Case Of Osteogenesis Imperfecta Type Research Articles

Identification of Osteogenesis Imperfecta Type VI: A First Case Report from a Pakistani Family

Background: Osteogenesis imperfecta type VI (OI type VI) is a rare autosomal recessive disease of bone mineralization characterized by multiple bone fractures after six months of age, without a history of other extra-skeletal complications. SERPINF1 (serpin inhibitor clade F1) is the causative gene for this abnormality, having a chromosomal location 17p13. Many cases have been reported from different populations of the world. No case has been reported from the population of Pakistan related to this deformity. 
 Case Presentation: In the current study, we presented a case of Osteogenesis imperfecta type VI. The patient's clinical findings indicated her with short stature and progressive distortion of the skeleton, without the record of other complications like hearing problems, dental anomalies, and abnormal vision. She was 16 years old, could not walk due to deformation and weakness of lower limbs. At the time of Patient’s radiological examination, history of multiple fractures of long bones was reported. The radiological findings showed the condition of kyphoscoliotic impairment in the cervicodorsal spine. Long bones showed bowing and relatively decreased bone mineralization. Patients' sequencing data indicated a new homozygous frameshift mutation c.262_263insCCCTCTC (p. Ala91Profs*23) in SERPINF1 responsible for splice site changes in PEDF protein.
 Conclusion: This identified mutation was the first report from Pakistan, and an increase in the pathogenic variants in SERPINF1 caused OI type VI.

Osteogênese Imperfeita em cão jovem da raça pinscher

Background: Osteogenesis imperfecta is a severe genetic disease rarely described in veterinary medicine. This multisystemic condition is caused by a defect in the production and metabolization of collagen, which implicates in bone fragility. This disease has been described in cattle, sheep, domestic felines, mouse and dogs of different breeds, including collie, golden retriever, beagle, dachshund and chow chow. Animals affected by this condition present multiple fractures without previous occurrence of trauma. Therefore, this report aimed to describe a case of osteogenesis imperfecta type III in a miniature pinscher dog.Case: A 1-year-old male miniature pinscher dog, was admitted for clinical evaluation in Fortaleza, Brazil, with a history of spontaneous fractures without known causes. This animal was maintained indoors, fed on dry feed and presented recurrent events of claudication and pain. In the physical examination, the individual walked solely with the forelimbs, avoiding the use of the hind limbs and presented pain behavior. Bulging of the skull was observed laterally, which promoted a triangular appearance of head and face. Fontanelles were soft, and the eyes presented blueish sclera and corneal opacity. Teeth were small, translucid, fragile and deformed. Radiography images revealed bulging of the calvaria and persistent fontanelles with open cranial sutures. In addition, cranial convolutions were less clear, which was compatible with hydrocephalus. Dental roots were narrow, short and presented partial pulp obliteration. The radiographic contrast of the dentin was low with a reduction of periapical radiolucency. Bone radiopacity was low in the bones of the abdomen and pelvis, in addition to femur. Metaphysis of the right tibia was enlarged and angular. Multiple fractures were identified in the pelvis with the formation of opaque bony calluses and bone marrow sclerosis. Physiological parameters and blood test results were unaltered. After the diagnosis of osteogenesis imperfecta type III, treatment was performed with meloxicam 0.1 mg/kg, SID, VO) and tramadol (2 mg/kg, TID, VO) until pain was controlled. When the patient was stable, the treatment was halted until the next event of fractures followed by pain.Discussion: Type I collagen is considered the most abundant protein in connective tissue, accounting for 95% of the various types of collagen found in bone tissue. In osteogenesis imperfecta, there is a shortage in coding of type I collagen, which prevents this protein from exerting its structural functions properly. In addition, it is subjected to intra and extracellular degradation, affecting cell migration and differentiation and, concomitantly, cell-matrix interaction. Hence, these changes are considered the main pathophysiological factors of osteogenesis imperfecta. There is a wide range of phenotypic presentations in individuals with osteogenesis imperfecta. However, there is a pattern of fractures and features that aid clinically and radiologically in the characterization of the disease and form the basis for case identification and diagnosis. In this case, the diagnosis was concluded primarily considering significant clinical signs, such as: repetitive fractures, triangular face, bulging of the skull, bluish sclera and corneal opacity. Radiographic examinations were used to confirm the diagnosis and to aid in treating the fractures. Although the genetic test provides a better understanding of the disease, it was not performed in this case, as it is routinely unavailable in many treatment centers. In conclusion, we described a case of osteogenesis imperfecta in a miniature pinscher dog.

A case of osteogenesis imperfecta type II, a diagnosis made almost too late in a resource poor setting

Background: Osteogenesis imperfecta (OI) is a rare autosomal dominant disorder of type I collagen (COL I), characterised by excessive bone fragility with low bone mineral density (BMD). Type II is associated with extreme bone fragility leading to intrauterine or early infant death.Objective: To highlight a case of OI type II and the need for an early detection of this rare bone disorder through non invasive prenatal diagnosis.Case Report: We report a case of a full term male neonate with progressive respiratory distress from birth. He was seen in children’s emergency room two hours after vaginal delivery in a peripheral clinic. Pregnancy and delivery were uneventful and the baby was born to non-consanguineous, monogamous parents. On examination he was dyspnoeic, cyanosed with malformed and fractured upper and lower limbs. A working diagnosis of osteogenesis imperfecta type II was made and baby was placed on oxygen via face mask. However respiratory distress worsened and baby died at 6 days of life.Conclusion: Antenatal ultrasonography might have led to diagnosis in utero. If detected prenatally a more appropriate management can be instituted to reduce morbidity and mortality.

English

Introduction Osteogenesis imperfecta type II is one of the more common lethal skeletal dysplasias with prenatal onset. The prenatal ultrasound scan may suggest the presence of severe short limb skeletal dysplasias and can accurately predict lethality, but the final diagnosis, typing and subtyping of the specific genetic skeletal disorder are mainly based on the postmortem radiography. Histopathology of the bone and car- tilage can be contributory in vari- ous skeletal dysplasias, and, in the case of osteogenesis imperfecta can be diagnostic. We describe a case of osteogenesis imperfecta type II diagnosed in a 14-week gestation foetus on the basis of the typical histopathological findings on curet- tage material. This report highlights the utility of histological diagnosis in certain skeletal dysplasias, even in the absence of reliable postmor- tem radiographic control, as is the case with curettage material in early termination of pregnancy. In addi- tion, we document the presence of limb and rib fractures as early as the 14th week of gestation, and confirm that osteogenesis imperfecta type II can present in the first-trimester ultrasound scan with increased nuchal translucency, ventriculo- megaly and generalised oedema,

A Case of Osteogenesis Imperfecta Type II Caused by a Novel COL1A2 Gene Mutation: Endoscopic Third Ventriculostomy to Prevent Hydrocephalus

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder caused by defects in type I collagen synthesis. OI is generally classified into four types (I to IV), and the clinical prognosis varies from a lethal outcome for type II and varying deformities for type III to a normal lifespan for the other types. We describe a female patient with biochemically confirmed OI caused by a novel mutation in the COL1A2 gene. Persistence of blue sclerae supported the diagnosis of OI type II. The case was complicated with obstructive hydrocephalus, for which endoscopic third ventriculostomy (ETV) was performed. The ETV was transiently effective for the obstructive hydrocephalus. The patient subsequently developed brain atrophy, partly through ischemic events after the ETV, which appeared to contribute to maintenance of smooth circulation of the cerebrospinal fluid. We conclude that continuous and adequate medical care including ETV can facilitate long-term survival even in lethal OI type II.

Osteogenesis imperfecta type VIII: A case report

Osteogenesis imperfecta is a genetic bone disorder that requires a multi-disciplinary healthcare team to achieve optimal patient outcomes. It is most recognized by excessive brittleness of the bones, and has several classification types, with varying levels of severity. In 2007, type VIII was added to the classification system as a severely deforming and lethal autosomal recessive gene associated with mutations of CRTAP and LEPRE1 genes. The purpose of this case report is to describe a rare case of osteogenesis imperfecta type VIII in the neonate and the multi-disciplinary approach required to manage the patient's care; that includes a variety of nursing specialties.

Orthognathic surgery in osteogenesis imperfecta: a case report with management considerations

Osteogenesis imperfecta is a disease of connective tissues with additional metabolic defects. It is associated with recognisable facial disproportion and sometimes warrants surgical intervention for aesthetic, functional and psychological reasons. A severe case of osteogenesis imperfecta type 3 is presented to illustrate the feasibility of bimaxillary surgery using a mandibular body step osteotomy and maxillary down grafting at the Le Fort I level. The medical, anaesthetic, surgical and specific maxillofacial implications of surgery in these patients are discussed.

Skeletal Dysplasia in Perinatal Lethal Osteogenesis Imperfecta A Complex Disorder of Endochondral and Intramembranous Ossification

Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis.

Characterization of a type I collagen α 2(I) glycine-586 to valine substitution in osteogenesis imperfecta type IV. Detection of the mutation and prenatal diagnosis by a chemical cleavage method

A chemical cleavage method for detecting mismatched bases in heteroduplexes formed between patient mRNA and control cDNA probes was employed to identify a single base mutation in a heterozygous case of osteogenesis imperfecta type IV. The parents' fibroblast mRNA did not contain the mutation. The region of the mRNA mismatch was amplified by using the polymerase chain reaction, cloned and sequenced. A point mutation of G to U at base-pair 2162 of the collagen alpha 2(I) mRNA resulted in the substitution of glycine by valine at amino acid position 586 of the helix. This substitution disrupted the critical Gly-Xaa-Yaa repeating unit of the collagen triple helix and resulted in helix destabilization, as evidenced by a decreased thermal stability. This local disturbance to helix propagation from the C-terminus to the N-terminus led to the overmodification of the collagen helix downstream towards the N-terminus. However, collagen secretion in vitro was normal, and the clinical phenotype probably resulted from the secretion into the extracellular matrix of the mutant collagen combined with a decrease in collagen production to 65% of control values. The rapid detection of the osteogenesis imperfecta mutation by using the chemical cleavage method afforded the opportunity to apply the technique to prenatal diagnosis in the next pregnancy of the mother of the osteogenesis imperfecta patient. The absence of a mismatched base in chorionic villus mRNA and control cDNA heteroduplexes indicated that the foetus did not carry the mutation, which was confirmed by the subsequent delivery of a normal baby.

Genetic amniocentesis: 505 cases performed before the sixteenth week of gestation

Between May 1987 and November 1988, 505 early amniocentesis within the 15th week of gestation were performed at the First Department of Obstetrics and Gynaecology, 'L. Mangiagalli' of the University of Milan and at the Department of Obstetrics and Gynaecology of 'Gaslini' hospital in Genoa. A total number of ten abnormal fetal karyotypes were diagnosed. In addition, one case of pseudomosaicism (not confirmed on fetal blood) and one case of osteogenesis imperfecta type II (observed at ultrasound examination) were also detected. Eleven pregnancies were therefore terminated because of an abnormal fetus. Out of 494 pregnancies (excluding terminated pregnancies) there were 16 fetal losses within the 28th week; ten of these occurred in the 2 weeks following the procedure. There were 475 live-births, of which 447 were term deliveries and the other 28 deliveries occurred before the 37th week of gestation.