1/51. prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal skeletal dysplasia. Recently. mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II (TDII), have been identified. This discovery has now made it possible to make a definite diagnosis of TD by molecular methods. To date, prenatal diagnosis of TD has been accomplished by ultrasonography in the second trimester. However, it is not always possible to distinguish TD fetuses it utero from the other osteochondrodysplasias by ultrasonography or radiography. We report on the prenatal diagnosis of a TD fetus, showing severe shortness of limbs and polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic dna was isolated from the amniotic fluid and then subjected to PCR amplification. The common TDI mutation, C-->T transition at nucleotide 742 in the FGFR3 gene, was identified using restriction enzyme analysis. This information was critical in obstetric management decisions later in pregnancy. However, although the mutation responsible for TDI was detected previously, we noticed some inconsistencies in the published PCR results and have proposed a correction.- - - - - - - - - - ranking = 1keywords = dysplasia (Clic here for more details about this article) |
2/51. Camptomelic dysplasia: a case study.Camptomelic dysplasia (CMD) is a congenital short-limb skeletal dysplasia characterized by prenatal bowing of the lower limbs in association with additional anomalies of the tracheobronchial tree or genitourinary tract. Perinatal and early neonatal death from respiratory failure is common. Diagnosis and long-term management of the infant with CMD require a coordinated effort among many specialists. This article presents a general overview of skeletal dysplasias and camptomelic dysplasia. It concludes with a case study illustrating the many problems infants with CMD may have and the complex treatment and follow-up services they require.- - - - - - - - - - ranking = 1.1428571428571keywords = dysplasia (Clic here for more details about this article) |
3/51. Markers for bone metabolism in a long-lived case of thanatophoric dysplasia.We report a male patient with type 1 thanatophoric dysplasia, now eight years old, having a mutation in the FGFR3 gene. Radiological examination at birth revealed that the ribs and the bones of the extremities were very short and vertebral bodies were greatly reduced in height with wide intervertebral spaces. The femurs were shaped like French telephone receivers. Because of respiratory insufficiency due to the narrow thorax, the patient has been intubated and supported by continuous mechanical ventilation since the day after birth. Since 5 years of age, despite sufficient caloric intake, his body weight never increased above 4700 g, body height 49.0 cm, head circumference 46.1 cm, and chest circumference 35.8 cm. Acanthosis nigricance and huge bilateral coral-like urolithiases has been present. His mental development was severely retarded but he was able to make emotional expressions. Although developments in motor functions could not be assessed, his neurodevelopmental milestones in social relationships and language perception seemed to be at the level of a 10 to 12 month old. His bone maturation was also severely retarded. All of the assays of his serum and urinary bone formation- or resorption-related substances were within normal limits for age. Therefore, bone formation as well as bone resorption activities seemed normal and not responsible for his growth retardation.- - - - - - - - - - ranking = 0.71428571428571keywords = dysplasia (Clic here for more details about this article) |
4/51. Sonographic and molecular diagnosis of thanatophoric dysplasia type I at 18 weeks of gestation.thanatophoric dysplasia is the most common type of lethal skeletal dysplasia. It can usually be diagnosed with ultrasound, but differential diagnosis with other osteochondrodysplasias is not always possible. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been demonstrated to cause two distinct subtypes of the disorder. We describe a case of thanatophoric dysplasia type I diagnosed at 18 weeks of gestation by ultrasonography. Genomic dna obtained by chorionic villus sampling showed a C to G substitution at position 746 in the FGFR3 gene, resulting in a Ser249Cys substitution already known to be associated with type I disease. Implications for perinatal management are discussed.- - - - - - - - - - ranking = 1.1428571428571keywords = dysplasia (Clic here for more details about this article) |
5/51. Schneckenbecken dysplasia, radiology, and histology.To our knowledge this is the first report of Schneckenbecken dysplasia with the development of hydrops early in the second trimester. The radiological findings showed the typical hypoplastic iliac bones with medial extension and very flattened, on lateral view, oval-shaped vertebral bodies and short long bones. The histology showed hypercellular and hypervascular cartilage with chondrocytes with centrally located nucleus. The absence of the lacunar space as described before was also observed in some chondrocytes in our case. This male fetus was the product of consanguineous parents of Mediterranean origin compatible with autosomal recessive inheritance.- - - - - - - - - - ranking = 0.71428571428571keywords = dysplasia (Clic here for more details about this article) |
6/51. prenatal diagnosis and genetic analysis of type I and type II thanatophoric dysplasia.thanatophoric dysplasia (TD) is one of the most common neonatal lethal skeletal dysplasias. Prenatal sonographic and molecular genetic diagnoses of three cases of TD type I (TD1) and one case of TD type II (TD2) are presented here. Two fetuses of TD1 were characterized by polyhydramnios, macrocephaly, short limbs, a narrow thoracic cage and curved short femora, but without a cloverleaf skull at 27 and 31 weeks' gestation, respectively. The third fetus with TD1 was, however, not associated with macrocephaly, polyhydramnios, chest narrowing and severe femoral bowing on prenatal ultrasound at 18 weeks' gestation. The TD2 fetus was characterized by polyhydramnios, short limbs, a narrow thoracic cage, straight short femora, hydrocephalus and a cloverleaf skull at 24 weeks' gestation. Three-dimensional ultrasound was able to enhance the visualization of thickened, redundant skin folds and craniofacial and limb deformities associated with TD. Molecular analysis of the fibroblast growth factor receptor 3 (FGFR3) gene by restriction enzyme digestion analysis and direct sequencing using cultured amniotic fluid cells or cord blood cells revealed a missense mutation of 742C-->T (Arg248Cys) in all cases with TD1 and a missense mutation of 1948A-->G (Lys650Glu) in the case with TD2. The present report shows that adjunctive applications of molecular genetic analysis of the FGFR3 gene and three-dimensional ultrasound are useful for prenatal diagnosis of TD.- - - - - - - - - - ranking = 0.85714285714286keywords = dysplasia (Clic here for more details about this article) |
7/51. thanatophoric dysplasia type I.thanatophoric dysplasia is a sporadic, nearly always lethal congenital skeletal dysplasia. It is characterized by shortening of the limbs, a severely small thorax, macrocephaly, and platyspondyly. There are two major subtypes: a short, curved femur characterizes type I, and a straighter femur with cloverleaf skull characterizes type II. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR-3) gene have been identified in both subtypes, which suggest that thanatophoric dysplasia is a genetically homogenous skeletal disorder. Most affected neonates die of respiratory failure, due to narrow thorax with pulmonary hypoplasia. Antenatal sonographic diagnosis is feasible in the second trimester of pregnancy, but differentiating thanatophoric dysplasia from non-lethal skeletal disorders is very important. At the present time, however, prenatal genetic screening seems unpractical.- - - - - - - - - - ranking = 1.1428571428571keywords = dysplasia (Clic here for more details about this article) |
8/51. autopsy case of thanatophoric dysplasia: observations on the serial sections of the brain.The neuropathological findings in an autopsy case of thanatophoric dysplasia (TD) with serial sections of the brain are described here. This patient was a female infant, born at 33 weeks gestation, who died on day 1. Skeletal anomalies, consisting of short limbs, a small thorax, short ribs, thick cortical vertebral body substance and sternum substance, and hypoplastic lungs, were compatible with typical phenotypic features of TD. The brain weighed 370 g, showing a cloverleaf megalencephaly. A computerized 3-D reconstruction technique visualized clearly abnormal deep sulci arranged perpendicular to the neuraxis on the inferior surface of the temporal lobe, and peculiar configurational changes of the lateral ventricle. In particular, the inferior horn showed an unusual complex form. Dysgenetic changes were largely located in the anterior temporal lobe as follows: cortical polymicrogyria; leptomeningeal heterotopia with discontinuity of the subpial basement membrane; serpentine arrangement of pyramidal cells of the cornu ammonis (CA)1 of the hippocampus; hypoplastic dentate gyrus; hyperplasia of the amygdaloid body; and heterotopic nodules of neuroblasts or glioblasts in the periventricular white matter. Apart from the temporal lobe, the cerebral pia mater showed unusual fusion of two facing sheets in a sulcus and ectopia of nerve cells, and the cerebellar vermis was small. The findings observed here indicate that overgrowth and lack of growth can coexist in the TD brain, suggesting that some interaction(s) between the mesenchyme and the nervous tissue may play a role in normal differentiation of these two cell lines.- - - - - - - - - - ranking = 0.71428571428571keywords = dysplasia (Clic here for more details about this article) |
9/51. Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype.We report two patients with clinical and radiological findings of achondroplasia, who had the most common FGFR3 mutation occurring in thanatophoric dysplasia type I and hypochondroplasia, respectively. thanatophoric dysplasia is usually a lethal condition, but the patient carrying this mutation is alive and presents a medical history similar to that of patients with achondroplasia. The events leading to such a discrepancy between genotype and phenotype are unclear. These rare cases may influence an appropriate medical and genetic counseling.- - - - - - - - - - ranking = 0.85714285714286keywords = dysplasia (Clic here for more details about this article) |
10/51. Diagnosis of skeletal dysplasia by multidisciplinary assessment: a report of two cases of thanatophoric dysplasia.Skeletal dysplasias, a heterogeneous group of bone growth disorders, can be detected by routine prenatal ultrasound examination. As it is difficult to make a specific diagnosis, prediction of prognosis is of importance for obstetric management. In order to specify diagnosis, radiological, pathological and molecular genetic examination are often required. Our report describes two cases of thanatophoric dysplasia with different fetal sonographic findings. The classical classification of type I and II seems to be ambiguous as, in both cases, the same mutation in the fibroblast growth factor receptor 3 gene was found. The importance of comprehensive multidisciplinary assessment is emphasized.- - - - - - - - - - ranking = 1.4285714285714keywords = dysplasia (Clic here for more details about this article) |
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