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Pediatrics International : Official... 2023
Topics: Humans; Thanatophoric Dysplasia; Respiration, Artificial; Respiratory Function Tests; Receptor, Fibroblast Growth Factor, Type 3
PubMed: 36965046
DOI: 10.1111/ped.15534 -
Ultrasound in Obstetrics & Gynecology :... Jul 1996A series of three cases is reported in which the diagnosis of thanatophoric dysplasia was reached at routine mid-trimester scanning in a District General Hospital. All... (Review)
Review
A series of three cases is reported in which the diagnosis of thanatophoric dysplasia was reached at routine mid-trimester scanning in a District General Hospital. All three patients underwent termination of pregnancy with the diagnosis of thanatophoric dysplasia confirmed by postmortem radiographic and histological examinations. A review of the current literature on thanatophoric dysplasia is given, with special emphasis on the differentiation of the main types of thanatophoric dysplasia from other skeletal abnormalities.
Topics: Abortion, Induced; Adult; Diagnosis, Differential; Female; Humans; Osteochondrodysplasias; Pregnancy; Pregnancy Trimester, Second; Thanatophoric Dysplasia; Ultrasonography, Prenatal
PubMed: 8843623
DOI: 10.1046/j.1469-0705.1996.08010062.x -
AJR. American Journal of Roentgenology Jun 2010
Topics: Female; Humans; Imaging, Three-Dimensional; Pregnancy; Thanatophoric Dysplasia; Ultrasonography, Prenatal
PubMed: 20489076
DOI: 10.2214/AJR.09.3977 -
Journal of Medical Genetics Nov 1989
Topics: Diagnosis, Differential; Diseases in Twins; Humans; Infant, Newborn; Osteochondrodysplasias; Radiography; Thanatophoric Dysplasia; Twins; Twins, Monozygotic
PubMed: 2585471
DOI: 10.1136/jmg.26.11.735 -
Biophysical Journal Jan 2015Thanatophoric dysplasia type I (TDI) is a lethal human skeletal growth disorder with a prevalence of 1 in 20,000 to 1 in 50,000 births. TDI is known to arise because of...
Thanatophoric dysplasia type I (TDI) is a lethal human skeletal growth disorder with a prevalence of 1 in 20,000 to 1 in 50,000 births. TDI is known to arise because of five different mutations, all involving the substitution of an amino acid with a cysteine in fibroblast growth factor receptor 3 (FGFR3). Cysteine mutations in receptor tyrosine kinases (RTKs) have been previously proposed to induce constitutive dimerization in the absence of ligand, leading to receptor overactivation. However, their effect on RTK dimer stability has never been measured experimentally. In this study, we characterize the effect of three TDI mutations, Arg248Cys, Ser249Cys, and Tyr373Cys, on FGFR3 dimerization in mammalian membranes, in the absence of ligand. We demonstrate that the mutations lead to surprisingly modest dimer stabilization and to structural perturbations of the dimers, challenging the current understanding of the molecular interactions that underlie TDI.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Humans; Mutation, Missense; Protein Multimerization; Protein Stability; Receptor, Fibroblast Growth Factor, Type 3; Thanatophoric Dysplasia
PubMed: 25606676
DOI: 10.1016/j.bpj.2014.11.3460 -
Journal of Clinical Ultrasound : JCU Jan 2009Fetal thanatophoric dysplasia (TD) is a lethal skeletal dysplasia. Therefore, antenatal diagnosis of TD is mandatory in routine obstetrical care. However, because TD is...
PURPOSE
Fetal thanatophoric dysplasia (TD) is a lethal skeletal dysplasia. Therefore, antenatal diagnosis of TD is mandatory in routine obstetrical care. However, because TD is relatively rare, prenatal detection is not an easy task. In the past, 2-dimensional (2D) sonography had been applied as the mainstay of prenatal diagnosis of TD. In this series, we report our work of detecting TD using 3-dimensional (3D) sonography.
METHODS
We reviewed our computer database of prenatal diagnosis of TD in National Cheng Kung University Hospital from May 1995 to June 2006. All the cases were scanned using 2D and 3D sonography. In total, 9 cases of fetal TD were diagnosed.
RESULTS
3D sonography can detect fetal TD and provide additional vivid illustration after various modes of reconstruction that 2D sonography cannot afford.
CONCLUSION
3D sonography may contribute significantly to the detection of TD in utero and provide a novel visual depiction of this defect after reconstruction. Thus, 3D sonography may assist substantially in prenatal diagnosis as well as consultation.
Topics: Adult; Female; Humans; Imaging, Three-Dimensional; Pregnancy; Retrospective Studies; Thanatophoric Dysplasia; Ultrasonography, Prenatal; Young Adult
PubMed: 18837426
DOI: 10.1002/jcu.20526 -
Pediatrics International : Official... Aug 2019Thanatophoric dysplasia (TD) is a rare congenital disease of the skeletal system, with an incidence of 1.68-8.3 per 100 000 births, but statistical data on the...
BACKGROUND
Thanatophoric dysplasia (TD) is a rare congenital disease of the skeletal system, with an incidence of 1.68-8.3 per 100 000 births, but statistical data on the estimated number of TD patients across Japan are not available. The aim of this study was therefore to investigate the prevalence and prognosis of TD in Japan.
METHODS
A nationwide primary questionnaire survey was conducted.
RESULTS
A total of 127 obstetric, 186 pediatric, and 115 orthopedic facilities provided responses. Excluding duplications, we identified 73 patients with TD. Of the 73 cases, 15 were abortions, four were stillbirths, 51 were live births, and three had unknown details. Of the 51 live newborns, 27 died ≤7 days after birth, with an early neonatal mortality rate of 56%. Of the 24 newborns who survived the early neonatal period, 16 survived for ≥1 year. All of the 24 newborns received respiratory management and survived during the early neonatal period. Of the 51 live newborns, 25 did not receive respiratory management and died ≤2 days after birth.
CONCLUSIONS
The prevalence of TD in Japan is estimated to be at 1.1 (95%CI: 0.84-1.37) per 100 000 births, but the actual incidence is expected to be higher. To our knowledge, we have confirmed for the first time that newborns with TD may not always die during the early neonatal period but can survive the early neonatal period with appropriate respiratory management. Therefore, the term "thanatophoric dysplasia" does not accurately reflect the nature of the disease.
Topics: Adolescent; Child; Child, Preschool; Female; Health Surveys; Humans; Infant; Infant Mortality; Infant, Newborn; Japan; Male; Prevalence; Prognosis; Retrospective Studies; Thanatophoric Dysplasia; Young Adult
PubMed: 31247124
DOI: 10.1111/ped.13927 -
Acta Paediatrica Taiwanica = Taiwan Er... 2001Thanatophoric dysplasia is a sporadic, nearly always lethal congenital skeletal dysplasia. It is characterized by shortening of the limbs, a severely small thorax,...
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.
Topics: Female; Humans; Infant, Newborn; Mutation; Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor; Thanatophoric Dysplasia
PubMed: 11270184
DOI: No ID Found -
European Journal of Medical Genetics Mar 2021Three sibling fetuses identified with limb shortening and thoracic narrowing at twelve weeks' gestation on first trimester ultrasound examination are presented. The...
Three sibling fetuses identified with limb shortening and thoracic narrowing at twelve weeks' gestation on first trimester ultrasound examination are presented. The parents were non-consanguineous, Caucasian, healthy, of normal stature and had a healthy normal daughter. The radiographic abnormalities were highly suggestive of thanatophoric dysplasia, but molecular analysis failed to identify a pathogenic variant in FGFR3. The three fetuses were found to have identical compound heterozygous mutations in RMRP in trans, one inherited from the mother and one from the father. This represents the early prenatal presentation and fetal findings of metaphyseal dysplasia type McKusick (Cartilage-hair hypoplasia; CHH)/anauxetic dysplasia spectrum of disorders.
Topics: Adult; Diagnosis, Differential; Dwarfism; Female; Genetic Testing; Hair; Heterozygote; Hirschsprung Disease; Humans; Mutation; Osteochondrodysplasias; Pregnancy; Primary Immunodeficiency Diseases; RNA, Long Noncoding; Receptor, Fibroblast Growth Factor, Type 3; Thanatophoric Dysplasia; Ultrasonography, Prenatal
PubMed: 33567347
DOI: 10.1016/j.ejmg.2021.104162 -
Case Reports in Obstetrics and... 2016During a routine prenatal exam, a 36-year-old female in her third pregnancy was diagnosed with fetal hydrops at 11 weeks of gestation. The pregnancy was monitored with...
During a routine prenatal exam, a 36-year-old female in her third pregnancy was diagnosed with fetal hydrops at 11 weeks of gestation. The pregnancy was monitored with periodic ultrasounds; however, spontaneous resolution was not observed. Amniotic fluid examination at 16 weeks of gestation showed a normal karyotype; however, macrocephaly, a narrow thorax, and shortening of the long bones were observed on ultrasonography. With the strong suspicion of a fetal skeletal disease, specifically thanatophoric dysplasia (TD), and after extensive genetic counseling, termination of the pregnancy was performed per the parents' wishes with mechanical cervical dilation and gemeprost (PGE1) administration. Following delivery, the fetus was found to have macrocephaly, a narrow bell-shaped thorax, and a protuberant abdomen, as well as curved long bones, H-shaped platyspondyly, and curved clavicles on skeletal radiography. As a result, the fetus was diagnosed with TD type I. This case illustrates that although TD is a rare disease, an accurate prenatal diagnosis can be made with the use of ultrasonography.
PubMed: 27006844
DOI: 10.1155/2016/1821230