In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions.

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.

Junctional epidermolysis bullosa (JEB) is a group of recessively inherited genodermatoses, characterized by tissue separation in the epidermal basement membrane due to defective anchoring proteins. The lethal Herlitz type of this disorder is caused by absence of laminin-332. Affected individuals suffer from widespread erosions of skin and mucous membranes and very often die within the first year of life. Mouse models lacking the α3-or γ2-chain of laminin-332 have been developed and a spontaneous ß3-knockout mouse exists, but all die shortly after birth. We generated a new mouse model of JEB by knockin of the point mutation 628G>A (p.E210K) in the gene encoding the laminin-332 ß3-chain, LAMB3. In compound heterozygous humans, this mutation has always been associated with lifelong skin blistering without reduced life expectancy.Fourteen homozygous LAMB3 628G>A knockin mice were analyzed. Most of them showed skin blistering with tissue separation in the basement membrane soon after birth. Laminin-332 was almost completely absent. None of the homozygous LAMB3 628G>A knockin mice survived longer than 72 hours. LAMB3 gene expression levels in heterozygous and homozygous LAMB3 628G>A knockin mice, however, were similar to wild-type mice. Analysis of the LAMB3 transcript revealed alternative splicing in homozygous LAMB3 628G>A knockin mice: a 64 base-pair deletion of exon 7 led to a frame-shift and a premature termination codon. Due to alternative splicing, the phenotype of this new mouse model resembles that of knockout mice. The LAMB3 628G>A knockin mouse may contribute to a better understanding of the molecular basis of JEB.

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