Thanatophoric dysplasia type 1 with temporal lobe dysplasia: Report of a case along with differential diagnosis.

Thanatophoric dysplasia type 1 (TD1) is a lethal form of osteochondral dysplasia due to mutation of FGFR3 gene. In addition to severe shortening of the limbs there is temporo-occipital lobe dysplasia along with a range of other CNS anomalies. In this report we describe the radiological and anatomical features at autopsy in neonate with TD1 along with the CNS anomalies. We have also summarized the key distinguishing features of TD1 from other common types of osteochondral dysplasia. An accurate diagnosis is important for genetic counseling and impact on future pregnancies.

A THANATOPHORIC DYSPLASIA TYPE I CASE WITH A FGFR3 P.R248C MUTATION AND SURVIVAL BEYOND THE NEONATAL PERIOD.

A Thanatophoric dysplasia, is a severe congenital anomaly which mostly causes stillbirth or death of the affected baby within hours due to respiratory insufficiency. The diagnosis of TD is typically suspected on ultrasound during the second trimester of pregnancy, when severe shortening of the long bones, frontal bossing, flattened vertebrae, and short ribs that result in a narrow thorax and bell-shaped abdomen, can be seen. Here, we present a case with prenatal ultrasonographic findings suggestive of TD, and highlight the patient's postnatal dysmorphic features and typical radiographic findings. The definitive diagnosis of TD type I (TDI) was made postnatally, when molecular genetic analysis revealed the previously described p.R248C mutation in FGFR3. This case is reported due to its relative long life span and the definitive molecular diagnosis that could be made during hospitalization.

The prevalence of thanatophoric dysplasia and lethal osteogenesis imperfecta type II in Northern Ireland - a complete population study.

The minimum prevalence of lethal Osteogenesis imperfecta type II, thanatophoric dysplasia and achondroplasia were derived following detailed case note review of all perinatal lethal skeletal dysplasias (SD) in Northern Ireland over a 12 year period. Multiple sources of ascertainment, including genetic notes, radiological reports and post mortem findings, were used. 39 cases were identified. Thanatophoric dysplasia was the commonest diagnosis made (22), followed by osteogenesis imperfecta type II (four children) and achondroplasia (two children). Eleven other diagnoses each occurred once in the 12 year period. The minimum prevalence range, per live births, of each of the common skeletal dysplasias in Northern Ireland has been calculated; thanatophoric dysplasia 0.80/10,000, osteogenesis imperfecta type II 0.15/10,000 and achondroplasia 0.07/10,000. The prevalence range for thanatophoric dysplasia is much higher than reported in previous studies. We discuss reasons for the prevalence figures obtained.

Displasia tanatoforica: reporte de un caso / Thanatophoric dysplasia: a case report

Este caso concierne a paciente de 15 años quien fue referida del medio rural por presentar en su control pre-natal hallazgo ecográfico de malformación congénita: Polihidramnios severo, edema fetal generalizado (anasarca) hidrops no inmune con antecedente de hermano con malformación esuquelética congénita acondroplasia. Fue estudiada en el Servicio de ARO, observándose durante su hospitalización ausencia de frecuencia cardiaca fetal razón por la cual, se realiza inducción de trabajo de parto con obtención de producto con signos de maceración además de malformaciones esqueléticas en miembros superiores e inferiores, edema generalizado, desprendimiento de placenta 20 por ciento. Posteriormente se realiza curetaje uterino para verificar presencia o no de restos placentarios, después de 2 días de hospitalización la paciente se egresa debido a buena evolución clínica.

Long-term survival in typical thanatophoric dysplasia type 1.

Thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always lethal neonatally, although a few previous reports have documented survival up to 4.75 years. We present a patient with survival beyond age 9 years and summarize his growth, development and medical history. The common Arg248Cys mutation in the extracellular region of fibroblast growth factor receptor 3 (FGFR3) was identified, eliminating the possibility that his long-term survival is attributable to an atypical mutation. This patient (and at least one other TD long-term survivor) have a rare skin disorder, acanthosis nigricans, which also occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.

[Fatal nanism: 3 different entities]. / Enanismos letales: tres entidades diferentes.

Three cases of congenital dwarfism are presented. All of them are lethal and represent the three better known nonviable nosologic entities: Achondrogenesis I, Achondrogesis II and Thanatophoric dwarfism. According to clinical features and radiologic data it is possible to approach the diagnosis accurately. We comment genetic, clinic, radiologic and histologic aspects of these processes. It is important to establish a differential diagnosis as these entities have different genetic basis, what influences genetic counsel.

Prevalence of lethal osteochondrodysplasias in Denmark.

The point prevalence at birth of lethal osteochondrodysplasias in a subregion of Denmark was estimated by a study of all children born January 1970 through December 1983. Two cases of thanatophoric dysplasia, one case of thanatophoric dysplasia with cloverleaf skull, two cases of micromelic bone dysplasia with cloverleaf skull, two cases of achondrogenesis type III, and three cases of achondrogenesis type IV were found. Two cases were unclassifiable due to lack of radiographs. In total, the point prevalence at birth was 15.4 per 100,000. Thus lethal osteochondrodysplasias seem to be more common than is generally assumed. The clinical and radiographic findings in micromelic bone dysplasia with cloverleaf skull are discussed in relation to thanatophoric dysplasia and achondrogenesis type IV.

[Thanatophoric dwarfism]. / Thanatophorer Zwergwuchs.

The thanatophoric dwarfism is a relatively rare disease. The course of a pregnancy with this in every case lethal syndrome is demonstrated in one case. The possible ultrasonographic suspected diagnosis is discussed. If the diagnosis is certain termination of pregnancy is indicated.