Prenatal Diagnosis Of Osteogenesis Imperfecta Research Articles

Assessment of the health status and pharmacological treatment of neonates with osteogenesis imperfecta – 20-year single-centre observations

Introduction and objective: Osteogenesis imperfecta is a heritable bone dysplasia resulting in reduced bone mineral density. Fractures of long bones, which are the dominant symptom of osteogenesis imperfecta, can be diagnosed already in foetal life. Multiple fractures are associated with severe pain, which may cause deterioration of the newborn’s general condition, respiratory and circulatory disorders, and reduced general motor activity. The aim of the study was to summarise the experience resulting from many years of care and treatment of neonates with osteogenesis imperfecta types II and III. Materials and methods: The study included 53 newborns with osteogenesis imperfecta hospitalised at the Department of Paediatrics, Newborn Pathology and Bone Metabolic Diseases in the years 2001–2021. All children underwent a babygram and an assessment of their health status, including calcium and phosphorus metabolism parameters. Results: In 67.3% of cases, the mother was informed before delivery that she would give birth to a sick child. The general condition of the newborns was moderately severe to severe in 43.4%. Physical examination revealed abnormal body proportions related to previous fractures in 98.1% of patients, including long bones of limbs. More than 10 fresh bone fractures were diagnosed in 34% of children. Conclusions: Prenatal diagnosis of osteogenesis imperfecta indicates its severe course (multiple fractures) in the neonatal period. Therefore, it requires care in a specialised centre that will provide safe, symptomatic pharmacological treatment (bisphosphonates) to reduce both pain and the risk of further bone fractures.

Case Report: A prenatal diagnosis of osteogenesis imperfecta in a patient with a novel pathogenic variant in COL1A2

Osteogenesis imperfecta is considered a rare genetic condition which is characterized by bone fragility. In 85% of cases, it is caused by mutations in COL1A1 and COL1A2 genes which are essential to produce type I collagen. We report the case of a female neonate delivered to a 27-year-old women at San Bartolomé Teaching Hospital with a family history of clavicle fracture. A prenatal control with ultrasound was performed to the mother at 29 weeks. A fetus with altered morphology and multiple fractures was found. Therefore, a prenatal diagnosis of osteogenesis imperfecta was performed. The neonate was born with a respiratory distress syndrome and an acyanotic congenital heart disease. Therefore, she remained in NICU until her death. We highlight the importance of prenatal diagnosis, genetic counseling and a multidisciplinary evaluation in this type of pathologies and report a new probably pathogenic variant in the COL1A2 gene detected by exomic sequencing in amniotic fluid.

Case Report: A prenatal diagnosis of osteogenesis imperfecta in a patient with a novel pathogenic variant in COL1A2

Osteogenesis imperfecta is considered a rare genetic condition which is characterized by bone fragility. In 85% of cases, it is caused by mutations in COL1A1 and COL1A2 genes which are essential to produce type I collagen. We report the case of a female neonate delivered to a 27-year-old women at San Bartolomé Teaching Hospital with a family history of clavicle fracture. A prenatal control with ultrasound was performed to the mother at 29 weeks. A fetus with altered morphology and multiple fractures was found. Therefore, a prenatal diagnosis of osteogenesis imperfecta was performed. The neonate was born with a respiratory distress syndrome and an acyanotic congenital heart disease. Therefore, she remained in NICU until her death. We highlight the importance of prenatal diagnosis, genetic counseling and a multidisciplinary evaluation in this type of pathologies and report a new probably pathogenic variant in the COL1A2 gene detected by exomic sequencing in amniotic fluid.

Analysis of COL1A1 gene variants in five Chinese pedigrees affected with osteogenesis imperfecta

To detect potential variants of COL1A1 gene in five Chinese pedigrees affected with osteogenesis imperfecta (OI) and provide prenatal diagnosis for a fetus at 11th gestational week. The coding regions and exon/intron boundaries of 225 genes associated with bone diseases were subjected to targeted capture and next generation sequencing (NGS). Suspected mutations were verified with Sanger sequencing in the probands, unaffected relatives and 100 unrelated healthy controls. Prenatal diagnosis for a high-risk fetus was carried out by Sanger sequencing. The probands of the pedigrees 1-5 have respectively carried c.3226G>A (p.Gly1076Ser), c.579delT (p.Gly194Valfs*71), c.2911-2912insAG (p.Gly971Glufs*138), c.3037G>A (p.Gly1013Arg) and c.642+5G>A variants of the COL1A1 gene. For pedigree 1, the same variant was not found in the fetus. c.3037G>A (p.Gly1013Arg) and c.2911-2912insAG (p.Gly971Glufs*138) were not reported previously. Mutations of the COL1A1 gene probably underlie the OI in the five pedigrees. Combined NGS and Sanger sequencing can provide an effective and accurate method for the genetic and prenatal diagnosis of OI.

Three-dimensional ultrasound in the prenatal diagnosis of osteogenesis imperfecta

ObjectiveFetal osteogenesis imperfecta (OI) is a heterogeneous group of collagen disorders characterized by bone fragility, blue sclerae, deafness, and dentinogenesis imperfecta. Ultrasonography is acknowledged as a reliable diagnostic modality for the prenatal diagnosis of OI, especially type II. In the past, two-dimensional (2D) ultrasound (US) has been applied as the mainstay of prenatal diagnosis of OI. In this series, we report our work of detecting OI using three-dimensional (3D) US. Material and MethodsWe reviewed our computer database of prenatal diagnosis of OI at the National Cheng Kung University Hospital from April 1996 to July 2010. All the cases were scanned by 2D and 3D US. In total, six cases of fetal OI were diagnosed. ResultsCompared with 2D US, 3D US can detect fetal OI precisely, and provide additional vivid illustration after various modes of reconstruction that 2D US cannot. ConclusionIn conclusion, 3D US may contribute significantly to the detection of OI in utero and provide a novel visual depiction of this defect after reconstruction. The technique may thus substantially assist in prenatal diagnosis as well as consultations for fetal OI.

Prenatal Diagnosis and Management of Intrauterine Fracture

Intrauterine fracture is an extremely rare finding, but can occur as the result of maternal trauma, osteogenesis imperfecta (OI), or theoretically other metabolic/structural abnormalities. Increased clinical awareness of the diagnosis and optimal management of these cases can lead to more positive outcomes for the patient and her child. Blunt abdominal trauma late in gestation increases the risk of fetal skull fracture, while a known diagnosis of OI or other abnormalities leading to decreased fetal bone density creates concern for long bone fracture. Biochemical and genetic tests can aid in the prenatal diagnosis of OI, while ultrasound is the best overall imaging modality for identifying fetal fracture of any etiology. When fetal fracture is diagnosed radiologically, specific management is recommended to promote optimal outcomes for mother and fetus, with special consideration given to the mother with OI. With the exception of fetal fractures due to lethal conditions, cesarean delivery is recommended in most cases, especially when fetal or maternal well-being cannot be assured. When a patient presents with risk factors for intrauterine fracture, careful evaluation via thorough history-taking, ultrasonography of the entire fetal skeleton, and laboratory tests should be performed. Heightened awareness of intrauterine fracture allows better postpartum management, whether for simple fracture care or for long-term care of patients with OI or genetic/metabolic abnormalities. Obstetricians & Gynecologist, Family Physicians. After completion of this educational activity, the reader will be able to compare x-ray, ultrasound modalities and MRI and their utility in diagnosing fetal fracture. Formulate a differential diagnosis for fetal fracture. Propose a delivery plan for a patient whose fetus has a prenatally diagnosed fetal fracture.

Supporting Pregnant Women through Difficult Decisions: A Case of Prenatal Diagnosis of Osteogenesis Imperfecta

Supporting Pregnant Women through Difficult Decisions: A Case of Prenatal Diagnosis of Osteogenesis Imperfecta

P11.20: Prenatal diagnosis of osteogenesis imperfecta by mean of three‐dimensional ultrasound

P11.20: Prenatal diagnosis of osteogenesis imperfecta by mean of three‐dimensional ultrasound

Prenatal diagnosis of Osteogenesis imperfecta type II

Objective: To characterize the prenatal sonographic features of Osteogenesis imperfecta (OI) type II. Design: Descriptive (case series). Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University. Subjects: Six fetuses with prenatal diagnosis of OI were evaluated. Results: Six fetuses were prenatally diagnosed as OI type II in five mothers without familial history of the disease. One mother had two consecutive pregnancies complicated with this condition. The first five cases were classified as OI type IIA, while the last one was OI type IIB. All of subtype A exhibited typical triad of bone shortening, diffuse hypomineralization and multiple fractures of long bones including beaded ribs whereas the subtype B showed shortening of only femurs, normal bone echodensity and isolated fractures of long bones. The postnatal radiography and autopsy confirmed the prenatal diagnosis in all cases. Other findings may occasionally be found, including polyhydramnios, oligohydramnios, hydrop fetalis and small for gestational age. Conclusion: The triad of bone shortening, decreased bone density and numerous fractures including beaded ribs permits a confident diagnosis of OI type IIA. Furthermore, sonographic features may differentiate the subtype of OI type II, depending on degree of bone shortening and echodensity.

Non-invasive prenatal diagnosis of osteogenesis imperfecta.

The main mode of non-invasive prenatal diagnosis of osteogenesis imperfecta (OI) is fetal imaging, either by radiography or detailed ultrasonography. Radiography is more of historical interest and ultrasonography is in practice virtually exclusively used for non-invasive second trimester diagnosis of OI. Both methods have also been reported later in pregnancy when diagnosis allows the most appropriate method of delivery to be planned. For example, a caesarean section can be avoided if the fetus is shown to have a form of OI associated with limited survival. Ultrasonography is useful mainly for prenatal diagnosis of the severe forms of OI, especially the perinatally lethal forms (Sillence type II) and to a lesser extent for the severe progressively deforming forms (Sillence types III and III/IV). For the milder varieties of OI (Sillence types I and IV), many cases will be missed by scans. Invasive methods of prenatal diagnosis of OI (principally chorion villous sampling) are used for families with the milder dominant forms of OI and in severe forms of OI in which the actual biochemical or molecular defect in type I collagen is known. Many cases of type II OI and a few of type III have now been reported which were detected by scans before 20 weeks gestation, the earliest being at 15 weeks, for type IIA OI. These include cases not only at genetic risk but also sporadic cases in which scans were done either routinely or for obstetric indications. The ultrasonic abnormalities which are found include reduced echogenicity, multiple fractures, and deformity of the long bones, ribs and skull.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal diagnosis of osteogenesis imperfecta by identification of the concordant collagen 1 allele.

Dominantly inherited osteogenesis imperfecta is consistently linked to the two loci encoding the alpha 1 and alpha 2 subunits of collagen 1, the predominant bone collagen. We have performed several prenatal diagnoses based on identification of the segregating allele at the concordant locus in chorionic villus samples both in families where the linkage can be independently shown and in those where it cannot. Especially in the latter category, calculation of the final risk must incorporate an estimate of genetic heterogeneity within the OI population to give a prior probability of linkage. This figure can then be modified for each family by additional information from concordant meioses.

Evaluation of inorganic pyrophosphate in amniotic fluid as a mode of prenatal diagnosis of osteogenesis imperfecta.

Using a modified procedure by Solomons and Styner (1969), an evaluation of inorganic pyrophosphate (PPi) was performed on the amniotic fluid of two fetuses at risk for osteogenesis imperfecta (OI) at 14 1/2 weeks gestation. The parents of both cases had a previous child with OI, Type II. The normal control group at 14-16 weeks gestation had PPi values ranging from 22.0-59.2 micrograms/100 ml, with a mean of 38.6 +/- 9.51 micrograms/100 ml. In each at-risk fetus, the amniotic fluid PPi value was within normal range. The first baby was born phenotypically normal at term. Intrauterine radiographic and fetal sonograms were done on the second fetus at approximately 19 weeks gestation. Both showed evidence of OI, Type II. The pregnancy was terminated at 21 weeks. Radiologic studies of the aborted fetus were consistent with OI, Type II. Our results indicate that the evaluation of PPi levels in amniotic fluid is not the method of choice for prenatal diagnosis of OI.

In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.

Sulfate (35SO4(-2)) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta "congenita," six patients with osteogenesis imperfecta "tarda," three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminolgycans in mutants as seen by the chase experimentas was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of 35SO4(-2) incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.