Craniosynostosis Following Fetal Methotrexate Exposure

Zarella, Christopher; Albino, Frank P.; Oh, Albert K.; Wood, Benjamin C.; Oluigbo, Chima; Myseros, John S.; Magge, Suresh N.; Keating, Robert F.; Rogers, Gary F.

doi:10.1097/scs.0000000000002423

Cited by 11 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibited glutamyl to γ-carboxyglutamyl transition of vitamin K-dependent proteins such as osteocalcin and periostin (Hanumanthaiah et al, 2001;Fernandez et al, 2014) Craniofacial malformations of the nose and airways, eye/ear defects and cleft lip in humans when taken during the first trimester of gestation (Hou, 2004) 60 µM 4-96 hpf Shortened head structures, a dent in the anterior ethmoid plate, which also showed altered cell morphology and disorganized cell stacking Lee et al, 2013;Liu et al, 2020 Folic acid antagonist which inhibits DNA synthesis and cell proliferation by competitively inhibiting dihydrofolate reductase (Lee et al, 2012) Craniosynostosis and microcephaly and incomplete cleft palate in humans (Granzow et al, 2003;Zarella et al, 2016) Acetaminophen (Paracetamol) 2.5-13.4 mM 0-120/72-120 hpf Palatoquadral length, ceratohyal length and head size reduced Cedron et al, 2020 Activation cytochrome P450 and increased apoptosis (Cedron et al, 2020) No affected phenotypes reported Cyclosporin A (Immunmodulator)…”

Section: Pharmaceuticals and Teratogenesis In Zebrafish Larvaementioning

confidence: 99%

Zebrafish Models of Craniofacial Malformations: Interactions of Environmental Factors

Raterman

Metz

Wagener

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The zebrafish is an appealing model organism for investigating the genetic (G) and environmental (E) factors, as well as their interactions (GxE), which contribute to craniofacial malformations. Here, we review zebrafish studies on environmental factors involved in the etiology of craniofacial malformations in humans including maternal smoking, alcohol consumption, nutrition and drug use. As an example, we focus on the (cleft) palate, for which the zebrafish ethmoid plate is a good model. This review highlights the importance of investigating ExE interactions and discusses the variable effects of exposure to environmental factors on craniofacial development depending on dosage, exposure time and developmental stage. Zebrafish also promise to be a good tool to study novel craniofacial teratogens and toxin mixtures. Lastly, we discuss the handful of studies on gene–alcohol interactions using mutant sensitivity screens and reverse genetic techniques. We expect that studies addressing complex interactions (ExE and GxE) in craniofacial malformations will increase in the coming years. These are likely to uncover currently unknown mechanisms with implications for the prevention of craniofacial malformations. The zebrafish appears to be an excellent complementary model with high translational value to study these complex interactions.

show abstract

Section: Pharmaceuticals and Teratogenesis In Zebrafish Larvaementioning

confidence: 99%

Zebrafish Models of Craniofacial Malformations: Interactions of Environmental Factors

Raterman

Metz

Wagener

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…This group showed that the use of sertraline and citalopram was associated with an increased risk of CS in the fetus. Zarella et al 34 also reported a series of cases showing premature fusion of the cranial sutures after fetal methotrexate exposure. Furthermore, this study reports that children who received folic acid as part of their chronic treatment had seven times higher odds of developing CS, which contrasts to what has been reported in the literature throughout the years, in which folic acid has not been significantly associated with CS development.…”

Section: Discussionmentioning

confidence: 98%

Sickle Cell Disease Association with Premature Suture Fusion in Young Children

Manrique

Toro-Tobon

Bade

et al. 2022

Plastic and Reconstructive Surgery - Global Open

Self Cite

View full text Add to dashboard Cite

Background: Sickle cell disease (SCD) leads to the formation of an atypical hemoglobin tetramer with reduced capacity to carry oxygen. Although correlation between SCD and craniosynostosis (CS) has been mentioned, these are mostly small series or case reports. This article aimed to study any correlation between these entities in a large pediatric population. Methods: We retrospectively reviewed head CT scans of SCD patients from 0 to 8 years of age who required a CT for issues unrelated to their head shape between 2012 and 2020. We excluded patients with known history of CS or any CS-related syndrome, hydrocephalus, shunt placement, history of cranial surgery, or any reported cerebral or cranial shape abnormality. Results: Ninety-four CT scans were analyzed. The mean age at imaging was 4.48 ± 2.30 years. CS prevalence in this cohort was 19.1%. Analysis between independent variables and patients with +CS showed that SCD-associated vasculopathy, first-degree relatives with SCD, and the use of folic acid had a statistically significant association with CS development.Conclusions: Approximately 20% of pediatric patients with SCD developed CS. This association was higher in those patients who had a family history of SCD, used folic acid, and had SCD-associated vasculopathy. While the clinical impact of these findings needs more extensive study, centers that manage patients with SCD should be aware of the relatively high concordance of these diagnoses, vigilantly monitor head shape and growth parameters, and understand the potential risks associated with unidentified or untreated CS.

show abstract

“…Aside from the extremity abnormalities, previous groups have described genitourinary, skeletal, and cardiovascular abnormalities, as well as anomalies including cleft lip, craniosynostosis, and other craniofacial malformations. 5,13,15 Studies comparing the incidence of deformities after MTX exposure to those present in the general population have concluded that there is a disproportionately higher incidence of pulmonary atresia, craniosynostosis, and limb deficiencies in patients exposed in utero to MTX. 8 Our series focuses on extremity abnormalities associated with MTX embryopathy.…”

Section: Discussionmentioning

confidence: 99%

Extremity Findings of Methotrexate Embryopathy

Mantilla-Rivas

Brennan²,

Goldrich

et al. 2019

Hand (New York, N,Y.)

Self Cite

View full text Add to dashboard Cite

Background: Methotrexate (MTX) is widely used as an immunosuppressant, chemotherapeutic, and abortifacient agent. It is also a potent teratogen, and intentional or unintentional exposure during pregnancy is associated with heterogeneous birth anomalies. Methods: We retrospectively reviewed a cohort of patients who presented to our clinic with limb anomalies in the setting of MTX embryopathy. Results: In our case series, we describe 7 cases of patients who had limb anomalies with heterogeneous functionality, from severely debilitating to completely asymptomatic. Most of the upper extremity anomalies in our group were managed conservatively. Conclusions: Methotrexate embryopathy is a rare but clinically important entity with phenotypic and functional variability. This series underscores the need for proper counseling of patients and raises concern regarding using this medication for the purpose of abortion.

show abstract

Craniosynostosis Following Fetal Methotrexate Exposure

Cited by 11 publications

References 12 publications

Zebrafish Models of Craniofacial Malformations: Interactions of Environmental Factors

Zebrafish Models of Craniofacial Malformations: Interactions of Environmental Factors

Sickle Cell Disease Association with Premature Suture Fusion in Young Children

Extremity Findings of Methotrexate Embryopathy

Contact Info

Product

Resources

About