Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia

Schneider, Holm; Faschingbauer, Florian; Schuepbach‐Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk‐Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W.; Schneider, Pascal

doi:10.1056/nejmoa1714322

Cited by 116 publications

(73 citation statements)

References 20 publications

(2 reference statements)

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“…The same experiment was repeated in EDA mutant dogs, and their severe oligodontia was almost completely prevented . These results have prompted scientists to start clinical trials in humans to rescue the HED phenotype and, interestingly, promising results were reported recently from one trial . EDA research is an excellent demonstration that the results of basic biology research may be applied in the future for the prevention of congenital malformations.…”

Section: The Causes and Possible Prevention Of Hypodontia In Humansmentioning

confidence: 94%

From understanding tooth development to bioengineering of teeth

Thesleff

2018

European J Oral Sciences

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Remarkable breakthroughs in the fields of developmental biology and stem cell biology during the last 15 yr have led to a new level of understanding regarding how teeth develop and how stem cells can be programmed. As a result, the possibilities of growing new teeth and of tooth bioengineering have been explored. Currently, a great deal is known about how signaling molecules and genes regulate tooth development, and modern research using transgenic mouse models has demonstrated that it is possible to induce the formation of new teeth by tinkering with the signaling networks that govern early tooth development. A breakthrough in stem cell biology in 2006 opened up the possibility that a patient's own cells can be programmed to develop into pluripotent stem cells and used for building new tissues and organs. At present, active research in numerous laboratories around the world addresses the question of how to program the stem and progenitor cells to develop into tooth-specific cell types. Taken together, the remarkable progress in developmental and stem cell biology is now feeding hopes of growing new teeth in the dental clinic in the not-too-distant future.

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Section: The Causes and Possible Prevention Of Hypodontia In Humansmentioning

confidence: 94%

From understanding tooth development to bioengineering of teeth

Thesleff

2018

European J Oral Sciences

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“…Early detection is important for individual symptom management and to potentially prevent morbidity and mortality associated with hypohidrosis. Additionally, early diagnosis may be important for family planning counseling, particularly in light of clinical trials working toward successful treatment of XLHED in‐utero (Schneider et al, ). Finally, a more complete understanding of the spectrum of XLHED characteristics may help clinicians counsel families about the natural history of XLHED, including variability of phenotypes.…”

Section: Introductionmentioning

confidence: 99%

The characterization of hypodontia, hypohidrosis, and hypotrichosis associated with X‐linked hypohidrotic ectodermal dysplasia: A systematic review

Anbouba

Carmany

Natoli

2020

American J of Med Genetics Pt A

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The objective of this study was to review the published literature on X‐linked hypohidrotic ectodermal dysplasia (XLHED) for the prevalence and characteristics of three features of XLHED: hypodontia, hypohidrosis, and hypotrichosis. A systematic search of English‐language articles was conducted in May 2019 to identify publications with information on any of the three features of XLHED. We excluded studies with five or fewer participants, that did not specify X‐linked inheritance or an EDA mutation, and discussed only management of features. The weighted means for total missing teeth, location of missing teeth, prevalence of reduced and absent sweating ability, and sparse or absent hair were analyzed across all studies. Additional findings for hypodontia, hypohidrosis, and hypotrichosis were summarized qualitatively. Twenty publications (18 studies) were accepted. Reported findings for males tended to be more informative than for carrier females. The weighted mean for missing teeth for affected males was 22.4 (range: 10–28) and carrier females was 3.4 (range: 0–22). The most common conserved teeth for males were the canines. The most common missing teeth for females were the maxillary lateral incisors. The weighted mean prevalence of reduced or absent sweating ability was 95.7% for males and 71.6% for females. The weighted mean prevalence for hypotrichosis was 88.1% for males and 61.6% for females. This systematic review provides insight into the prevalence, characteristics, and variability of the three classic features of XLHED. These findings provide detailed natural history information for families with XLHED as well as key characteristics that can aid in diagnosis.

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“…New therapeutic options may arise from a recombinant EDA1 molecule, which rescued normal development in murine and canine models of XLHED . In order to achieve the same therapeutic effects in humans, prenatal administration of the EDA1 replacement protein appears to be required . Three recent case studies have shown that intraamniotic injection of recombinant EDA1 at the beginning of the third trimester of pregnancy may prevent the development of XLHED‐related morbidity .…”

Section: Introductionmentioning

confidence: 99%

“…In order to achieve the same therapeutic effects in humans, prenatal administration of the EDA1 replacement protein appears to be required . Three recent case studies have shown that intraamniotic injection of recombinant EDA1 at the beginning of the third trimester of pregnancy may prevent the development of XLHED‐related morbidity . A clinical trial to evaluate this therapeutic approach is currently being prepared.…”

Section: Introductionmentioning

confidence: 99%

Reliability of prenatal detection of X‐linked hypohidrotic ectodermal dysplasia by tooth germ sonography

et al. 2018

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Objective In X‐linked hypohidrotic ectodermal dysplasia (XLHED), dysfunction of ectodysplasin A1 (EDA1) due to EDA mutations results in malformation of hair, teeth, and sweat glands. Hypohidrosis, which can cause life‐threatening hyperthermia, is amenable to intrauterine therapy with recombinant EDA1. This study aimed at evaluating tooth germ sonography as a noninvasive means to identify affected fetuses in pregnant carrier women. Methods Sonography, performed at 10 study sites between gestational weeks 18 and 28, led to the diagnosis of XLHED if fewer than six tooth germs were detected in mandible or maxilla. The assessment was verified postnatally by EDA sequencing and/or clinical findings. Estimated fetal weights and postnatal weight gain of boys with XLHED were assessed using appropriate growth charts. Results In 19 of 38 sonographic examinations (23 male and 13 female fetuses), XLHED was detected prenatally. The prenatal diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counts obtained by clinical examination corresponded well with findings on panoramic radiographs. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. Conclusion Tooth germ sonography is highly specific and reliable in detecting XLHED prenatally.

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Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia

Cited by 116 publications

References 20 publications

From understanding tooth development to bioengineering of teeth

From understanding tooth development to bioengineering of teeth

The characterization of hypodontia, hypohidrosis, and hypotrichosis associated with X‐linked hypohidrotic ectodermal dysplasia: A systematic review

Reliability of prenatal detection of X‐linked hypohidrotic ectodermal dysplasia by tooth germ sonography

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