Warfarin embryopathy: fetal manifestations

Wainwright, Helen; Beighton, Peter

doi:10.1007/s00428-010-0982-9

Cited by 25 publications

(16 citation statements)

References 15 publications

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“…The most consistent fetal anomalies described are nasal hypoplasia, depressed nasal bridge, stippling of uncalcified epiphyses (most frequently affecting the axial skeleton, proximal femur and calcaneus), mild hypoplasia of the nails and shortened fingers. Franco et al 12 suggested that warfarin may inhibit arylsulfatase enzyme activity, the cause of X-linked recessive chondrodysplasia punctata which is phenotypically similar to warfarin embryopathy 4. Although warfarin seems to be the safest anticoagulation for pregnant women with mechanical heart valves, this treatment is associated with the risk of congenital malformations in the newborn.…”

Section: Discussionmentioning

confidence: 99%

Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Barreira

Santos

2018

BMJ Case Reports

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Fetuses exposed to warfarin during pregnancy are at an increased risk of developing an embryopathy known as fetal warfarin syndrome or warfarin embryopathy. The most consistent anomalies are nasal hypoplasia and stippling of vertebrae or bony epiphyses. Management of pregnant patients on anticoagulation is challenging. Current guidelines suggest the use of warfarin if the therapeutic dose is ≤5 mg/day. We report the case of a newborn with signs of warfarin embryopathy born from a mother anticoagulated with warfarin due to mechanical mitral and aortic heart valves. Warfarin was required at the dose of 5 mg/day and was withheld without medical advice between weeks 8 and 10 with no other anticoagulation. The newborn presented with skeletal abnormalities and a ventricular septal defect that have not required specific treatment during the first year of life. Low-dose warfarin is associated with a lower risk of warfarin-related fetopathy but the risk of embryopathy seems unchanged.

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Section: Discussionmentioning

confidence: 99%

Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Barreira

Santos

2018

BMJ Case Reports

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“…Most of the abnormalities seen in Keutel syndrome are also common in chondrodysplasia punctata and warfarin embryopathy (Franco et al., ; Munroe et al., ; Wainwright & Beighton, ). Although it is known that the inactivation of arylsulfatase E (ARSE) leads to chondrodysplasia punctata, the actual substrate and function of this enzyme are still unknown (Weaver et al., ).…”

Section: Midface Hypoplasia Caused By Abnormal Cartilage Calcificatiomentioning

confidence: 99%

“…Similar features are seen in warfarin embryopathy (Fryns, van Fleteren, Mattelaer, & van den Berghe, 1984;Munroe et al, 1999) Warfarin embryopathy -Seen in children born to mothers treated with warfarin, an anticoagulant. Developmental abnormalities are similar to chondrodysplasia punctata and Keutel syndrome (Starling, Sinha, Boyd, & Furck, 2012;Wainwright & Beighton, 2010) (Franco et al, 1995;Munroe et al, 1999;Wainwright & Beighton, 2010). Although it is known that the inactivation of arylsulfatase E (ARSE) leads to chondrodysplasia punctata, the actual substrate and function of this enzyme are still unknown (Weaver et al, 2014).…”

Section: Keutel Syndrome Autosomal Recessive; Mgpmentioning

confidence: 99%

Role of Matrix Gla protein in midface development: Recent advances

Marulanda

Murshed

2018

Oral Diseases

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Craniofacial development is a delicate process that involves complex interactions among cells of multiple developmental origins, their migration, proliferation, and differentiation. Tissue morphogenesis of the craniofacial skeleton depends on genetic and environmental factors, and on specific signaling pathways, which are still not well understood. Developmental defects of the midface caused by the absence, delays, or premature fusion of nasal and maxillary prominences vary in severity; leading to clefts, hypoplasias, and midline expansion. In the current review, we focus on the importance of the chondrocranium in craniofacial growth and how its impaired development leads to midface hypoplasia. More importantly, we reported how Matrix Gla protein (MGP), a potent inhibitor of extracellular matrix mineralization, facilitates midface development by preventing ectopic calcification of the nasal septum. In fact, MGP may act as a common link in multiple developmental pathologies all showing midface hypoplasia caused by abnormal cartilage calcification. This brief review discusses the gap in knowledge in the field, raises pertinent questions, which remain unanswered, and sheds light on the future research directions.

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“…3,12,13,16 Supporting these observations, offspring of pregnant women receiving warfarin showed shortening and flattening of the nose, epiphyseal stippling, and cerebral hemorrhage. 31 Warfarin inhibits the VKORC1 complex, which recycles vitamin K. Offspring of pregnant rats treated with warfarin showed calcification and disruption of hypertrophic chondrocytes in long-bone epiphyses. These studies indicate that early gestational warfarin exposure results in bone dysplasia, whereas later exposure affects coagulation factors.…”

Section: Etiologies For Bcp In Patients Without Arse Mutationsmentioning

confidence: 99%

A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies

Matos-Miranda

Nimmo

B³

et al. 2013

Genetics in Medicine

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Brachytelephalangic chondrodysplasia punctata (BCP) describes a group of heterogeneous conditions with overlapping phenotypes. X-linked recessive BCP (CDPX1) (OMIM no. 302950), originally recognized by Sheffield et al., 1 is a panethnic congenital rare disorder that affects males. The most characteristic clinical features are as follows: 2,3 (i) Chondrodysplasia punctata, or stippled epiphyses, observed on X-ray. These minimally involve the ankle and distal phalanges but can also include long bones, vertebrae, hips, costochondral junctions, hyoid bone, and tracheal and bronchial cartilage. Chondrodysplasia punctata can be observed initially in the second trimester of pregnancy by ultrasound but tends to improve or disappear by age 2-3 years. (ii) Brachytelephalangy, or shortening of the distal phalanges. A characteristic finding on X-ray is an inverted triangle appearance of the distal phalanges, with punctata on either side. (iii) Nasomaxillary hypoplasia, referring to absence or hypoplasia of the anterior nasal spine, causing a flat nasal base, reduced nasal tip protrusion, shortened columella, and vertical grooves within the alae nasi. (iv) Proportionate short stature. Another commonly observed characteristic is mixed conductive and sensorineural hearing loss. Most children have normal intellect and life span, but comorbidities can be present, including compression of the cervical spinal cord associated with cervical vertebral abnormalities or stenosis of the upper and lower airways that result from extensive calcifications within the tracheal and bronchial cartilage. 3,4 Intrafamilial differences in disease severity have also been documented. 3 The only known genetic cause of CDPX1 is defects in arylsulfatase E (ARSE). The ARSE gene is located at Xp22.3, within a cluster of contiguous arylsulfatase genes that share high sequence homology, escape X inactivation, and have pseudogenes on the Y chromosome. 5 There are 17 sulfatases in the human genome; all share extensive sequence homology and contain a highly conserved cysteine that undergoes a unique posttranslational modification essential for their catalytic activity. 6-8 ARSE is localized to the Golgi membranes, 9 and its transcript has been identified in multiple tissues. 5 Its protein product is a 589-amino-acid and 60 kD precursor, which is subject Purpose: The only known genetic cause of brachytelephalangic chondrodysplasia punctata is X-linked chondrodysplasia punctata 1 (CDPX1), which results from a deficiency of arylsulfatase E (ARSE). Historically, ARSE mutations have been identified in only 50% of male patients, and it was proposed that the remainder might represent phenocopies due to maternal-fetal vitamin K deficiency and maternal autoimmune diseases. Methods:To further evaluate causes of brachytelephalangic chondrodysplasia punctata, we established a Collaboration Education and Test Translation program for CDPX1 from 2008 to 2010. Of the 29 male probands identified, 17 had ARSE mutations that included 10 novel missense alleles and one single-cod...

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Warfarin embryopathy: fetal manifestations

Cited by 25 publications

References 15 publications

Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Low-dose warfarin maternal anticoagulation and fetal warfarin syndrome

Role of Matrix Gla protein in midface development: Recent advances

A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies

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