Thanatophoric dysplasia (TD) is caused by mutation of the gene that encodes fibroblast growth factor 3 (FGFR3). Owing to the poor prognosis for TD, prenatal diagnosis is critical to optimal perinatal management. We report here a case of TD in twin pregnancy, which was prenatally diagnosed by DNA analysis following amniocentesis at 15 weeks, and was managed by selective fetal termination. Prenatal ultrasonography and molecular analysis to detect TD-specific mutations enable accurate diagnosis of FGFR3-related TD in utero and appropriate obstetrical management at early gestation during twin pregnancy.
Amniocentesis ; Diagnosis ; DNA ; Female ; Fibroblast Growth Factor 3 ; Humans ; Pregnancy ; Pregnancy Reduction, Multifetal ; Pregnancy Trimester, Second* ; Pregnancy, Twin ; Prenatal Diagnosis ; Prognosis ; Thanatophoric Dysplasia* ; Twins* ; Ultrasonography, Prenatal

Thanatophoric dysplasia (TD) is a short-limb neonatal dwarfism syndrome that is usually lethal in the perinatal period. It is characterized by shortening of the limbs, severely small thorax, large head with a prominent forehead, macrocephaly, curved femur, and flattened vertebral bodies. These malformations result from the mutation in fibroblast growth factor receptor 3 (FGFR-3) gene which is located on the short arm of chromosome 4. A definite diagnosis should be established by molecular genetic analysis to find out the abnormal mutations in the FGFR3 gene. We confirmed by detection of a R248C mutation in the FGFR3 gene in DNA analysis.
Arm ; Chromosomes, Human, Pair 4 ; DNA ; Dwarfism ; Extremities ; Femur ; Forehead ; Head ; Macrocephaly ; Molecular Biology ; Receptor, Fibroblast Growth Factor, Type 3 ; Thanatophoric Dysplasia ; Thorax

Thanatophoric dysplasia (TD) is a lethal inherited skeletal disorder characterized by extremely short limbs, narrow chest, skull deformity and underdeveloped lungs. TD is divided into two types, depending primarily upon whether the bone in the upper leg (the femur) is curved or straight. We experienced two case of TD type I that were confirmed by clinical and radiological features after birth. Unlike previously reported cases of TD in our country, the multiple anomalies of CNS, kidney and cardiovascular system were identified in one of these cases.
Cardiovascular System ; Congenital Abnormalities ; Extremities ; Kidney ; Leg ; Lung ; Parturition ; Skull ; Thanatophoric Dysplasia ; Thorax ; Ultrasonography, Prenatal

Lethal skeletal dysplasia can be suspected at relatively early pregnancy by ultrasonography, but the final diagnosis is difficult to make. Genetic, histopathologic and radiologic examinations are needed for the diagnosis. The most common lethal skeletal dysplasia is thanatophoric dysplasia (TD) and which can be subdivided into two types according to its clinical features. Advances in prenatal ultrasound techniques, especially 3D multislice scan technique enable to get adequate plans to diagnose TD. We report one case of thanatophoric dysplasia type I diagnosed by new 3D multislice view technique and confirmed by histopathologic, genetic, radiologic examination after termination at 20 weeks of gestation.
Diagnosis ; Pregnancy ; Thanatophoric Dysplasia* ; Ultrasonography

Thanatophoric dysplasia is a lethal skeletal dysplasia due to the dysfunction of endochondral ossification characterized by short limbs, narrow chest, micromelia, cranial dysplasia. Tavormina described in 1995 that the dysfunction of endochondral ossification is due to the missence mutation of the gene presenting the Fibrblast Growth Factor Receptor 3. Thanatophoric dysplasia is classified as two types. The type I is characterized by the curved short limbs and severe platyspondyly, and the type II by the kleeblattschadel (cloverleaf deformity) and straight short limbs. Both are destined to the death a few days after the delivery due to the pulmonary hypoplasia from the hypoplastic thorax. We experienced a case of thanatophoric dysplasia on antenatal ultrasound examination and then pregnancy was terminated by vaginal delivery. Now, with the review of literature, we report the case of thanatophoric dysplasia confirmed by clinical features and radiological finding.
Extremities ; Pregnancy ; Thanatophoric Dysplasia* ; Thorax ; Ultrasonography

Skeletal dysplasias, a heterogenous group of bone growth disorders including thanatophoric dysplasia 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 a case of the type I thanatophoric dysplasia diagnosed specifically and terminated in the 2nd trimester.
Bone Development ; Diagnosis ; Molecular Biology ; Prognosis ; Thanatophoric Dysplasia* ; Ultrasonography

Twin gestations complicated by a single anomalus fetus present difficulties in obstetric management. It is unclear how the presence of a congenital anomaly in one twin affects its normal sibling. Parents may elect for obstetric management option such as expectant management or selective termination of the anomalous fetus in the hope maximizing the outcome for the normal co-twin. Thanatophoric dysplasia (TD) is the most common type of lethal skeletal dysplasia. Features of the disease are micromelic shortening of the limbs, relative macrocephaly with frontal bossing, flattened vertebrae, disorganized chondrocytes and trabeculae in the growth plates of the long bones, and shortened ribs resulting in a reduced thorax and a bell-shaped abdomen. We experienced a case of TD type I diagnosed in a dizygotic twins by ultrasound at 23 weeks' gestation and reported with concerned literatures.
Abdomen ; Chondrocytes ; Extremities ; Fetus ; Growth Plate ; Hope ; Humans ; Insemination* ; Macrocephaly ; Parents ; Pregnancy ; Ribs ; Siblings ; Spine ; Thanatophoric Dysplasia* ; Thorax ; Twins, Dizygotic* ; Ultrasonography

The early and accurate antenatal diagnosis of fetal musculoskeletal malfomations with a poor outcome has important implications for the management of a pregnancy. Careful ultrasonographic examination of a fetus helps detect such anomalies, and a number of characteristic features may suggest possible differential diagnoses. During the last five years, we have encountered 39 cases of such anomalies, and the typical prenatal ultrasonographic and pathologic findings of a number of those are described in this article.
Chondrodysplasia Punctata/diagnosis ; Female ; Fetal Diseases/*diagnosis ; Human ; Musculoskeletal Abnormalities/*diagnosis/radiography/ultrasonography ; Osteogenesis Imperfecta/diagnosis ; Pregnancy ; Pregnancy Outcome ; *Prenatal Diagnosis ; Thanatophoric Dysplasia/diagnosis ; *Ultrasonography, Prenatal

BACKGROUND: Achondroplasia is the most common form of dwarfism. The achondroplasia class consists of achondroplasia, thanatophoric dysplasia and hypochondroplasia. Clinical symptoms are variable, but the common gene, fibroblast growth factor receptor 3 (FGFR3), could account for these variable conditions. We tried to isolate the molecular defects in Korean patients with achondroplasia and hypochondroplasia. METHODS: The sites frequently mutated (G380R and N540K) of the FGFR3 gene of seventeen Korean patients with skeletal dysplasia (16 cases of achondroplasia and one of hypochondroplasia) were analyzed by PCR-RFLP and confirmed by direct sequencing. RESULTS: Missense mutations, which cause G380R of the FGFR3, were present in 15/16 (93.7%) achondroplasia patients. Among these, G to A transition was found in 14 of the 15 (93.3%) patients, and a G to C transversion in a single (6.6%) patient. One case did not show any mutation of the FGFR3 gene reported in achondroplasia, including G375C. A patient with suspected hypochondroplasia exhibited the common C to G transversion mutation, resulting in N540K. CONCLUSIONS: The mutations at codons 380 and 540 of the FGFR3 gene were also found to be common causative mutations of achondroplasia and hypochondroplasia, respectively, in Koreans. These mutations could be used as the target of molecular diagnosis. Based on this simple molecular study, genetic counseling for skeletal dysplasia and prenatal diagnosis will be possible.
Achondroplasia* ; Codon ; Diagnosis ; Dwarfism ; Fibroblast Growth Factors* ; Fibroblasts* ; Genetic Counseling ; Humans ; Mutation, Missense ; Prenatal Diagnosis ; Receptor, Fibroblast Growth Factor, Type 3* ; Receptors, Fibroblast Growth Factor* ; Thanatophoric Dysplasia

Osteochondrodysplasia is a heterogeneous group of disorders appearing short limbed dwarfism. Because many of these entities are lethal and hereditary, an accurate diagnosis is mandatory. The purpose of this study is to define the clinicopathologic features and radiologic findings of osteochondrodysplasia. We reviewed 29 autopsy cases of congenital short limbed dwarfism, consisting of thanatophoric dysplasia (TD) (12 cases), osteogenesis imperfecta (OI) (12 cases), asphyxiating thoracic dysplasia (ATD) (3 cases), short-rib-polydactyly syndrome (SRPS) (1 case) and hypochondrogenesis (1 case). The gestational age ranged from 16 to 41 weeks. Of 6 fetuses that were born alive, 3 were ATD, 2 were TD and 1 was hypochondrogenesis. TD was frequently complicated by hydramnios. Of 8 cases studied chromosomally, only 1 showed chromosomal abnormality -46XY, inv 9. Intrauterine growth retardation was frequently associated with OI. Pulmonary hypoplasia was present in 23 cases (79%), including all cases of ATD, SRPS and hypochondrogenesis, 11 in TD and 7 in OI. Other associated anomalies were present in 17 cases (59%).
Autopsy* ; Chromosome Aberrations ; Diagnosis ; Dwarfism ; Extremities ; Fetal Growth Retardation ; Fetus ; Gestational Age ; Osteochondrodysplasias* ; Osteogenesis Imperfecta ; Polyhydramnios ; Thanatophoric Dysplasia