RESEARCH LETTER

The key role of ultrasound examination in the prenatal diagnosis ofepidermolysis bullosa with pyloric atresiaPaul Maurice1, Dominique Eyrolle-Guignot2, Ferdinand Dhombres1, Catherine Garel3, Marie Gonzales4, Françoise Muller5

and Jean-Marie Jouannic1*

1Service de Gynécologie-Obstétrique et Centre Pluridisciplinaire de Diagnostic Prénatal de l’ Est Parisien, Hôpital Armand Trousseau, APHP, Paris, France2Service de Gynécologie-Obstétrique, Centre Hospitalier, Papeete, France3Service de Radiopédiatrie, et Centre Pluridisciplinaire de Diagnostic Prénatal de l’ Est Parisien, Hôpital Armand Trousseau, APHP, Paris, France4Unité de foetopathologie et Centre Pluridisciplinaire de Diagnostic Prénatal de l’ Est Parisien, Hôpital Armand Trousseau, APHP, Paris, France5Service de Biochimie, Hôpital Robert Debré, APHP, Paris, France*Correspondence to: Jean-Marie Jouannic. E-mail: jean-marie.jouannic.aphp@trs.aphp.fr

Funding sources: NoneConflicts of interest: None declared

DNA-based prenatal diagnosis is now available for anincreasing number of genodermatoses.1 In de novo cases,direct prenatal ultrasound may lead to a strong suspicion inonly very few cases, mainly represented by the most severeform of congenital ichthyosis, that is, Harlequin ichthyosis.2

Thus, for others, including epidermolysis bullosa (EB) anddisorders of pigmentation, fetal skin lesions are not accessibleto prenatal ultrasound examination. Therefore, in EB, the onlyinstance for considering this diagnosis in the prenatal period,in the absence of familial cases, is based on the detection ofassociated anomalies. Pyloric atresia represents the mostcommonly associated feature, although others includingureteral stenosis, arthrogryposis, and nose or ear deformitieshave been reported.3 We report a case of EB with pyloricatresia, in a family not known to be at risk and for whichdetailed ultrasound examination has played a key role in theprenatal diagnosis.

The case of a 34-year-old primigravid Polynesian womanwas referred to us through telemedicine sharing after thediagnosis at routine 33weeks’ ultrasound examination ofpolyhydramnios (amniotic fluid index = 45 cm). Her husbandhad two healthy children from a previous marriage. Therewas no known familial disease. First-level ultrasoundexamination had revealed no fetal anomalies except for alarge stomach bubble. Amniocentesis had been performed.Fluorescence in situ hybridization examination was normal,but biochemical analysis of the amniotic fluid revealedextremely high level of alfa-fetoprotein (AFP) (30MoM). Atfirst glance, such levels of AFP in the amniotic fluid orientedour diagnostic approach to two main conditions associatedwith fetal AFP leakage of renal or cutaneous origin (as fetal

spine was normal and no abnormalities of the umbilicalcordon were observed).4 Complementary analysis of theamniotic fluid was requested consisting in electrophoresis ofacetylcholinesterase. An unusual pattern was found with thepresence of an abnormal additional slow band. Thesefindings strengthened our hypothesis of abrasivegenodermatosis. Confirmation of this diagnosis by fetal skinbiopsy as reported previously5 was considered, but maternaltransfer to our center in Paris or any other regional centerwas impossible because of a severe threat of premature labor.Thus, knowing the key role of ultrasound in the prenataldiagnosis of EB with pyloric atresia, we decided to ask ourlocal sonographer to search for ultrasound signs of pyloricatresia, as previously observed in another case in Paris.5 Ourcolleague was asked to provide us with additional views ofthe fetal stomach. The transmitted images revealed typicalappearance of a gastric outlet obstruction (Figure 1). Largeintra-gastric sediments, although not pathognomonic fromfetal abrasive skin lesion, were also observed. The parentswere informed of the high suspicion of EB with pyloric atresiaand opted for termination of the pregnancy that wasperformed at 35weeks in accordance with French legislation.The parents declined post-mortem examination but agreedwith skin biopsies. The external examination of the fetusconfirmed the presence of extensive desquamation of theepidermis (Figure 2). Immunohistological examination ofthe skin confirmed the diagnosis of junctional EB.

Our case illustrates that a certain prenatal diagnosis ofthis sub-type of EB, which may represent 15% of the casesof EB,7 is feasible when all biological and clinical patternsalready described by others are present,5,6 with no need

Prenatal Diagnosis 2013, 33, 908–909 © 2013 John Wiley & Sons, Ltd.

DOI: 10.1002/pd.4137

for systematic in utero skin biopsy. These cardinal signs arerepresented by (1) unexplained polyhydramnios with highAFP levels in the amniotic fluid (>20MoM), (2) the presenceof an unusual addition slow band on ACH electrophoresisand (3) the presence of a dilated stomach suggestive ofpyloric atresia. The fetal skin biopsy remains warrantedwhen one of these signs is missing, including then anabnormal pattern on ACH electrophoresis as previouslyreported.6

This is of importance for parental counseling of thissevere genodermatosis associated with rapid neonataldemise. Indeed, in many centers worldwide, both therealization of fetal skin biopsy and interpretation ofimmunohistological examination of the skin representimportant limitations to the final diagnosis. Among the veryfew cases reported, preterm delivery occurred beforehistological examination has been made. We consider thatin these cases, this diagnosis could have been anticipatedin the prenatal period with no need for histologicalconfirmation to allow precise parental counseling.

WHAT’S ALREADY KNOWN ABOUT THIS TOPIC?

• In de novo cases of genodermatoses, direct prenatal ultrasoundmay lead to a strong suspicion in only very few cases, mainlyrepresented by the most severe form of congenital ichthyosis. Forothers, including epidermolysis bullosa and disorders ofpigmentation, fetal skin lesions are not accessible to prenatalultrasound examination.

WHAT DOES THIS STUDY ADD?

• Certain prenatal diagnosis of de novo cases of epidermolysisbullosa is feasible when all biological and clinical patterns arepresent without the need for histological confirmation.

• These cardinal signs are represented by (1) unexplainedpolyhydramnios with high AFP levels in the amniotic fluid (>20MoM), (2) the presence of an unusual addition slow band onacetylcholinesterase electrophoresis and (3) the presence of adilated stomach suggestive of pyloric atresia.

REFERENCES1. Fassihi H, Eady RA, Mellerio JE, et al. Prenatal diagnosis for severe inherited

skin disorders: 25years’ experience. Br J Dermatol. 2006;154(1):106–13.2. Berg C, Geipel A, Kohl M, et al. Prenatal sonographic features of

Harlequin ichthyosis. Arch Gynecol Obstet. 2003;268(1):48–51.3. Achiron R, Hamiel-Pinchas O, Engelberg S, et al. Aplasia cutis congenital

associated with epidermolysis bullosa and pyloric atresia: the diagnosticrole of prenatal sonography. Prenat Diagn 1992;12:765–71.

4. Crandall B, Chua C. Risks for fetal abnormalities after very andmoderately elevated AF-AFPs. Prenat Diagn 1997;17:837–41.

5. Lépinard C, Descamps P, Meneguzzi G, et al. Prenatal diagnosisof pyloric atresia-junctional epidermolysis bullosa syndrome in afetus not known to be at risk. Prenat Diagn. 2000;20(1):70–5.

6. Azarian M, Dreux S, Vuillard E, et al. Prenatal diagnosis of inheritedepidermolysis bullosa in a patient with no family history: a case reportand literature review. Prenat Diagn 2006;26(1):57–9.

7. Bodemer C. MAGEC-Necker Team. Epidermolysis bullosa in France:management in the national reference center for Genodermatosis.Dermatol Clin 2010;28:401–3.

Figure 1 Axial view of the fetal abdomen at 34weeks’ gestationshowing the enlarged stomach with a typical appearance of gastricoutlet obstruction. Note the presence of echogenic particles within thegastric lumen (arrow)

Figure 2 Post-mortem external examination of the fetus showingextensive areas of denuded skin on both lateral sides of the headwith deformed external ear

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Prenatal Diagnosis 2013, 33, 908–909 © 2013 John Wiley & Sons, Ltd.