Volume 92 Number 3
B r i e f clinical and laboratory observations
similar to those in patients whose p r e t r a n s p l a n t a t i o n sera h a d cytotoxic antibodies. G r o w t h potential at the time of r e n a l t r a n s p l a n t a t i o n influences growth after t r a n s p l a n t a t i o n . 11 Since growth velocity is greatest d u r i n g the first year of life, one m i g h t expect a n i n f a n t who receives a k i d n e y t r a n s p l a n t a n d m a i n t a i n s good renal function to grow well. Despite doses of prednisone o f 35.7 m g / m ~ in the i m m e d i a t e posttransp l a n t period a n d 13.5 m g / m ~ at the present time, o u r patient has s h o w n n o r m a l growth velocity. It has b e e n previously stated that p r e d n i s o n e in excess of 10 m g / m ~ / day adversely affected n o r m a l growth in children with o t h e r disease states ~' 1:~ a n d in allograft r e c i p i e n t s ? ' O n the basis o f our experience, we believe it is w o r t h a t t e m p t i n g a renal t r a n s p l a n t in infants, since chronic dialysis rarely results in a d e q u a t e growth a n d develo pment. This therapy m a y offer the child the best opportunity to resume growth if renal f u n c t i o n is m a i n t a i n e d .
4.
5.
6.
7.
8.
9.
10.
REFERENCES
1. Fine RN, Korsch BM, Brennan LP, Edelbrock HH, Stiles QR, Riddell HI, Weitzman JJ, Mickelson JC, Tucker BL, and Grushkin CM: Renal transplantation in young children, Am J Surg 125:559, 1973. 2. Lawson RK, Talwalkar YB, Musgrave JE, Campbell RA, and Hodges CV: Renal transplantation in pediatric patients, J Urol 113:225, 1975. 3. DeShazo CV, Simmons RL, Bernstein DM, DeShazo MM, Willmert J, Kjellstrand CM, and Najarian JS: Results of renal transplantation in 100 children, Surgery 76:461, 1974.
Familial pyloric atresia associated with epidermolysis bullosa William G. D e Groot, M . D . , Ray Postuma, M . D . , * and Alasdair G. W. Hunter, M . D . ,
Winnipeg, Manitoba, Canada
P'r I~o R I C A'r R E S I A associated with epidermolysis bullo-
sa was first reported in 1976 by K o r b e r a n d Glasson I in
From the Departments of Pediatrics and Surgery, Health Sciences Children's Centre, and University of Manitoba. *Reprint address: Health Sciences Children's Centre, 685 Bannatyne Ave., Winnipeg, Manitoba, Canada R3E OWl. 0022-3476/78/0392-0429500.30/0 9 1978 The C. V. Mosby Co.
I1. 12. 13.
14.
429
LaPlante MP, Kaufman JJ, Goldman R, Gonick HC, Martin DC, and Goodwin WE: Kidney transplantation in children, Pediatrics 46:665, 1970. Cerilli GJ, Nelsen C, and Dorfman L: Renal transplantation in infants and children with the hemolytic-uremic syndrome, Surgery 71:66, 1972. Barnes BA, Bergan JJ, Braun WE, Fraumeni JF Jr, Kountz SL, Mickey MR, Rubin AL, Simmons RL, Stevens LE, and Wilson RE: The 12th report of the human renal transplant registry, JAMA 223:787, 1975. Gelfand MC, and Friedman EA: Prognosis of renal allotransplants in patients with bilateral renal cortical necrosis, Transplantation 10:442, 1970. Aronson AS, FOrst P, Kuylenstierna B, and Nyberg G: Essential amino acids in the treatment of advanced uremia, twenty-two months experience in a 5-year-old girl, Pediatrics 56:538, t975. Martin LW, Gonzalez LL, West CD, Swartz, RA, and Sntoruis DJ: Homotransplantation of both kidneys from an anencephalic monster to a 17 pound boy with Eagle-Barrett syndrome, Surgery 66:603, 1969. Kinne DW, Spanos PK, DeShazo MM, Simmons Rl~,and Najarian JS: Double renal transplants from pediatric donors to adult recipients, Am J Surg 127:292, 1974. Grushkin CM, and Fine RN: Growth in children following renal transplantation, Am J Dis Child 125:514, 1973. Faltiers CJ: Childhood asthma and steroid therapy as influences on growth, Am J Dis Child 105:127, 1963. Rappaport R, Cornu G, and Royner P: Statural growth in congenital adrenal hyperplasia treated with hydrocortisone~ J PEDIATR73:760, 1968. Potter D, Belzer FO, Rames L, Holliday MA, Kountz SL. and Najarian JS: The treatment of chronic uremia in childhood, I. Transplantation, Pediatrics 45:432, 1970.
two unrelated infants. Both conditions are rare and each may be inherited. W e report two infants with this association who were related to each other a n d who were b o t h products of c o n s a n g u i n e o u s matings. Possible explanations for concurrent inheritance o f these two conditions are discussed. CASE REPORTS Patient G. S. This term girl, birth weight 2.77 kg, was born in 1970 to a gravida 3, para 1 (one stillbirth) 26-year-old North American Indian. The parents were first cousins once removed (Fig. 1). Polyhydramnios occurred during the third trimester. The infant had persistent, nonbile-stained vomiting from birth but passed meconium. Bullae were first noted on day 2 on the left middle and index fingers; similar lesions appeared gradually on all skin surfaces. The patient became dehydrated, febrile, icteric, and developed seizures. At age 5 days, when transferred to the Health Sciences Children's Centre, Winnipeg, a radiograph of the abdomen demonstrated a single gastric bubble and a barium swallow showed complete obstruction at the pylorus. Laparotomy revealed a 2 cm fibrous cord at the pylorus and, on opening the stomach, no pyloric lumen could be demon-
430
,,
Brief clinical and laboratory observations
The Journal of Pediatrics March 1978
b
,,,
Autopsy performed 15 hours after death revealed areas of extensive loss of the epidermis, numerous healing skin lesions, and collapsed bullae. The nails of the fingers and toes were very dystrophic and were absent on both fifth toes. Microscopic sections of the skin lesions showed that the bullae were subepidermal, with cleavage between the basal layer of the epidermis and the dermis. In focal areas degenerating basal cells were evident. The basement membrane positive on periodic acid-Schiff stain remained attached to the dermis, which formed the base of the bullae. There were no macroscopic ulcers of the esophagus but microscopically there was cleavage between the epithelium and the underlying lamina propria, which represented bullous involvement of the esophagus similar to that present in the skin. DISCUSSION
Fig. 1. Pedigree diagram showing the relationship between the two families and the consanguinity of both sets of parents. strated. A posterior gastrojejunostomy was performed and the abdominal incision healed normally. Draining bullae developed at the sites of adhesive tape; by day 11, the mouth, pharynx, and nails were also involved. Old lesions healed without scarring. Postoperatively she tolerated formula feeds but by day 19. she developed bloody diarrhea and vomiting. This persisted and she developed anemia and hypoproteinemia (total proteins 2.4 gm/ dl) and failure to thrive. Repeat barium swallow showed good gastric emptying through the anastomosis. She died at 68 days of age, weighing 2.24 kg: Permission for autopsy was refused. Patient R. M. This term boy, birth weight 3.30 kg, was born in 1975 to a gravida 1, para 0, 23-year-old North American Indian. Polyhydramnios occurred during the pregnancy and delivery was by cesarean section because of cord prolapse. He was related to Patient G. S. through 1-2 and 1-3 who were brother and sister; his parents were second cousins (Fig. 1). He had persistent, nonbilestained vomiting from birth and did not pass meconium. An abdominal radiograph demonstrated a single gastric air bubble and no air in the intestine. He was transferred to this centre on day 2. Skin lesions were absent on admission. Laparotomy revealed a fibrous cord at the pylorus and no pyloric lumen could be demonstrated. A posterior gastrojejunostomy was performed and feedings were commenced on day 5. The incision healed well. On day three bullae were noted on the right ankle, left axilla, left groin, and back. The lesions became generalized and involved the skin, buccal mucosa, and nails. Old lesions healed without scarring. Biopsies of the foot lesions showed separation below the basal layers characteristic of epidermolysis bullosa dystrophica. He fed poorly, developed vomiting and diarrhea, and failed to thrive on gavage feedings supplemented by parenteral nutrition. Total parenteral nutrition (including Intralipid) was started on day 42 and continued for 43 days because of persistent bloody diarrhea, weight loss, and severe hypoproteinemia (total serum protein concentration < 2 gm/dl). The diarrhea and skin lesions persisted and were unresponsive to a 20-day course of prednisone (2.4 mg every six .hours) and a 28day course of cholestyramine (1 gm every six hours). He died on day 114, weighing 2.92 kg.
The simultaneous occurrence of epidermolysis bullosa and pyloric atresia in oui two patients (both type 2 atresias) and in the two children reported by Korber and atasson 1 is unlikely to represent a chance association. In all four patients the epidermolysis bullosa was felt to be of the autosomal recessive dystrophic type which occurs with a frequency of 1/106. Pyloric atresia also occurs with a frequency of about 1/10 ~ births; autosomal recessive inheritance is suggested by the fact that 21 of the 43 patients reported in the English literature ~-1~ have occurred in ten families (two related to each other, and in three the parents were consanguineous) with more than one affected sibling. Thus, epidermolysis bullosa dystrophica and pyloric atresia should occur together randomly only at a frequency of 1/101~ births. The parents in both families reported by Korber and CAasson, 1 and of o u r two patients were cousins; in addition, the families of our patients were closely related (Fig. 1). This supports the possibility that concurrence of epidermolysis bullosa and pyloric atresia represents the pleiotropic effect of a single gene. There are precedents for single genes causing both prenatal birth defects and an ongoing postnatal disease, in conditions such as Fanconi anemia. Although all four patients are believed to have had the recessive, dystrophic type of epidermolysis bullosa, none of them had scarring which is c o m m o n to this condition. Gedde-Dahl 1~ has pointed out that not all forms of recessive epidermolysis bullosa dystrophica have scarring and, as Korber and Glasson l have suggested, this may be evidence that a gene (or allele) other than that causing classic epidermolysis bullosa dystrophica is involved. Another hypothesis which cannot be ruled out on the basis of available information is that of close gene linkage between the gene for pyloric atresia and that causing epidermolysis bullosa. Based on the published incidence of the two conditions, one would expect approximately one person in 250,000 to be a carrier of both these
Volume 92 Number 3
B r i e f clinical and laboratory observations
autosomal recessive genes. I n order for b o t h conditions to occur in the same individual on the basis o f gene linkage, the two m u t a t i o n s would have to be in coupling, thus giving a "carrier" f r e q u e n c y o f only one in 500,000. R a n d o m m a t i n g b e t w e e n two unrelated carriers would b e extremely:urnlikely a n d consanguinity would be the rule. Additional affected families will be r e q u i r e d to clarify this matter. We thank Anne Coates, R.N., for her help in collecting the family history information and Mrs. L. Gordon for her secretarial assistance. Drs. C. W. Clark and T. Goodhand were closely involved with the surgical management of the first and second patients respectively.
4.
5.
6. 7. 8. 9.
REFERENCES 1. Korber JS, and Glasson MJ: Pyloric atresia associated with epidermolysis bullosa, J PEDIATR 90:600, 1977. 2. Talwalker VC: Pyloric atresia: A case report, J Pediatr Surg 2:458, 1967. 3. Bronsther B, Nadeau MR, and Abrams MW: Congenital
Inappropriate secretion of antidiuretic hormone complicating neonatal hypoxic-ischemic encephalopathy Sheldon L. Kaplan, M.D., and Ralph D. Feigin, M.D., St. Louis, Mo.
CEREBRAL EDEMA :nay complicate the m a n a g e m e n t o f infants with hypoxic-ischemic e n c e p h a l o p a t h y . 1 Since the acute onset of h y p o n a t r e m i a m a y be associated with increased b r a i n water content, recognition of the s y n d r o m e o f i n a p p r o p r i a t e gecretion o f antidiuretic h o r m o n e following p e r i n a t a l hypoxic-ischemic b r a i n injury is critical. In this situation, restriction of fluid m a y be required. The following case reports describe two infants with From the Edward Mallinckrodt Department o f Pediatrics and the Division o f Infectious Diseases at St. Louis Children's Hospital. Reprint address: Department of Pediatrics, Baylor College of Medicine, 1200 Moursund A re., Texas Medical Center, Houston, TX 77030.
0022-3476/78/0392-0431500.30/0 9 1978 The C. V. Mosby Co.
10. 11.
43 1
pyloric atresia: A report of three cases and a review of the literature, Surgery 69:130, 1971. Keramidas DC, and Voyatzis N: Pyloric atresia: Report of a second occurrence in the same family, J Pediatr Surg 7:445, 1972. Bar-Maor JA, Nissan S, and Nevo S: Pyloric atresia. A hereditary congenital anomaly with autosomal recessive transmission, J Med Genet 9:70, 1972. Saw EC, Arbegast NR, and Comer TP: Pyloric atresia: A case report, Pediatrics 51:574, 1973. Tan K, and Murugasu JJ: Congenital pyloric atresia in siblings, Arch Surg 106:100, 1973. Ducharme JC, and Bensoussan AL: Pyloric atresia, J Pediatr Surg 10:149, 1975. Melhelm RE, Salem G, Mishalany H, Slim M, and Der Kaloustian VM: Pyloroduodenal atresia. A report of three families with several similarly affected children, Pediatr Radiol 3:1, 1975. Olsen L, and Grotte G: Congenital pyloric atresia: Report of a familial occurrence, J Pediatr Surg 11:181, 1976. Gedde-Dahl T Jr: Epidermolysis bullosa. A clinical, genetic and epidemiological study, ed 1, Baltimore, 1971, The John Hopkins Press.
perinatal asphyxia, w h o developed h y p o n a t r e m i a . Inappropriate secretion o f A D H was d o c u m e n t e d by specific m e a s u r e m e n t o f p l a s m a arginine vasopressin concentrations a n d serum and urine chemistries. Plasma A V P was m e a s u r e d by r a d i o i m m u n o a s s a y as described by Skowsky a n d associates'-' and modified by W e i t z m a n , who kindly provided the a n t i b o d y to AVP.
Abbreviations used ADH: antidiuretic hormone SIADH: syndrome of inappropriate secretion of antidiuretic hormone AVP: arginine vasopressin BUN: bloodurea nitrogen CSF: cerebrospinal fluid
CASE REPORTS Case 1. A 2,900-gin girl was born to an 18-year-old mother after a 36-week, uncomplicated pregnancy. During labor irregular fetal heart tones of 80 per minute were observed and meconium staining of the anmiotic fluid was noted. The infant was delivered vaginally and had a tight nuchal cord. She was meconium stained and required resuscitation. At seven hours of age, seizure activity was observed; phenobarbital and 10% dextrose in water were administered intravenously. The infant was transferred to St. Louis Children's Hospital. On physical examination, the systolic blood pressure was 56 mm Hg. The infant was deeply obtunded and the anterior fontanel was tense. Pupils constricted on exposure to light. Muscle tone was increased moderately, more in the lower than in the upper extremities; deep tendon reflexes were 0-1 without clonus. No Moro, grasp, or suck reflexes could be elicited and no
B r i e f clinical and laboratory observations
similar to those in patients whose p r e t r a n s p l a n t a t i o n sera h a d cytotoxic antibodies. G r o w t h potential at the time of r e n a l t r a n s p l a n t a t i o n influences growth after t r a n s p l a n t a t i o n . 11 Since growth velocity is greatest d u r i n g the first year of life, one m i g h t expect a n i n f a n t who receives a k i d n e y t r a n s p l a n t a n d m a i n t a i n s good renal function to grow well. Despite doses of prednisone o f 35.7 m g / m ~ in the i m m e d i a t e posttransp l a n t period a n d 13.5 m g / m ~ at the present time, o u r patient has s h o w n n o r m a l growth velocity. It has b e e n previously stated that p r e d n i s o n e in excess of 10 m g / m ~ / day adversely affected n o r m a l growth in children with o t h e r disease states ~' 1:~ a n d in allograft r e c i p i e n t s ? ' O n the basis o f our experience, we believe it is w o r t h a t t e m p t i n g a renal t r a n s p l a n t in infants, since chronic dialysis rarely results in a d e q u a t e growth a n d develo pment. This therapy m a y offer the child the best opportunity to resume growth if renal f u n c t i o n is m a i n t a i n e d .
4.
5.
6.
7.
8.
9.
10.
REFERENCES
1. Fine RN, Korsch BM, Brennan LP, Edelbrock HH, Stiles QR, Riddell HI, Weitzman JJ, Mickelson JC, Tucker BL, and Grushkin CM: Renal transplantation in young children, Am J Surg 125:559, 1973. 2. Lawson RK, Talwalkar YB, Musgrave JE, Campbell RA, and Hodges CV: Renal transplantation in pediatric patients, J Urol 113:225, 1975. 3. DeShazo CV, Simmons RL, Bernstein DM, DeShazo MM, Willmert J, Kjellstrand CM, and Najarian JS: Results of renal transplantation in 100 children, Surgery 76:461, 1974.
Familial pyloric atresia associated with epidermolysis bullosa William G. D e Groot, M . D . , Ray Postuma, M . D . , * and Alasdair G. W. Hunter, M . D . ,
Winnipeg, Manitoba, Canada
P'r I~o R I C A'r R E S I A associated with epidermolysis bullo-
sa was first reported in 1976 by K o r b e r a n d Glasson I in
From the Departments of Pediatrics and Surgery, Health Sciences Children's Centre, and University of Manitoba. *Reprint address: Health Sciences Children's Centre, 685 Bannatyne Ave., Winnipeg, Manitoba, Canada R3E OWl. 0022-3476/78/0392-0429500.30/0 9 1978 The C. V. Mosby Co.
I1. 12. 13.
14.
429
LaPlante MP, Kaufman JJ, Goldman R, Gonick HC, Martin DC, and Goodwin WE: Kidney transplantation in children, Pediatrics 46:665, 1970. Cerilli GJ, Nelsen C, and Dorfman L: Renal transplantation in infants and children with the hemolytic-uremic syndrome, Surgery 71:66, 1972. Barnes BA, Bergan JJ, Braun WE, Fraumeni JF Jr, Kountz SL, Mickey MR, Rubin AL, Simmons RL, Stevens LE, and Wilson RE: The 12th report of the human renal transplant registry, JAMA 223:787, 1975. Gelfand MC, and Friedman EA: Prognosis of renal allotransplants in patients with bilateral renal cortical necrosis, Transplantation 10:442, 1970. Aronson AS, FOrst P, Kuylenstierna B, and Nyberg G: Essential amino acids in the treatment of advanced uremia, twenty-two months experience in a 5-year-old girl, Pediatrics 56:538, t975. Martin LW, Gonzalez LL, West CD, Swartz, RA, and Sntoruis DJ: Homotransplantation of both kidneys from an anencephalic monster to a 17 pound boy with Eagle-Barrett syndrome, Surgery 66:603, 1969. Kinne DW, Spanos PK, DeShazo MM, Simmons Rl~,and Najarian JS: Double renal transplants from pediatric donors to adult recipients, Am J Surg 127:292, 1974. Grushkin CM, and Fine RN: Growth in children following renal transplantation, Am J Dis Child 125:514, 1973. Faltiers CJ: Childhood asthma and steroid therapy as influences on growth, Am J Dis Child 105:127, 1963. Rappaport R, Cornu G, and Royner P: Statural growth in congenital adrenal hyperplasia treated with hydrocortisone~ J PEDIATR73:760, 1968. Potter D, Belzer FO, Rames L, Holliday MA, Kountz SL. and Najarian JS: The treatment of chronic uremia in childhood, I. Transplantation, Pediatrics 45:432, 1970.
two unrelated infants. Both conditions are rare and each may be inherited. W e report two infants with this association who were related to each other a n d who were b o t h products of c o n s a n g u i n e o u s matings. Possible explanations for concurrent inheritance o f these two conditions are discussed. CASE REPORTS Patient G. S. This term girl, birth weight 2.77 kg, was born in 1970 to a gravida 3, para 1 (one stillbirth) 26-year-old North American Indian. The parents were first cousins once removed (Fig. 1). Polyhydramnios occurred during the third trimester. The infant had persistent, nonbile-stained vomiting from birth but passed meconium. Bullae were first noted on day 2 on the left middle and index fingers; similar lesions appeared gradually on all skin surfaces. The patient became dehydrated, febrile, icteric, and developed seizures. At age 5 days, when transferred to the Health Sciences Children's Centre, Winnipeg, a radiograph of the abdomen demonstrated a single gastric bubble and a barium swallow showed complete obstruction at the pylorus. Laparotomy revealed a 2 cm fibrous cord at the pylorus and, on opening the stomach, no pyloric lumen could be demon-
430
,,
Brief clinical and laboratory observations
The Journal of Pediatrics March 1978
b
,,,
Autopsy performed 15 hours after death revealed areas of extensive loss of the epidermis, numerous healing skin lesions, and collapsed bullae. The nails of the fingers and toes were very dystrophic and were absent on both fifth toes. Microscopic sections of the skin lesions showed that the bullae were subepidermal, with cleavage between the basal layer of the epidermis and the dermis. In focal areas degenerating basal cells were evident. The basement membrane positive on periodic acid-Schiff stain remained attached to the dermis, which formed the base of the bullae. There were no macroscopic ulcers of the esophagus but microscopically there was cleavage between the epithelium and the underlying lamina propria, which represented bullous involvement of the esophagus similar to that present in the skin. DISCUSSION
Fig. 1. Pedigree diagram showing the relationship between the two families and the consanguinity of both sets of parents. strated. A posterior gastrojejunostomy was performed and the abdominal incision healed normally. Draining bullae developed at the sites of adhesive tape; by day 11, the mouth, pharynx, and nails were also involved. Old lesions healed without scarring. Postoperatively she tolerated formula feeds but by day 19. she developed bloody diarrhea and vomiting. This persisted and she developed anemia and hypoproteinemia (total proteins 2.4 gm/ dl) and failure to thrive. Repeat barium swallow showed good gastric emptying through the anastomosis. She died at 68 days of age, weighing 2.24 kg: Permission for autopsy was refused. Patient R. M. This term boy, birth weight 3.30 kg, was born in 1975 to a gravida 1, para 0, 23-year-old North American Indian. Polyhydramnios occurred during the pregnancy and delivery was by cesarean section because of cord prolapse. He was related to Patient G. S. through 1-2 and 1-3 who were brother and sister; his parents were second cousins (Fig. 1). He had persistent, nonbilestained vomiting from birth and did not pass meconium. An abdominal radiograph demonstrated a single gastric air bubble and no air in the intestine. He was transferred to this centre on day 2. Skin lesions were absent on admission. Laparotomy revealed a fibrous cord at the pylorus and no pyloric lumen could be demonstrated. A posterior gastrojejunostomy was performed and feedings were commenced on day 5. The incision healed well. On day three bullae were noted on the right ankle, left axilla, left groin, and back. The lesions became generalized and involved the skin, buccal mucosa, and nails. Old lesions healed without scarring. Biopsies of the foot lesions showed separation below the basal layers characteristic of epidermolysis bullosa dystrophica. He fed poorly, developed vomiting and diarrhea, and failed to thrive on gavage feedings supplemented by parenteral nutrition. Total parenteral nutrition (including Intralipid) was started on day 42 and continued for 43 days because of persistent bloody diarrhea, weight loss, and severe hypoproteinemia (total serum protein concentration < 2 gm/dl). The diarrhea and skin lesions persisted and were unresponsive to a 20-day course of prednisone (2.4 mg every six .hours) and a 28day course of cholestyramine (1 gm every six hours). He died on day 114, weighing 2.92 kg.
The simultaneous occurrence of epidermolysis bullosa and pyloric atresia in oui two patients (both type 2 atresias) and in the two children reported by Korber and atasson 1 is unlikely to represent a chance association. In all four patients the epidermolysis bullosa was felt to be of the autosomal recessive dystrophic type which occurs with a frequency of 1/106. Pyloric atresia also occurs with a frequency of about 1/10 ~ births; autosomal recessive inheritance is suggested by the fact that 21 of the 43 patients reported in the English literature ~-1~ have occurred in ten families (two related to each other, and in three the parents were consanguineous) with more than one affected sibling. Thus, epidermolysis bullosa dystrophica and pyloric atresia should occur together randomly only at a frequency of 1/101~ births. The parents in both families reported by Korber and CAasson, 1 and of o u r two patients were cousins; in addition, the families of our patients were closely related (Fig. 1). This supports the possibility that concurrence of epidermolysis bullosa and pyloric atresia represents the pleiotropic effect of a single gene. There are precedents for single genes causing both prenatal birth defects and an ongoing postnatal disease, in conditions such as Fanconi anemia. Although all four patients are believed to have had the recessive, dystrophic type of epidermolysis bullosa, none of them had scarring which is c o m m o n to this condition. Gedde-Dahl 1~ has pointed out that not all forms of recessive epidermolysis bullosa dystrophica have scarring and, as Korber and Glasson l have suggested, this may be evidence that a gene (or allele) other than that causing classic epidermolysis bullosa dystrophica is involved. Another hypothesis which cannot be ruled out on the basis of available information is that of close gene linkage between the gene for pyloric atresia and that causing epidermolysis bullosa. Based on the published incidence of the two conditions, one would expect approximately one person in 250,000 to be a carrier of both these
Volume 92 Number 3
B r i e f clinical and laboratory observations
autosomal recessive genes. I n order for b o t h conditions to occur in the same individual on the basis o f gene linkage, the two m u t a t i o n s would have to be in coupling, thus giving a "carrier" f r e q u e n c y o f only one in 500,000. R a n d o m m a t i n g b e t w e e n two unrelated carriers would b e extremely:urnlikely a n d consanguinity would be the rule. Additional affected families will be r e q u i r e d to clarify this matter. We thank Anne Coates, R.N., for her help in collecting the family history information and Mrs. L. Gordon for her secretarial assistance. Drs. C. W. Clark and T. Goodhand were closely involved with the surgical management of the first and second patients respectively.
4.
5.
6. 7. 8. 9.
REFERENCES 1. Korber JS, and Glasson MJ: Pyloric atresia associated with epidermolysis bullosa, J PEDIATR 90:600, 1977. 2. Talwalker VC: Pyloric atresia: A case report, J Pediatr Surg 2:458, 1967. 3. Bronsther B, Nadeau MR, and Abrams MW: Congenital
Inappropriate secretion of antidiuretic hormone complicating neonatal hypoxic-ischemic encephalopathy Sheldon L. Kaplan, M.D., and Ralph D. Feigin, M.D., St. Louis, Mo.
CEREBRAL EDEMA :nay complicate the m a n a g e m e n t o f infants with hypoxic-ischemic e n c e p h a l o p a t h y . 1 Since the acute onset of h y p o n a t r e m i a m a y be associated with increased b r a i n water content, recognition of the s y n d r o m e o f i n a p p r o p r i a t e gecretion o f antidiuretic h o r m o n e following p e r i n a t a l hypoxic-ischemic b r a i n injury is critical. In this situation, restriction of fluid m a y be required. The following case reports describe two infants with From the Edward Mallinckrodt Department o f Pediatrics and the Division o f Infectious Diseases at St. Louis Children's Hospital. Reprint address: Department of Pediatrics, Baylor College of Medicine, 1200 Moursund A re., Texas Medical Center, Houston, TX 77030.
0022-3476/78/0392-0431500.30/0 9 1978 The C. V. Mosby Co.
10. 11.
43 1
pyloric atresia: A report of three cases and a review of the literature, Surgery 69:130, 1971. Keramidas DC, and Voyatzis N: Pyloric atresia: Report of a second occurrence in the same family, J Pediatr Surg 7:445, 1972. Bar-Maor JA, Nissan S, and Nevo S: Pyloric atresia. A hereditary congenital anomaly with autosomal recessive transmission, J Med Genet 9:70, 1972. Saw EC, Arbegast NR, and Comer TP: Pyloric atresia: A case report, Pediatrics 51:574, 1973. Tan K, and Murugasu JJ: Congenital pyloric atresia in siblings, Arch Surg 106:100, 1973. Ducharme JC, and Bensoussan AL: Pyloric atresia, J Pediatr Surg 10:149, 1975. Melhelm RE, Salem G, Mishalany H, Slim M, and Der Kaloustian VM: Pyloroduodenal atresia. A report of three families with several similarly affected children, Pediatr Radiol 3:1, 1975. Olsen L, and Grotte G: Congenital pyloric atresia: Report of a familial occurrence, J Pediatr Surg 11:181, 1976. Gedde-Dahl T Jr: Epidermolysis bullosa. A clinical, genetic and epidemiological study, ed 1, Baltimore, 1971, The John Hopkins Press.
perinatal asphyxia, w h o developed h y p o n a t r e m i a . Inappropriate secretion o f A D H was d o c u m e n t e d by specific m e a s u r e m e n t o f p l a s m a arginine vasopressin concentrations a n d serum and urine chemistries. Plasma A V P was m e a s u r e d by r a d i o i m m u n o a s s a y as described by Skowsky a n d associates'-' and modified by W e i t z m a n , who kindly provided the a n t i b o d y to AVP.
Abbreviations used ADH: antidiuretic hormone SIADH: syndrome of inappropriate secretion of antidiuretic hormone AVP: arginine vasopressin BUN: bloodurea nitrogen CSF: cerebrospinal fluid
CASE REPORTS Case 1. A 2,900-gin girl was born to an 18-year-old mother after a 36-week, uncomplicated pregnancy. During labor irregular fetal heart tones of 80 per minute were observed and meconium staining of the anmiotic fluid was noted. The infant was delivered vaginally and had a tight nuchal cord. She was meconium stained and required resuscitation. At seven hours of age, seizure activity was observed; phenobarbital and 10% dextrose in water were administered intravenously. The infant was transferred to St. Louis Children's Hospital. On physical examination, the systolic blood pressure was 56 mm Hg. The infant was deeply obtunded and the anterior fontanel was tense. Pupils constricted on exposure to light. Muscle tone was increased moderately, more in the lower than in the upper extremities; deep tendon reflexes were 0-1 without clonus. No Moro, grasp, or suck reflexes could be elicited and no
