Diagnosis Of Thanatophoric Dysplasia Research Articles

Diagnosis of thanatophoric dysplasia using clinical exome screening.

Bone dysplasias are a broad, heterogeneous group of diseases. Thanatophoric dysplasia is a rare bone dysplasia, but it is the most common lethal skeletal dysplasias. The major role in diagnostics plays a high-quality ultrasound examination in the 2nd trimester and the latest methods of genetic testing, including clinical exome testing. Knowing the correct diagnosis is crucial for the future of the fetus and the couple.

A Rare Case: Genetically Confirmed Newborn with Thanatophoric Dysplasia Type 1 (TD1)

Thanatophoric dysplasia (TD) is the most frequent sporadic lethal skeletal dysplasia with an incidence about 1 in 17.000–50.000 births. Diagnosis of TD can made at prenatal period by ultrasound and immediately after birth based on clinical examination, radiologic studies, histopathology and molecular analysis. Thanatophoric dysplasia is subdivided in two dinstinct phenotypes: 1) Thanatophoric dysplasia type 1 (TD1) is characterized by curved ‘‘telephone receiver’’ femora and mild craniosynostosis or 2) Thanatophoric dysplasia type 2 (TD2) includes straight femora and cloverleaf skull. Girl baby was born from 44 years old female with 35th weeks of gestation (WOG) with non-consanguineous marriage. The patient looked lethargic accompanied with rapid breathing with chest indrawing. On examination the patient looked dysmorphic, large head with frontal bossing without clover leaf skull, upper and lower limbs were extremely short. Babygram showed head was large, thoracic cavity was small and narrow, the ribs were short, and “telephone receiver” like curved femora was noted. Mutational analysis confirmed a heterozygous allele p.Tyr373Cys mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. The patient was diagnosed with TD1. The general condition and respiratory distress did not improve and the patient was died on the sixteenth days of hospitalization. Thanatophoric dysplasia type 1 was rare disease and lethal case. The diagnosis based on clinical examination, radiologic studies, histopathology and molecular analysis. Lethality in thanatophoric dysplasia is caused mainly by respiratory distress due to a narrow thorax.

Fetal thanatophoric dysplasia

Thanatophoric dysplasia (TD) is a rare autosomal dominant lethal skeletal dysplasia with two subtypes. Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) results in both subtypes. In prenatal diagnosis of TD by three-dimensional ultrasound examination in second trimester aids in visualizing facial features and other soft tissue findings such as cloverleaf skull, very short extremities and small thorax. Most of the affected fetuses die in utero or shortly after birth due to either respiratory insufficiency or brain stem compression or combination of both. We report one such rare case of type I TD encountered at 32 weeks of gestational age.

Thanatophoric dysplasia: possibilities of prenatal ultrasound diagnosis. Part 2. Temporal lobe dysplasia

Thanatophoric dysplasia (TD) is the most common type of lethal skeletal dysplasia. Differential diagnosis of TD (type I) is not always possible. In recent years, the possibility of ultrasound diagnosis of fetal temporal lobe dysplasia (TLD) as a sign of TD verification. Echographic diagnosis of TLD and ultrasound signs of abnormal sulcations in 3 fetuses with lethal signs of dysplasia at 20–24 weeks of gestation are presented. Issues ability of prenatal diagnosis of temporal lobe dysplasia are discussed.

Thanatophoric dysplasia: possibilities of early prenatal ultrasound diagnosis

We reviewed cases of early prenatal diagnosis of thanatophoric dysplasia (TD). Usually ТD is diagnosed at ultrasonic in the second-trimester scan. At first trimester the sonographic traditional signs of TD meet rarely. Often TD to be associated with increased nuchal translucency at first-trimester screening. TD may not be clearly distinguished from the other skeletal dysplasias in a first trimester. A definite diagnosis can be established by molecular genetic analysis.

Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric dysplasia

To determine the incidence of temporal lobe dysplasia (TLD) detected on prenatal ultrasound in thanatophoric dysplasia (TD) over an 11-year period in a tertiary referral center. An 11-year retrospective review of perinatal autopsies from 2002 to 2013 was performed to identify cases of TD. The ultrasound images and corresponding reports of all TD cases were examined for the presence of TLD. The same set of images subsequently underwent a retrospective review by a perinatal radiologist with knowledge of the features of TLD to determine whether they could be identified. Thirty-one cases of TD underwent perinatal autopsy, and prenatal ultrasound imaging was available for review in 24 (77%). Mean gestational age at diagnosis of TD was 21.3 (range, 18-36) weeks. TLD was identified and reported in 6/24 (25%) cases; all six cases occurred after 2007. Retrospective interpretation of the ultrasound images identified features of TLD in 10 additional cases. In total, 16/24 (67%) cases displayed sonographic evidence of TLD. Temporal trends showed that TLD features were present in 50% (5/10) of all TD cases between 2002 and 2006 and in 79% (11/14) of those detected between 2007 and 2013. At present, the detection rate of TLD by ultrasound is low but may be increased by modified brain images that enhance visualization of the temporal lobes. Prenatal identification of TLD may help in the prenatal diagnosis of TD and thus provide more accurate prenatal counseling and guide molecular investigations to confirm the specific diagnosis of TD.

Thanatophoric dysplasia in a dichorionic twin confirmed by genetic analysis at the early second trimester: A case report and literature review

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.

Diagnosis and counseling of thanatophoric dysplasia with four-dimensional ultrasound

Thanatophoric dysplasia is a severe skeletal disorder with estimated frequency of 0.2–0.5 per 10,000 births. Affected infants die shortly after birth. The diagnosis of thanatophoric dysplasia can be made by two-dimensional ultrasound but the perception of these images is very difficult for the patients. The use of four-dimensional real time ultrasound gives the physician the possibility to discuss and counsel the patients with images that are more understandable to the general public.

Rapid Detection of Common Mutations of the FGFR3 Gene Causing Thanatophoric Dysplasia Type I: Two Case Reports

Thanatophoric dysplasia (TD) is a relatively common lethal skeletal dysplasia. These malformations result from the mutations in fibroblast growth factor receptor 3 (FGFR3) gene, which is located on the short arm of chromosome 4. Accurate diagnosis of fetal TD is important for patient counseling and to plan the management. A definite diagnosis can be established by molecular genetic analysis to find out the abnormal mutations in the FGFR3 gene. We reported on two cases of TD type I found by prenatal ultrasound and confirmed by molecular analysis of FGFR3 gene using high-resolution melting analysis.

OP38.04: New aids to the prenatal diagnosis of thanatophoric dysplasia

OP38.04: New aids to the prenatal diagnosis of thanatophoric dysplasia

Diagnóstico pré-natal de displasia tanatofórica: papel do ultrassom fetal

OBJETIVO: Relatar o caso de um paciente com displasia tanatofórica, uma forma autossômica dominante e letal de nanismo, diagnosticado ainda no período pré-natal, e revisar a literatura, discutindo os principais diagnósticos diferenciais e ressaltando a importância do ultrassom fetal na identificação de fetos portadores dessa displasia. DESCRIÇÃO DO CASO: O paciente é o segundo filho de pais jovens sem história familiar de doenças genéticas. O ultrassom fetal realizado com 35 semanas de gestação mostrou polidrâmnio, proeminência frontal e desproporção entre crânio e tronco, com hipoplasia torácica e encurtamento dos ossos longos, compatível com o diagnóstico de displasia tanatofórica. Ao nascimento, a criança era pequena e possuía hipotonia, macrocefalia, fontanelas amplas, hipoplasia de face média, olhos protrusos, hemangioma plano no nariz e pálpebras, nariz em sela, micrognatia, pescoço e tórax curtos e encurtamento importante de braços, antebraços, coxas e pernas. A avaliação radiográfica mostrou crânio com grande diâmetro transverso, tórax com costelas curtas e corpos vertebrais reduzidos, importante encurtamento e deformidade dos ossos longos dos membros superiores e inferiores (os fêmures eram curvos) e hipoplasia da bacia. Esses achados confirmaram o diagnóstico pré-natal de displasia tanatofórica. O paciente evoluiu para o óbito poucos dias após o nascimento devido à insuficiência respiratória. COMENTÁRIOS: A ultrassonografia fetal é um método não invasivo capaz de diagnosticar inúmeras displasias ósseas, incluindo a tanatofórica. A importância do diagnóstico intra-útero reside no fato de que auxilia no diagnóstico diferencial, e permite o aconselhamento genético à família.

Thanatophoric dysplasia: Role of 3‐dimensional sonography

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. 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. 3D sonography can detect fetal TD and provide additional vivid illustration after various modes of reconstruction that 2D sonography cannot afford. 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.

P33.09: 3D ultrasound, MRI and molecular diagnosis of thanatophoric dysplasia type I

Skeletal dysplasias are a heterogeneous group of bone growth disorders with different fetal outcomes. Prenatal sonographic examination is an excellent method for discovering fetal skeletal dysplasias. However, it is not always possible to differentiate TD from others skeletal dysplasias by ultrasonography alone and molecular genetic analysis of the fibroblast growth factor receptor 3 (fgfr3) gene is useful for prenatal diagnosis of TD. Therefore definitive diagnosis should always be accomplished by a comprehensive postnatal evaluation, including clinical, radiological, pathological, biochemical and molecular genetic examination. Thanatophoric dysplasia (TD) is the most common form of platyspondylic lethal skeletal dysplasias and TD 1 is characterized by short limbs, a narrow thoracic cage, straight femora, with or without a cloverleaf skull. In this report, one fetus with TD 1 was diagnosed by 3D ultrasound and MRI in the second trimester, and molecular analyses of the fgfr3 gene confirmed the postnatal diagnosis.

Prenatal diagnosis and molecular analysis of type 1 thanatophoric dysplasia

Thanatophoric dysplasia (TD) is one of the most common lethal skeletal dysplasias with an estimated frequency of nearly 1 in 20000 births. It is characterized by extreme rhizomelia i.e. a normal trunk length but a narrow chest and a large head with a prominent forehead. The abnormality is classified into TD type 1 (TD 1) where patients always have curved femurs and sometimes a cloverleaf skull and TD type 2 (TD 2) where patients always have straight femurs and always a cloverleaf skull. The prenatal diagnosis of TD can be established by ultrasonography in the second trimester of gestation. However it is not always possible to differentiate TD from others skeletal dysplasias by ultrasonography alone and molecular genetic analysis of the fibroblast growth factor receptor 3 (fgfr3) gene is useful for prenatal diagnosis of TD. In this report 3 fetuses with TD 1 were diagnosed ultrasonographically in the second trimester and molecular analyses of the fgfr3 gene confirmed the prenatal diagnoses. (excerpt)