The congenital warfarin syndrome

Zakzouk, M. S.

doi:10.1017/s0022215100099011

Cited by 40 publications

(17 citation statements)

References 11 publications

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“…2006). Moreover, nasal hypoplasia is common in cases of warfarin embryopathy (Zakzouk, 1986), resulting in reduced nasal projection. This condition is associated with a reduction in nasal septal size resulting from the ectopic ossification of the septal cartilage early in development (Howe & Webster, 1992; Howe et al.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in cases of holoprosencephaly, which affects the growth of midline craniofacial structures, individuals can exhibit nasal septal reduction or agenesis associated with a flattened nasal bridge (Fitz, 1983;Kjaer et al 2002;Ribeiro et al 2006). Moreover, nasal hypoplasia is common in cases of warfarin embryopathy (Zakzouk, 1986), resulting in reduced nasal projection. This condition is associated with a reduction in nasal septal size resulting from the ectopic ossification of the septal cartilage early in development (Howe & Webster, 1992;Howe et al 1997).…”

Section: Introductionmentioning

confidence: 99%

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Nasal septal and craniofacial form in European‐ and African‐derived populations

2012

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As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in longsnouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth. Nevertheless, the nasal septum follows a growth trajectory similar to the facial skeleton and, as such, its prolonged period of growth may influence other aspects of facial development. Using computed tomography scans of living human subjects (n = 70), the goal of the present study is to assess the morphological relationship between the nasal septum and facial skeleton in European-and African-derived populations, which have been shown to exhibit early developmental differences in the nasal septal-premaxillary complex. First we assessed whether there is population variation in the size of the nasal septum in European-and African-derived samples. This included an evaluation of septal deviation and the spatial constraints that influence variation in this condition. Next, we assessed the relationship between nasal septal size and craniofacial shape using multivariate regression techniques. Our results indicate that there is significant population variation in septal size and magnitude of septal deviation, both of which are greater in the European-derived sample. While septal deviation suggests a disjunction between the nasal septum and other components of the facial skeleton, we nevertheless found a significant relationship between the size of the nasal septum and craniofacial shape, which appears to largely be a response to the need to accommodate variation in nasal septal size.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nasal septal and craniofacial form in European‐ and African‐derived populations

2012

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“…CNS malformations are observed less consistently and appear to depend on the dosage, timing, and duration of maternal warfarin prophylaxis. These malformations include ventriculomegaly, hydrocephaly, agenesis of the corpus callosum, optic atrophy, congenital cataracts, and mild to severe mental retardation (24,25).…”

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confidence: 99%

Identification of two novel transmembrane γ-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues

Kulman

Harris

Xie

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

100

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The proline-rich ␥-carboxyglutamic acid (Gla) proteins (PRGPs) 1 and 2 are the founding members of a family of vitamin Kdependent single-pass integral membrane proteins characterized by an extracellular amino terminal domain of approximately 45 amino acids that is rich in Gla. The intracellular carboxyl terminal region of these two proteins contains one or two copies of the sequence PPXY, a motif present in a variety of proteins involved in such diverse cellular functions as signal transduction, cell cycle progression, and protein turnover. In this report, we describe the cloning of the cDNAs for two additional human transmembrane Gla proteins (TMG) of 20 -24 kDa named TMG3 and TMG4. These two proteins possess extracellular Gla domains with 13 or 9 potential Gla residues, respectively, followed by membrane-spanning hydrophobic regions and cytoplasmic carboxyl terminal regions that contain PPXY motifs. This emerging family of integral membrane Gla proteins includes prolinerich Gla protein (PRGP) 1, PRGP2, TMG3, and TMG4, all of which are characterized by broad and variable distribution in both fetal and adult tissues. Members of this family can be grouped into two subclasses on the basis of their gene organization and amino acid sequence. These observations suggest novel physiological functions for vitamin K beyond its known role in the biosynthesis of proteins involved in blood coagulation and bone development. The identification and characterization of these proteins may allow a more complete understanding of the teratogenic consequences of exposure in utero to vitamin K antagonists, such as warfarin-based anticoagulants.

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“…The most commonly reported malformations were nasal hypoplasia [1^7], chondrodysplasia punctata [2,4,5,8^10], cleft lip and=or palate [1,3,11], choanal stenosis [2,24], ¢nger and toe defects [7,11], ocular defects [1,4,12] and brain anomalies [1,2,4,6,11,12,21,25]. Nasal hypoplasia involves stunted growth of the septum, resulting in a depressed nasal bridge.…”

Section: Discussionmentioning

confidence: 99%

Warfarin Embryopathy

Chan

Gilbert‐Barness

Tiller

2003

Pediatric Pathology & Molecular Medicine

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A 34-year-old gravida 2 para 1 (1001) mother was on prophylactic anticoagulation therapy because of pulmonary emboli postabdominal surgery. The pregnancy was terminated at 25 weeks' gestation after ultrasound examination showed a mild hydrocephalus and a cardiac structural defect. Congenital abnormalities of the delivered fetus included nasal hypoplasia, earfold atresia, bilobled lungs, coarctation of the aorta, ventricular septal defect, gastrochisis, and radiographic skeletal stippling. The radiological and physical findings were consistent with warfarin embryopathy.

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The congenital warfarin syndrome

Cited by 40 publications

References 11 publications

Nasal septal and craniofacial form in European‐ and African‐derived populations

Nasal septal and craniofacial form in European‐ and African‐derived populations

Identification of two novel transmembrane γ-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues

Warfarin Embryopathy

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