventions call for greater involvement with genetic diseases, more aggressive approaches in case identification and service coordination, and performing longer-range monitoring functions than is usually the case.

Collagen from bone (femur and calvarium), rib cartilage, skin, tendon, sclera, and cornea has been isolated and purified from a deceased 4-day-old infant with osteogenesis imperfecta congenita. Amino acid analysis indicated that the content of hydroxylysine was doubled in bone collagen and increased by 55% in that of cartilage as compared with age-matched normal tissues. The levels of covalently bound glucose and galactose were proportionately increased in both collagens. Collagen purified from other tissues revealed smaller increases in lysyl hydroxylation. These data suggest that at least one form of osteogenesis imperfecta congenita is associated with a molecular alteration of collagen involving hydroxy-lysine and that this alteration is particualrly marked in collagens obtained from calcifying tissues.

Conductive, sensorineural and mixed hearing loss occur in osteogenesis imperfecta in autosomal dominant inheritance pattern. Hearing loss is generally due to the middle and inner ear pathology of osteogenesis imperfecta and only occasionally to the coincidental association of otosclerosis and osteogenesis imperfecta. Two lesions cause the conductive hearing loss of osteogenesis imperfecta: (1) functional ossicular discontinuity due either to stapes superstructure fracture or fibrous replacement, or (2) thick, crumbly, lightly fixed stapes footplate. Cochlear hair cell loss, stria vascularis atrophy and calcification, tectorial membrane distortion and perilymph hemorrhage are autopsy findings that could account for sensorineural hearing loss, which occurs in a surprisingly high percentage of osteogenesis imperfecta patients. Hearing loss occurs earlier in osteogenesis imperfecta than in otosclerosis. Distinctive acoustic impedance and X-ray abnormalities occur in osteogenesis imperfecta. Other otologic findings may include lopped pinna, notching of the helix of the pinna, rosy flush of the medial wall of the middle ear and vestibular abnormalities.

The histopathologic findings in 8 temporal bones from 5 patients with osteogenesis imperfecta congenita are reported. The otic capsule, bony walls of middle ear, and ossicles showed evidence of both deficient and abnormal ossification. Microfractures were found in the otic capsule and in the anterior process and handle of the malleus, in addition to their common location at the crura of the stapes. The cochlear and vestibular end-organs appeared normal. Pathologic changes compatible with otosclerosis were not seen. The possible implication of these changes on hearing and balance is discussed.