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1.
Pediatr Radiol ; 31(1): 27-30, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11200994

ABSTRACT

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.


Subject(s)
Prenatal Diagnosis , Thanatophoric Dysplasia/diagnostic imaging , Thanatophoric Dysplasia/pathology , Edema/complications , Fatal Outcome , Female , Humans , Pregnancy , Radiography , Thanatophoric Dysplasia/complications
2.
J Clin Endocrinol Metab ; 84(10): 3713-20, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10523019

ABSTRACT

Blomstrand osteochondrodysplasia (BOCD) is a rare lethal skeletal dysplasia characterized by accelerated endochondral and intramembranous ossification. Comparison of the characteristics of BOCD with type I PTH/PTH-related peptide (PTHrP) receptor-ablated mice reveals striking similarities that are most prominent in the growth plate. In both cases, the growth plate is reduced in size due to a strongly diminished zone of resting cartilage and the near absence of columnar arrangement of proliferating chondrocytes. This overall similarity suggested that an inactivating mutation of the PTH/PTHrP receptor might be the underlying genetic defect causing BOCD. Indeed, inactivating mutations of the PTH/PTHrP receptor have been recently identified in two cases of BOCD. We describe here a novel inactivating mutation in the PTH/PTHrP receptor. Sequence analysis of all coding exons of the type I PTH/ PTHrP receptor gene and complementary DNA of a case with BOCD identified a homozygous point mutation in exon EL2 in which one nucleotide (G at position 1122) was absent. The mutation was inherited from both parents, supporting the autosomal recessive nature of the disease. The missense mutation resulted in a shift in the open reading frame, leading to a truncated protein that completely diverged from the wild-type sequence after amino acid 364. The mutant receptor, therefore, lacked transmembrane domains 5, 6, and 7; the connecting intra- and extracellular loops; and the cytoplasmic tail. Functional analysis of the mutant receptor in COS-7 cells and of dermal fibroblasts obtained from the case proved that the mutation was indeed inactivating. Neither the transiently transfected COS-7 cells nor the dermal fibroblasts responded to a challenge with PTH or PTHrP with a rise in intracellular cAMP levels, in sharp contrast to control cells. Our results provide further evidence that BOCD is caused by inactivating mutations of the type I PTH/PTHrP receptor and underscore the importance of this receptor in mammalian skeletal development.


Subject(s)
Fetus/anatomy & histology , Fetus/physiology , Frameshift Mutation , Osteochondrodysplasias/genetics , Receptors, Parathyroid Hormone/genetics , Adult , Amino Acid Sequence/genetics , Animals , Base Sequence/genetics , COS Cells , DNA Mutational Analysis , Female , Growth Plate/embryology , Growth Plate/pathology , Humans , Humerus/embryology , Humerus/pathology , Molecular Sequence Data , Mutation, Missense , Osteochondrodysplasias/pathology , Pregnancy , Receptor, Parathyroid Hormone, Type 1
3.
Ultrasound Obstet Gynecol ; 11(4): 298-302, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9618859

ABSTRACT

The early second-trimester sonographic diagnosis of two infants with short rib (polydactyly) dysplasia type IV (Beemer-Langer dysplasia) is presented. In addition to short ribs, this syndrome is characterized by short limbs with or without polydactyly. There are often associated defects, particularly neural-tube anomalies. The occurrence of consanguinity and of four affected siblings in this family support autosomal recessive inheritance.


Subject(s)
Fetal Diseases/diagnostic imaging , Short Rib-Polydactyly Syndrome/diagnostic imaging , Ultrasonography, Prenatal , Adult , Biometry , Consanguinity , Female , Humans , Pregnancy , Short Rib-Polydactyly Syndrome/genetics
4.
Ultrasound Obstet Gynecol ; 9(6): 392-7, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9239824

ABSTRACT

We investigated the development of the skeleton in the embryonic and early fetal period both with ultrasonography and radiology. Eight normal embryos/fetuses were studied weekly with real-time transvaginal sonography between 8 and 16 weeks of gestation to establish the ultrasonographic characteristics of normal ossification. Additionally, ossification was studied in radiographs obtained from five embryos/fetuses between 9 and 14 weeks of gestation. Ossification centers, visualized as increased echogenicity of the bone, were recognized with ultrasonography from 9 weeks onwards. The appearance of primary ossification centers as observed by transvaginal ultrasonography was at the same gestational age or at most 1 week later than when obtained with radiography or whole-specimen staining techniques. Transvaginal ultrasonography enables early visualization of ossification centers in the embryo and fetus. Detailed knowledge of the development of ossification of the skeleton may contribute to early prenatal diagnosis of skeletal dysplasias.


Subject(s)
Bone Development , Bone and Bones/diagnostic imaging , Embryonic and Fetal Development , Osteogenesis , Ultrasonography, Prenatal , Bone and Bones/embryology , Endosonography/methods , Female , Gestational Age , Humans , Osteogenesis/physiology , Pregnancy , Radiography , Vagina/diagnostic imaging
5.
Am J Med Genet ; 73(3): 345-50, 1997 Dec 19.
Article in English | MEDLINE | ID: mdl-9415697

ABSTRACT

Blomstrand chondrodysplasia is a rare lethal skeletal dysplasia with presumed autosomal-recessive inheritance. A family with 2 affected fetuses was studied. One fetus demonstrated a severe skeletal dysplasia at routine transabdominal ultrasound examination at 18.5 weeks of gestation. The pregnancy was terminated and the diagnosis of Blomstrand chondrodysplasia was made at autopsy. A second affected fetus was identified by first-trimester transvaginal ultrasound at 12 weeks of gestation. In this case the diagnosis was confirmed by posttermination radiography and histopathology. From these observations, Blomstrand chondrodysplasia seems like a lethal rhizo/mesomelic short-limb, early-onset dysplasia with autosomal-recessive inheritance. Easy detectability by transvaginal ultrasound is demonstrated, but general applicability awaits further studies on the intra- and interfamilial variability of this disorder.


Subject(s)
Osteochondrodysplasias/genetics , Prenatal Diagnosis , Adult , Consanguinity , Female , Fetal Death/genetics , Fetal Death/pathology , Genes, Recessive , Humans , Osteochondrodysplasias/diagnostic imaging , Osteochondrodysplasias/pathology , Pregnancy , Pregnancy Trimester, First , Ultrasonography
6.
Hum Genet ; 98(6): 657-61, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8931695

ABSTRACT

Mutations in the diastrophic dysplasia sulfate transporter gene DTDST have been associated with a family of chondrodysplasias that comprises, in order of increasing severity, diastrophic dysplasia (DTD), atelosteogenesis type 2 (AO2), and achondrogenesis type 1B (ACG1B). To learn more about the molecular basis of DTDST chondrodysplasias and about genotype-phenotype correlations, we studied fibroblast cultures of three new patients: one with AO-2, one with DTD, and one with an intermediate phenotype (AO2/DTD). Reduced incorporation of inorganic sulfate into macromolecules was found in all three. Each of the three patients was found to be heterozygous for a c862t transition predicting a R279W substitution in the third extracellular loop of DTDST. In two patients (DTD and AO2/DTD), no other structural mutation was found, but polymerase chain reaction amplification and single-strand conformation polymorphism analysis of fibroblast cDNA showed reduced mRNA levels of the wild-type DTDST allele: these two patients may be compound heterozygotes for the "Finnish" mutation (as yet uncharacterized at the DNA level), which causes reduced expression of DTDST. The third patient (with AO2) had the R279W mutation compounded with a novel mutation, the deletion of cytosine 418 (delta c418), predicting a frameshift with premature termination. Also the delta c418 allele was underrepresented in the cDNA, in accordance with previous observations that premature stop codons reduce mRNA levels. The presence of the DTDST R279W mutation in a total of 11 patients with AO2 or DTD emphasizes the overlap between these conditions. This mutation has not been found so far in 8 analyzed ACG1B patients, suggesting that it allows some residual activity of the sulfate transporter.


Subject(s)
Carrier Proteins/genetics , Exostoses, Multiple Hereditary/genetics , Sulfates/metabolism , Anion Transport Proteins , Biological Transport/genetics , Cells, Cultured , DNA Mutational Analysis , Exostoses, Multiple Hereditary/pathology , Fibroblasts/metabolism , Genotype , Humans , Infant, Newborn , Male , Membrane Transport Proteins , Phenotype , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Sulfate Transporters
9.
Clin Dysmorphol ; 2(1): 1-19, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8298733

ABSTRACT

Data on twenty-two infants with lethal neonatal short-limbed platyspondylic dysplasia are reported. Thanatophoric dysplasia (TD) is the most frequent diagnosis in this group. TD combined with a cloverleaf skull (CS), has been variably classified. TD type 1 with curved femora is rarely combined with CS; TD type 2 with straight femora is almost always associated with CS. Other varieties of TD, known as 'Torrance', 'San Diego' or 'Luton' types, are separate entities. Apart from the differences in radiography and osteochondrohistology, the temporal-lobe abnormalities seen in TD were absent in one of the cases of the 'Torrance' variety. There were also differences in the composition of the cartilage glycosaminoglycans between this case and TD. Nearly all of the cases of these different types mentioned in the literature, including those of this study group, have been sporadic and may result from new dominant mutations. Documentation and classification by full (postmortem) radiography and osteochondrohistology is essential for two reasons. It will be the foundation for the clinical geneticist to inform the parents about the risk of recurrence. It will also be the basis for a biochemical or molecular-biological classification in the near future.


Subject(s)
Fetal Diseases/pathology , Osteochondrodysplasias/pathology , Prenatal Diagnosis , Thanatophoric Dysplasia/pathology , Brain/pathology , Female , Fetal Diseases/classification , Fetal Diseases/diagnostic imaging , Gestational Age , Glycosaminoglycans/blood , Growth Plate/pathology , Humans , Limb Deformities, Congenital , Male , Osteochondrodysplasias/classification , Osteochondrodysplasias/diagnostic imaging , Pregnancy , Radiography , Thanatophoric Dysplasia/classification , Thanatophoric Dysplasia/diagnostic imaging , Ultrasonography, Prenatal
10.
Eur J Immunol ; 20(7): 1483-9, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2201547

ABSTRACT

In the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA-452, a high endothelial-specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut-associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44-. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large-scale influx of lymphocytes occurred, it paralleled HEV development. HECA-452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the cortico-medullary junction expressed the HECA-452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus.


Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation/metabolism , Endothelium, Lymphatic/immunology , Endothelium/immunology , Lymphocytes/physiology , Lymphoid Tissue/growth & development , Antibodies, Monoclonal , Antigens, Surface/metabolism , Cell Movement/immunology , DiGeorge Syndrome/immunology , Gestational Age , Humans , Infant, Newborn , Lymph Nodes/embryology , Lymph Nodes/growth & development , Lymphoid Tissue/cytology , Lymphoid Tissue/embryology , Palatine Tonsil/embryology , Palatine Tonsil/growth & development , Receptors, Lymphocyte Homing , Thymus Gland/embryology , Thymus Gland/growth & development
11.
Prenat Diagn ; 10(5): 279-88, 1990 May.
Article in English | MEDLINE | ID: mdl-2201963

ABSTRACT

Radial-ray reduction malformations (RRRMs) may occur isolated or in association with other anomalies. The data of seven fetuses born with RRRMs were collected. Six fetuses had associated lethal abnormalities of the central nervous system, urogenital system, and/or heart, detected by ultrasound. In five cases, it was possible to establish the precise diagnosis, enabling an informed prognosis and subsequent genetic counselling. The diagnoses were: Edwards syndrome (n = 3), VACTERL association (n = 1), and Poland-Moebius-like complex (n = 1). In two cases, a complete diagnosis was not possible because of inadequate evaluation of these fetuses before and/or after birth. A proposal is given for the diagnostic approach for infants with RRRMs detected in the antenatal period by means of ultrasonography.


Subject(s)
Abnormalities, Multiple/diagnosis , Bone and Bones/abnormalities , Prenatal Diagnosis , Abnormalities, Multiple/genetics , Adolescent , Adult , Chromosomes, Human, Pair 18 , Diagnosis, Differential , Female , Hand Deformities, Congenital/diagnosis , Heart Defects, Congenital/diagnosis , Humans , Nervous System Malformations , Pregnancy , Radius/abnormalities , Trisomy , Ulna/abnormalities , Ultrasonography , Urogenital Abnormalities
12.
Pediatr Radiol ; 21(1): 52-6, 1990.
Article in English | MEDLINE | ID: mdl-2287542

ABSTRACT

Post-mortem radiography of fetuses with skeletal dysplasia is essential for diagnostic classification. Interpretation of the radiographs should be based on the knowledge of morphology and dimensions of the normal skeleton in all stages of development. A retrospective post-mortem radiographic study is presented with measurements of the lengths of the long bones and thoracic and lumbar spine. The study included 69 fetuses and neonates with a normal skeleton, whose gestational age ranged from 13-42 weeks and who died perinatally or lived for less than one week. The measurements of the long bones were plotted on growth curves obtained from a prospective longitudinal ultrasonographic investigation of another group of 63 normal fetuses from 12-40 weeks of gestation. Thoracic and lumbar spine measurements by ultrasonography were not available. The radiographic data of thoracic and lumbar spine were, therefore, compared to radiographic studies from the literature. No disagreement with these studies was found. It can be concluded that measurements of bones from standardized post-mortem radiographs in cases of questionable gestational age or defects of bone development can be compared with ultrasonographic measurements. To illustrate the usefulness of the graphs, 13 fetuses with various types of skeletal dysplasia were evaluated retrospectively.


Subject(s)
Bone and Bones/embryology , Embryonic and Fetal Development , Bone Diseases, Developmental/diagnostic imaging , Bone Diseases, Developmental/embryology , Bone and Bones/diagnostic imaging , Cross-Sectional Studies , Female , Femur/diagnostic imaging , Femur/embryology , Gestational Age , Humans , Infant, Newborn , Longitudinal Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/embryology , Pregnancy , Radiography , Retrospective Studies , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/embryology , Ultrasonography, Prenatal
13.
Am J Obstet Gynecol ; 159(1): 176-81, 1988 Jul.
Article in English | MEDLINE | ID: mdl-3293447

ABSTRACT

Between 1982 and 1986, osteogenesis imperfecta was diagnosed by ultrasound in seven fetuses. The known heterogeneity of osteogenesis imperfecta was confirmed by the prenatal ultrasonographic findings. Dependent on the type of osteogenesis imperfecta, the appearance of the limbs varied from severely shortened and broad, with very low echogeneity and absent acoustic shadow (type IIA), to only moderately shortened and thin, with almost normal echogeneity and acoustic shadow but clearly visible fractures causing angulation of the bone (types IIC and III). Ultrasonography offers the possibility to detect or exclude the lethal and severe forms of osteogenesis imperfecta early (type IIA) or halfway (types IIB, IIC, and III) through the second trimester. Prenatal diagnosis of the disease allows the option of elective abortion or may prevent unnecessary obstetric intervention.


Subject(s)
Fetal Diseases/diagnosis , Osteogenesis Imperfecta/diagnosis , Prenatal Diagnosis , Ultrasonography , Adult , Female , Gestational Age , Humans , Pregnancy
14.
Pediatr Pathol ; 8(6): 571-97, 1988.
Article in English | MEDLINE | ID: mdl-3072551

ABSTRACT

In the classification of lethal osteochondrodysplasias, achondrogenesis and hypochondrogenesis have recently received special attention. We describe 23 cases representing the different subtypes. Within the classical type I (Parenti-Fraccaro) two distinct disorders can be recognized: type IA (Houston-Harris) and type IB (Fraccaro). The classical type II (Langer-Saldino) and hypochondrogenesis represent phenotypic variants of one disorder in which type II is the most severe form and hypochondrogenesis the mildest form, while transitional forms exist. It is likely that a basic defect in cellular function of the chondrocyte results in a deficient cartilage matrix and in disorganized enchondral ossification.


Subject(s)
Osteochondrodysplasias/diagnosis , Thanatophoric Dysplasia/diagnosis , Bone Matrix/pathology , Bone and Bones/pathology , Cartilage/pathology , Female , Growth Plate/pathology , Humans , Infant, Newborn , Male , Pregnancy , Radiography , Terminology as Topic , Thanatophoric Dysplasia/diagnostic imaging , Thanatophoric Dysplasia/pathology , Ultrasonography
15.
Pediatr Pathol ; 8(3): 233-52, 1988.
Article in English | MEDLINE | ID: mdl-3050913

ABSTRACT

The radiologic and pathologic characteristics of 7 cases of lethal osteogenesis imperfecta (OI), diagnosed prenatally by ultrasound in the 15th to 34th week, are described. They include four variants of the Sillence classification: types IIA, IIB, IIC, and type III. The radiologic criteria that differentiate these types of OI are described. The histopathology of the bones differed only slightly in types IIA, IIB, and III; OI type IIC, however, differed markedly from the other types.


Subject(s)
Fetal Diseases/classification , Osteogenesis Imperfecta/classification , Female , Femur Head/embryology , Femur Head/pathology , Fetal Diseases/diagnosis , Fetal Diseases/diagnostic imaging , Fetal Diseases/pathology , Growth Plate/pathology , Humans , Male , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/diagnostic imaging , Osteogenesis Imperfecta/pathology , Pregnancy , Prenatal Diagnosis , Radiography , Ultrasonography
16.
Pediatr Pathol ; 5(3-4): 319-24, 1986.
Article in English | MEDLINE | ID: mdl-3786263

ABSTRACT

A rare observation was made in a 14-day-old infant with atresia of the urethra, vagina, and anus. Keratinized squamous cells from the vagina were found on peritoneal surfaces and in the peripheral sinuses of axillary lymph nodes. The mechanism of the transport of the squamous cells is briefly discussed.


Subject(s)
Lymph Nodes/cytology , Peritoneal Cavity/cytology , Urogenital Abnormalities , Abnormalities, Multiple/pathology , Female , Humans , Infant, Newborn , Phagocytosis , Twins, Monozygotic , Urogenital System/pathology
17.
Article in English | MEDLINE | ID: mdl-3097955

ABSTRACT

The existence of zonal aganglionosis, a rare variant of Hirschsprung's disease, is often questioned. An extensive enzyme and immunohistochemical study was performed on gut specimens of two patients presenting with bilious vomiting and abdominal distension to find evidence of the existence of double zonal aganglionosis and to characterize the abnormalities of the enteric nervous system. The hypotheses concerning the pathogenesis of this neurogenic disorder are reviewed. The results of our study confirm the existence of zonal aganglionosis. The clinical presentation may be similar to classical Hirschsprung's disease.


Subject(s)
Hirschsprung Disease/pathology , Acetylcholinesterase/analysis , Biopsy , Colon/pathology , Colostomy , Female , Hirschsprung Disease/enzymology , Histocytochemistry , Humans , Ileostomy , Ileum/pathology , Immunologic Techniques , Infant , Male , Muscles/pathology , Rectum/pathology
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