Gastric outlet obstruction and epidermolysis bullosa

Gastric outlet obstruction and epidermolysis bullosa Daniel W. Shaw, MD, a Jo-David Fine, MD, h Daniel J. Piacquadio, MD, a Mark J. Greenberg, MD, c Jessica Wang-Rodriguez, MD, d and Lawrence F. Eichenfield, i~/ID a San Diego, California, and Chapel Hill North Carolina

We describe a case of pyloric atresia coexisting with epidermolysis bullosa, almost certainly of the junctional type. The coexistence of pyloric atresia and junctional epidermolysis bullosa (PA-JEB syndrome) has been repeatedly observed. This syndrome has several clinical fea- tures that distinguish it from Herlitz junctional epidermolysis bullosa (JEB). These include a lack of prominent granulation tissue formation and increased frequencies of genitourinary tract involvement and ear anomalies. Aplasia curls congenita is sometimes present; esoph- ageal atresia is uncommonly present. In all 12 patients examined to date, normal basement membrane zone expression of laminin-5 biochemically distinguishes PA-JEB syndrome from Herlitz JEB. Mutations in the [34 integrin gene have been observed in one patient with PA- JEB syndrome. Thus there are both clinical and biochemical reasons to separate the PA-JEB syndrome from Herlitz JEB. This is the second known case of papillary hyperplasia of the amnion to be seen in any setting. The other was a case of JEB without pyloric atresia. (J Am Acad Dermatol 1997;36:304-10.)

Epidermolysis bullosa (EB) is divided into three major categories. 1 In EB simplex, blistering occurs within the epidermis, usually within the basal cell layer. In junctional EB (JEB), blistering occurs within the lamina lucida of the basement membrane zone and is often associated with reduced numbers or hypoplasia of hemidesmosomes. In dystrophic EB, blistering occurs beneath the lamina densa of the basement membrane zone.

Including this report, at least 73 cases of EB with congenital gastric outlet obstruction have been re- ported (Table I). Seventy-two of these were atresias (70 pyloric 2-44 and two duodenal.) 45' 46 Pyloric and

proximal duodenal atresias may be difficult to distinguish, which prompts some to refer to py- loroduodenal atresia. 47 Another case involved py-

ORTHO This article is made possible through an educational grant from the Dermatological Division, Ortho Pharmaceutical Corporation. There were no funding sources supporting this work.

From the Department of Medicine, Division of Dermatology) the De- partment of PediaUics, c and the Department of Pathology, d Univer- sity of California, San Diego and from the Department of Derma- tology, University of North Carolina at Chapel Hill and the National Epidermolysis Bullosa Registry. b

Reprint requests: Daniel W. Shaw, MD, UCSD Medical Center, Divi- sion of Dermatology (8420), 200 W. Arbor Dr., San Diego, CA 92103-84-20.

Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97 $5.00 + 0 16/4n7227

304

loroduodenal prolapse into the stomach without atresia. 5 There is also one case of acquired, sponta- neously resolving pyloric obstruction of uncertain cause. 48 Because pyloric atresia (PA) represents fewer than 1% of gastrointestinal atresias 49 and yet is by far the most common gastrointestinal atresia

reported in EB, the association is more than by chance alone.

CASE REPORT

A Mexican-American boy was born at 28 weeks' ges- tational age and weighed 940 gm; the pregnancy was complicated by polyhydramnios. Immediately after birth approximately 30% of the total body surface was eroded, including the posterior and lateral parts of the scalp and neck, the circumoral region, the flanks, groin, scrotum, lower part of the back, and the distal two thirds of both arms and legs. Some of the congenital erosions were sharply demarcated with a smooth glistening surface and contained prominent blood vessels (Figs. 1 and 2). The epidermis peeled off with minimal trauma. The ears were markedly hypoplastic and bound to the skull (Fig. 2). One ear lacked a patent external auditory canal. Nails and hair were normal.

The patient had infant respiratory distress syndrome and was treated with surfactant and mechanical ventila- tion. Gastric outlet obstruction was diagnosed by x-ray examination. Renal ultrasonography revealed bilateral hydronephrosis and hydroureter. The infant also had ane- mia, thrombocytopenia, and sepsis. After 16 days, life support was terminated and the infant died.

Journal of the American Academy of Dermatology Volume 36, Number 2, Part 2 S h a w et al. 305

Fig. 1. The distal two-thirds of the legs demonstrate smooth glistening surface, extremely prominent blood vessels, and sharp demarcation from normal skin.

Fig. 2. Both ears are markedly hypoplastic. Surround- hag skin demonstrates smooth glistening surface and ex- tremely enlarged blood vessels.

Uninvolved skin showed microscopic dermal-epider- mal vesiculation, normal dermal adnexae, and rare mildly engorged blood vessels. In contrast, congenitally involved erosions showed absent epidermis, rudimentary adnexae, and frequent massively engorged vessels (Fig. 3). Be- cause of problems with orientation of the specimen, elec- tron microscopy did not determine the level of basement membrane zone separation. Neither hemidesmosomal nor keratin abnormalities were observed.

Type IV collagen, laminin-1, laminin-5 (identified by GB3 antibody), and type VII collagen (identified by LH 7:2 antibody) were present in normal quantifies at the base of the microvesicle. Bnllous pemphigoid antigen was weakly expressed in intact skin, but not within the cleft. There was very weak and focal expression of uncein (19- DE J-1 antigen). There was complete absence of immu- noreactivity with use of an antibody directed against the [34 subunit of ot6134 integrin. This antibody intensely stained the dermal-epidermal junction of concurrently studied normal human skin.

An autopsy revealed a 2 cm longitudinal segment of pyloric and proximal duodenal atresia. Other gross feud-

hags included patent ductus arteriosus, massive gallblad- der distention, splenomegaly, bilateral hydronephrosis, and dilated ureters.

Microscopic findings included focal epithelial separa- tion in the trachea, bronchi, bronchioles, tongue, small and large intestines, renal pelvis, ureters, and bladder. Com- plete loss of epithelium was seen in the gallbladder and urethra, but this may have been secondary to autolysis. The pylorus showed a completely obliterated lumen with- out glands or mucosal lining. The duodenal smooth mus- cle was arranged in a haphazard fashion. The amniotic epi- thelium was partially eroded. It contained bulbous papil- lary projections of underlying stroma with increased num- bers of macrophages containing yellow pigment (Fig. 4).

DISCUSSION

In our patient's skin, a cleavage plane was not de- tected by electron microscopy. However, cleft for- marion within or above the lamina lucida was doc- umented by immunofluorescence antigenic map- ping, narrowing the diagnosis to JEB or EB simplex.

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Fig. 4. Amnion. Epithelium partially eroded. There are many bulbous projections of underlying stroma contain- ing an increased number of macrophages that contain yellow pigment.

Fig. 3. Congenitally involved skin of distal leg, post- mortem. Epidermis is absent. In marked contrast to unin- volved skin, all dermal adnexae are rudimentary. Numer- ous greatly enlarged blood vessels engorged with eryth- rocytes are present.

The expression of uncein along the dermal-epider- mal junction is nearly or completely absent in gen- eralized JEB, in contrast to its normal expression in EB simplex. 1 Therefore, this patient's nearly com- plete absence of uncein indicates that he almost cer- tainly had JEB.

On the basis of data from the U.S. National Epi- dermolysis BuUosa Registry 5° and from a recent re- view, 4 it is clear that PA, when it coexists with EB, is associated almost exclusively with JEB (PA-JEB syndrome). Various explanations for this association have been offered. 4,9, 11, 15-17

Pyloroduodenal atresias are classified into three major types51-54: type I (mucosal membrane occlud- ing the lumen), type II (longitudinal segmental atre- sia), and type III (gap aplasia). Whereas type I atre- sia predominates in non-EB cases, type II atresia predominates in PA-JEB syndrome (Table II).

This syndrome has several features in common with other generalized forms of JEB, including the Herlitz (letalis) type. These include an autosomal recessive inheritance, the usual occurrence of wide- spread trauma-induced erosions and bullae, the oc- casional presence of erosions of various internal ep- ithelia, and a high infant mortality rate (Table HI). For example, of 70 reported cases of PA-JEB, the PA was surgically corrected in 45. Of these, eight patients survived more than 1 year. 19-22'34 These patients had relatively mild cutaneous involvement.

Another feature reported in our patient and in one Herlitz JEB patient without PA 55 is papillary hyper- plasia of the amnion. This finding has, to our knowledge, never been described in any other setting. However, in the Herlitz JEB case, papillary projections contained two to three layers of overlap- ping cells in contrast to the diminished epithelium seen in our patient.

A number of features distinguish the PA- JEB syndrome from Herlitz JEB (Table 111). For example, epithelial separation in the genitourinary tract is found in 27% of patients with PA- JEB 6, 8, 13, 14, 19-24, 26, 34 (Table I) but is uncommon in Herlitz JEB, 56 occurring in only one 57 of 50 cases that we reviewed. The respiratory tract and the intestines may also be involved.

A typical feature of Herlitz JEB is the propensity to develop exuberant granulation tissue at sites of erosions.1 In contrast, this fmding is not mentioned in any of the patients with gastric outlet obstruction.

Polyhydramnios and premamrity are found in most patients with PA-JEB, probably secondary to

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Vo lume 36, N u m b e r 2, Part 2 Shaw et al. 307

Table I. Distribution of anomalies by type of congenital gastric outlet obstruction

I Total Genitourinary Aplasia cutis Ear Muscnioskeletal cases system congenita anomalies anomalies

Esophageal atresia

Pyloric atresia 244 Type I* (Membranous) 11 2 0 0 0 0 Type II? (Segmental) 35 10 7 8 4 15 Type 1II (Gap) 3°, 35 2 0 1 0 0 1 § Unknown typel I 22 7 3 2 2 1 §

Total 70 19 (27%) 11 (16%) 10 (14%) 6 (9%) 3 (4%) Duodenal atresia 45, 46

Unknown type 2 1 2 1 1 0 Pyloroduodenal prolapse 5 1 0 1 1 1 0

Grand total 73 20 (27%) 14 (19%) 12 (16%) 8 (11%) 3 (4%)

Note: Cases where gastrojejunostomy was performed were classified as type II, even if details of the atresia were lacking. 7, 8.10. 38 *Refs. 3, 4, 6, 12, 18, 37, 40, 41. tRefs. 2, 3, 5, 7-11, 13-17, 22, 28, 29, 31, 32, 34, 36, 38, 42-44, this case. :~Also had anal atresia. 43 §Atypical families. 27, 30 IIRefs. 9, 19-27, 33, 34, 39.

the pyloric obstruction. 58 Furthermore, in 37 re- ported cases with sufficient information, we calcu- lated 59 the birth weight to be at the 30th percentile, on average, for gestational age. Neither polyhydram- nios nor small size for gestational age are common features of Herlitz JEB without PA (Table ffl).

In patients who have EB with gastric outlet obstruction, 15% to 20% are described as having aplasia curls congenita or "skin defects." E a r 5, 8, 17, 23, 27, 28, 31-33, 45 and musculoskele- t a l 5, 8, 17, 27, 28, 31-33, 45 anomalies a r e m o s t often s e e n

in these patients, 6° but have not been observed in type I atresias (Table I). Ear anomalies have not, to our knowledge, been reported in Herlitz JEB with- out gastric outlet obstruction.

Coexisting esophageal atresia has been observed in three patients with PA-JEB,27, 30, 43 one of whom also had anal atresia. 43 In contrast, we could fmd no other EB patient with anal atresia and only one with esophageal atresia. 61

Expression of larninin-5 is absent or markedly re- duced in Herlitz JEB. 62 This protein is also known a s n i c e i n o r k a l i n i n , 63'64 i s identified by GB3 antibody, and is a protein constituent of normal an- choring fdaments in the lamina lucida. Laminin-5 gene defects have been identified in Herlitz JEB pa- r l e n t s . 65-67 Ill contrast, all 12 studied cases, including ours ,4 , 9, 25, 34-36, 68, 69 o f PA-JEB syndrome have

expressed normal quantities of laminin-5. In PA-JEB syndrome, expression of the [34 sub-

unit of or6 [34 integrin has been absent or altered in

Table II. Types of pyloric atresia

PA without EB* EB-associated

Type I (Membranous) 74 (67%) 11 (16%) Type II (Segmental) 28 (25%) 35 (50%) Type flI (Gap) 9 (8%) 2 (3%) Unknown type 22 (31%)

Total 111 70

*Kodama et a152 reported 131 cases of PA, but did not specify which had EB. By examination of the reference list, we determined that twenty cases of EB were included. These were subtracted from their data to yield the above numbers.

all five patients examined, including ours, 25, 34, 68, 69 whereas in Herlitz JEB it has been normal 68' 70 or altered.69, 71 In addition, mutations in [34 integrin gene alleles have been observed in one patient with PA-JEB 25 but have not been studied in Herlitz JEB. This integrin is a constituent of the basal cell hemidesmosomes, structures important for dermal- epidermal adhesion. 25

In summary, gastric outlet obstruction associated with JEB is a syndrome distinct from Herlitz JEB. PA is the most common type. The PA-JEB syn- drome has an increased frequency of genitourinary system involvement and ear anomalies and an apparent lack of prominent granulation tissue for- marion. Its pathogenesis is distinct; expression of laminin-5 is normal, in contrast to Herlitz JEB. Fi- nally, mutations of the [34 integrin gene appear to cause some cases of PA-JEB syndrome.

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T a b l e I I I . C o m p a r i s o n be tween P A - J E B s y n d r o m e and Herl i tz JEB

Herlitz JEB (without PA) PA-JEB syndrome

Similarities Autosomal recessive inheritance Widespread bullae/erosions High infant mortality Papillary hyperplasia of amnion* Absence (or marked decrease) of uncein

Differences Exuberant granulation tissue Genitourinary tract involved Ear anomalies Aplasia cutis congenita Musculoskeletal anomalies Esophageal atresia Anal atresia Prematurity Polyhydramnios Small for gestational age Laminin-5 expression Laminin-5 gene mutations a6 [34 integrin expression a6 [34 integrin gene mutations

Yes Yes Typical Typical Yes Yes Reported once Reported once Yes Yes

Frequent Absent Rare - 2 5 % to 30% Not reported - 15% Uncommon - 1 5 % to 20% Uncommon - 10% Not reported - 5 % Not reported One caset Uncommon Very common Uncommon Very common Uncommon Very common Absent or reduced Normal Present None observed Normal or abnormal Abnormals Not studied Present§

*The amniotic findings in the two cases are not identical (see text). tCoexisting pyloric, esophageal, and anal atresias. 43 :~In five of five studies fiefs. 25, 34, 68, 69, this case). §Studied in only one patient. 25

Note added in proof: Four m o r e recent P A - J E B

cases have all demons t ra t ed no rma l laminin-5 and abnorma l a6134 integrin expression. 72,73 T w o o f

these demons t ra ted comple t e absence o f a 6 and marked ly reduced [34 integrin expression, 7e one an

absence o f bo th integrins, 73 and another an absence o f [34 integrin only. 73 This suggests a he te rogenei ty

in integrin pheno types m a y occur in this syndrome.

REFERENCES

1. Fine J-D, Bauer EA, Briggaman RA, et al. Revised clini- cal and laboratory criteria for subtypes of inherited epider- molysis bullosa: a consensus report by the Subcommittee on Diagnosis and Classification of the National Epider- molysis Bullosa Registry. J Am Acad Dermatol 1991;24: 119-35.

2. Defawe G, Le Marec B, Chevrant-Breton J, et al. Atr6sie du pylore et 6pidermolyse bulleuse: apropos d'un nouveau cas. Arch Fr Pediatr 1981;38:511-2.

3. Korber JS, Glasson MJ. Pyloric atresia associated with epidermolysis bullosa. J Pediatr 1977;90:600-1.

4. Lestringant GG, Akel SR, Qayed KI. The pyloric atresia- junctional epidermolysis bullosa syndrome: report of a case and review of the literature. Arch Dermatol 1992;128: 1083-6.

5. Cetin N, Patiroglu T. Epidermolysis bullosa associated with pyloric obstruction. Turk J Pediatr 1987;29:253-7.

6. Bull MJ, Norins AL, Weaver DD, et al. Epidermolysis

bullosa-pyloric atresia: an autosomal recessive syndrome. Arn J Dis Child 1983;137:449-51.

7. Egan N, Ward R, Olmstead PM, et al. Junctional epider- molysis bullosa and pyloric atresia in two siblings. Arch Dermatol 1985; 121:1186-8.

8. E1 Shafie M, Stidham GL, Klippel CH, et al. Pyloric atre- sia and epidermolysis bullosa letalis: a lethal combination in two premature newborn siblings. J Pediatr Surg 1979; 14: 446-9.

9. Nazzaro V, Nicolini U, De Luca L, et al. Prenatal diagno- sis of junctional epidermolysis bullosa associated with py- loric atresia. J Med Genet 1990;27:244-8.

10. Rosenbloom MS, Ratner M. Congenital pyloric atresia and epidermolysis bullosa letalis in premature siblings. J Pedi- atr Surg 1987;22:374-6.

11. De Groot WG, Postuma R, Hunter AGW. Familial pyloric atresia associated with epidermolysis bullosa. J Pediatr 1978;92:429-31.

12. Swinburne L, Kohler HG. Symmetrical congenital skin defects in sibs. Arch Dis Child 1968;43:499.

13. Dennery PA, Conover PT, Kahn T, et al. Premature twins with skin lesions and gastric outlet obstruction. J Pediatr 1992; 120:645-51.

14. Abramowsky CR, Gilbert-Barness E. Pathological cases of the month. Am J Dis Child 1993;147:207-8.

15. Weber M. Hemidesmosome deficiency of gastrointestinal mucosa, demonstrated in a child with Herfitz syndrome and pyloric atresia. Acta Derm Venereol (Stockh) 1987;67: 360-2.

16. Peltier FA, Tschen EH, Raimer SS, et al. Epidermolysis bullosa letalis associated with congenital pyloric atresia. Arch Dermatol 1981;117:728-31.

Jotmlal of the American Academy of Dermatology Volume 36, Number 2, Part 2 Shaw et al. 309

17. Chang CH, Perrin EV. Pyloric atresia associated with epi- dermolysis bullosa: special reference to pathogenesis. Pe- diatr Pathol 1983;1:449-57.

18. Garcia Valles MC, Martinez Caro A, Hemandez Orgaz A. Atresia del piloro y epidermolisis ampollosa/,una coinci- dencia?. An Esp Pediatr 1977;10:745-50.

19. Berger TG, Detlefs RL, Donatucci CF. Junctional epider- molysis bullosa, pyloric atresia, and genitourinary disease. Pediatr Dermatol 1986;3:130-4.

20. EklSf O, Parkkulalnen K. Epidermolysis bullosa dystroph- ica with urinary tract involvement. J Pediatr Surg 1984; 19:215-7.

21. Rosenberg D, Dodat H, Cotfin X, et al. Atteinte du Iractus urinaire au cours du syndrome 6pidermolyse bulleuse cong6nitale-atr6sie du pylore. Arch Fr Pediatr 1987;44: 867-70.

22. Hayashi AH, Galliani CA, Gillis DA. Congenital pyloric atresia and junctional epidermolysis bullosa: a report of long-term survival and a review of the literature. J Pediatr Surg 1991;26:1341-5.

23. Dolan CR, Smith LT, Sybert VP. Prenatal detection of epidermolysis bullosa letalis with pyloric atresia in a fetus by abnormal ultrasound and elevated alpha-fetoprotein. Am J Med Genet 1993;47:395-400.

24. Miiller H, Bode H, Krone C, et al. Herlitz-syndrom und "pylomsatresie". Helv Paediatr Acta 1988;43:457-66.

25. Vidal F, Aberdam D, Miquel C, et al. Integrin 134 mutations associated with junctional epidermolysis bullosa with py- loric atresia. Nat Genet 1995;10:229-34.

26. Reitelman C, Burbige KA, Mitchell ME, et al. The urolog- ical manifestations of epidermolysis bullosa. J Urol 1986; 136:1320-2.

27. Carmi R, Sofer S, Karplus M, et al. Aplasia cuffs congen- ita in two sibs discordant for pyloric atresia. Am J Med Genet 1982;11:319-28.

28. Cowton JAL, Beattie TJ, Gibson AAM, et al. Epidermol- ysis bullosa in association with aplasia cuffs congenita and pyloric atresia. Acta Paediatr Scand 1982;71:155-60.

29. Nair PM, Chellam VG, Sabarinathan K. Epidermolysis bullosa-pyloric atresia syndrome. Indian J Pediatr 1989;56: 283-6.

30. Vivona G, Fmntali M, Di Nunzio ML, et al. Aplasia cuffs congeuita and/or epidermolysis bullosa. Am J Med Genet 1987;26:497-502.

31. Adashi EY, Louis FJ, Vasquez M. An unusual case of epi- dermolysis bullosa hereditaria letalis with cutaneous scar- fing and pyloric atresia. J Pediatr 1980;96:443-6.

32. Marras A. Epidermolysis bullosa and amniotic bands. Am J Med Genet 1984;19:815-7.

33. Achiron R, Hamiel-Pinchas O, Engelberg S, et al. Aplasia cuffs congenita associated with epidermolysis bullosa and pyloric atresia: the diagnostic role of prenatal ultrasonog- raphy. Prenat Diagn 1992;12:765-71.

34. Valari MD, Phillips R J, Lake BD, et al. Junctional epider- molysis bullosa and pyloric atresia: a distinct entity. Clin- ical and pathological studies in five patients. Br J Dermatol 1995;133:732-36.

35. Lacour JP, Hoffman P, Bastiani-Griffet F, et al. Lethal junctional epidermolysis bullosa with normal expression of BM 600 and antro-pyloric atresia: a new variant of junc- tional epidermolysis bullosa? Eur J Pediatr 1992; 151:252-7.

36. Shimizu H, Fine J-D, Suzumori K, et al. Prenatal exclusion of pyloric atresia-junctional epidermolysis bullosa syn- drome. J Am Acad Dermatol 1994;31:429-33.

37. Ishigami T, Akaishi K, Nishirnura S, et al. A case of py- loric atresia associated with junctional epidermolysis bullosa. Eur J Pedriatr 1990;149:306-7.

38. Nazir Z, Attar ZB, Moazam F. Congenital pyloric atresia and epidermolysis bullosa. JPMA J Pak Med Assoc 1991 ;41:25-6.

39. Orense M, Garcia Hemandez JB, Celorio C, et al. Pyloric atresia associated with epidermolysis buUosa. Pediatr Ra- diol 1987;17:435.

40. Pedersen PV. Pyloric atresia and epidermolysis bullosa. J Pediatr 1977;91:852-3.

41. Roman Ortiz ME, Gutierrez Sanchez JD, Rodriguez Caa- mafio J, et al. Sfndrome de atlesia pil6rica-epidermolisis bullosa cong6uita: descripci6n de un nuevo caso. An Esp Pediatr 1991;35:419-21.

42. Meldgaard Lund A, Karlsmark T, Kobayasi T. Protein- losing entempathy in a child with junctional epidermolysis bullosa and pyloric atresia. Acta Derm Venereol 1995;75:59-61.

43. ~etinkursun S, 0zttirk H, Celasun B, et al. Epidermolysis bullosa associated with pyloric, esophageal, and anal atle- sia: a case report. J Pediatr Surg 1995;30:1477-8.

44. Ng CC, Hung FC, Hsieh CS, et al. Epidermolysis bullosa letalis with pyloric atresia in an infant. J Formos Med As- soc 1996;95:61-5.

45. Leschot NJ, Treffers PE, Becker-Bloemkolk MJ, et al. Se- vern congenital skin defects in a newborn. Eur J Obstet Gynecol Reprod Biol 1980;10:381-8.

46. Zim JR, Scott RA, Aronian JM, et al. Gastric outlet obstruction and gastric infarct in junctional epidermolysis bullosa. Pediatr Dermatol 1995;12:174-7.

47. Melhem RE, Salem G, Mishalany H, et al. Pyloro-duode- nal atresia: a report of three families with several similarly affected children. Pediatr Radiol 1975;3:1-5.

48. Honig PJ, Yoder M, Ziegler M. Acquired pyloric obstruc- tion in a patient with epidermolysis hnllosa letalis. J Pedi- atr 1983;102:598-600.

49. Thompson NW, Parker W, Schwartz S, et al. Congenital pyloric atresia. Arch Surg 1968;97:792-6.

50. Fine J-D, Johnson LB, Tien H, et al. The national epider- molysis bullosa (EB) registry--differences in frequencies of selected gastrointestinal manifestations and cancers across major disease types. J Invest Dermatol 1994;102: 618.

51. Moore CM. Congenital gastric outlet obstluction. J Pediatr Surg 1989;24:1241-6.

52. Kodama Y, Kawamoto M, Iwashita K, et al. Congenital pyloric atresia--a repolt on a successfully treated case and existing research. J Nippon Med Sch 1986;53:409-15.

53. Miiller M, Morger R, Engert J. Pyloric atresia: report of four cases and review of the literature. Pediatr Surg hat 1990;5:276-9.

54. Rowe MI, O'Neill JA, Grosfeld JL, et al. Essentials of pe- diatric surgery. St. Louis: Mosby, 1995:486,501-2.

55. Faulk WP, Hsi BL, Yeh CJG, et al. Epidermolysis bullosa letalis: an immunogenetic disease of extraembryouic ecto- derm? Am J Obstet Gynecol 1988;158:150-7.

56. Donatucci CF, Berger TG, Deshon GE. Management of urinary tract in children with epidermolysis bullosa. Urol- ogy 1992;40:137-42.

57. Schachner L, Lazarus GS, Dembitzer H. Epidermolysis bullosa hereditaria letalis--pathology, natural history and therapy. Br J Dermatol 1977;96:51-8.

58. Cardwell MS. Polyhydramnios: a review. Obstet Gynecol Surv 1987;42:612-7.

59. Lubchenco LO, Hansman C, Boyd E. Intrauterine growth in length and head circumference as estimated from live births at gestational ages from 26 to 42 weeks. Pediatrics 1966;37:403-8.

60. Frieden IJ. Aplasia cutis congenita: a clinical review and

3 1 0 S h a w et al. Journal of the American Academy of Dermatology

February 1997

proposal for classification. J Am Acad Dermatol 1986; 14: 646-60.

61. Doi O, Aoyama K, Mori S, et al. A case of epidermolysis bullosa dystrophicans with congenital esophageal atresia. J Pedialr Surg 1986;21:943-5.

62. Schofield OMV, Fine J-D, Verrando P, et al. GB3 mono- clonal antibody for the diagnosis of junctional epidermol- ysis bullosa: results of a multicenter study. J Am Acad Dermatol 1990;23:1078-83.

63. Burgeson RE, Chiquet M, Deutzmann R, et al. A new no- menclature for laminins. Matrix Biol 1994;14:209-11.

64. Marinkovich MP, Verrando P, Keene DR, et al. Basement membrane proteins kalinin and nicein are structurally and immunologically identical. Lab Invest 1993;69:295-9.

65. Pulkkinen L, Christiano AM, Airenne T, et al. Mutations in the "y2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa. Nat Genet 1994;6:293-7.

66. Pulkkinen L, Christiano AM, Gerecke D, et al. A homozy- gous nonsense mutation in the 133 chain gene of laminin 5 (LAMB3) in Herlitz junctional epidermolysis bullosa. Ge- nomics 1994;24:357-60.

67. Kivirikko S, McGrath JA, Baudoin C, et al. A homozygous nonsense mutation in the o~3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa. Hum Mol Genet 1995;4:959-62.

68. Gil SG, Brown TA, Ryan MC, et al. Junctional epidermol- ysis bullosis: defects in expression of epiligrin/nicein/kali- nin and integrin 134 that inhibit hemidesmosome formation. J Invest Dermatol 1994;103:31S-38S.

69. Phillips RJ, Aplin JD, Lake BD. Antigenic expression of integrin c~6134 in junctional epidermolysis bullosa. Histo- pathology 1994;24:571-6.

70. Fine J-D, Quaranta V, Horiguchi Y, et al. Relative expres- sion of four hemidesmosome-associated proteins in junc- tional epidermolysis bullosa, a disease of epithelial dysad- hesion with known abnormal hemidesmosomes. J Cell Biol 1991;115:134A.

71. Jonkman MF, de Jong MCJM, Heeres K, et al. Expression of integrin a6134 in junctional epidermolysis bullosa. J In- vest Dermatol 1992;99:489-96.

72. Shimizu H, Suzumori K, Hatta N, et al. Absence of detect- able a6 integrin in pyloric atresia-junctional epidermolysis bullosa syndrome: application for prenatal diagnosis in a family at risk for recurrence. Arch Dermatol 1996; 132:919- 25.

73. Brown TA, Gil SG, Sybert VP, et al. Defective integrin a6134 expression in the skin of patients with junctional epi- dermolysis bullosa and pyloric atresia. J Invest Dennatol 1996;107:384-91.