Antenatal diagnosis of lethal skeletal dysplasias

Abstract

Lethal skeletal dysplasias (LSD) are a heterogeneous group of rare but important genetic disorders characterized by abnormal growth and development of bone and cartilage. We describe the diagnosis and outcome of 29 cases of lethal skeletal dysplasias evaluated between January 1989 and December 1996 at the University of Maryland Medical Center and the Ultrasound Institute of Baltimore. Two cases presented at delivery with no prenatal care while the remaining 27 cases were identified by antenatal sonography. Final diagnoses included thanatophoric dysplasia (14), osteogenesis imperfecta, type II (6), achondrogenesis (2), short rib syndromes (3), campomelic syndrome (2), atelosteogenesis (1), and no evidence of a skeletal dysplasia (1). Twenty out of 27 pregnancies were terminated with an average at detection of 21.6 weeks. The other 7 pregnancies that went on to deliver had an average age at detection of 29.2 weeks. Fetal abnormalities in the terminated pregnancies were identified at a significantly earlier gestational age (P = 0.0016) than the pregnancies that continued. While the identification of LSD by sonography was excellent (26/27), only 13/27 (48%) were given an accurate specific antenatal diagnosis. In 8/14 (57%) cases with an inaccurate or nonspecific diagnosis there was a significant or crucial change in the genetic counseling. Thus, while antenatal sonography is an excellent method for discovering LSD, clinical examination, radiographs, and autopsy are mandatory for making a specific diagnosis.

Direct Oxidation of β‐Aryl Substituted Aldehydes to α,β‐Unsaturated Aldehydes Promoted by an o‐Anisidine–Pd(OAc)2 Co‐catalyst

“…Ultrasound is the primary imaging modality used for the initial diagnostic evaluation of an affected fetus. Table 4 summarizes the diagnostic accuracy of two‐dimensional ultrasound (2D‐US) for prenatal diagnosis of skeletal dysplasias7, 61–64. A precise diagnosis has been reported in 31–65% of cases.…”

Synthesis and Characterization of a Symmetric Bis(7‐hydroxyflavylium) Containing a Methyl Viologen Bridge

“…So far only a few studies have discussed false‐negative diagnoses of skeletal dysplasias. Tretter et al 17 and Parilla et al 19 report that they had no false negatives. We had two false‐negative diagnoses: one fetus with achondroplasia was wrongly diagnosed as ‘structurally normal fetus, suspect familial large head, IUGR affecting mainly extremities’ and one with Ellis‐van Creveld was diagnosed as ‘suspected genetic syndrome, short long bones’.…”

“…We described the accuracy of our prenatal diagnosis with regard to the final diagnosis, as previously reported14–16, as either ‘correct ultrasound diagnosis’ or ‘partially correct ultrasound diagnosis’. There are few reports with data on the diagnostic accuracy of prenatal diagnosis of skeletal dysplasias14–19 (Table 3), not all of which include numbers of false negatives and false positives. The accuracy of prenatal diagnosis seems to have improved in recent years.…”

“…For France and the UK, both with ultrasound screening programs, the reported percentages of diagnosis before 24 weeks are similar (62% and 71%14, 15). In the USA, where ultrasound screening is not universal, these percentages range from 37%4 to 58%16 or 62%17.…”

Metal ions‐ and pH‐induced conformational changes of acutolysin A from Agkistrodon acutus venom probed by fluorescent spectroscopy

“…In everyday practice, the diagnosis and prognosis still depend on the clinical, radiologic, and pathologic criteria (Superti‐Furga et al, 2007). Several previously published series have emphasized the diagnostic and prognostic implications of prenatal ultrasonography in fetal skeletal disorders (Donnenfeld and Mennuti, 1987; Escobar et al, 1990; Sharony et al, 1993; Rasmussen et al, 1996; Gaffney et al, 1998; Tretter et al, 1998; Doray et al, 2000; Parilla et al, 2003; Krakow et al, 2008; Witters et al, 2008). Our study focuses on the pathologist's perspective, who handles this group of disorders at perinatal autopsy.…”