Johanna Hammersen1, Sigrun Wohlfart1, Tamme W Goecke2, Angela Köninger3, Holger Stepan4, Ralph Gallinat5, Susan Morris6, Katharina Bücher7, Angus Clarke6,8, Stephanie Wünsche1, Matthias W Beckmann1, Holm Schneider1, Florian Faschingbauer1. 1. Center for Ectodermal Dysplasias, University Hospital Erlangen, Erlangen, Germany. 2. Department of Gynecology and Obstetrics, RWTH Aachen, Aachen, Germany. 3. Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany. 4. Department of Obstetrics, University Hospital Leipzig, Leipzig, Germany. 5. Frauenärztliche Gemeinschaftspraxis Günzburg-Ichenhausen, Günzburg, Germany. 6. Cardiff and Vale University Health Board, University Hospital of Wales, Cardiff, UK. 7. Department of Conservative Dentistry and Periodontology, University Hospital, Ludwig-Maximilians University, Munich, Germany. 8. Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK.
Abstract
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.
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.