Second family with “apple peel” syndrome affecting four siblings: Autosomal recessive inheritance confirmed

  • Published on

  • View

  • Download

Embed Size (px)


  • American Journal of Medical Genetics 42119-121 (1993)

    Letter to the Editor

    Second Family With Apple Peel Syndrome Affecting Four Siblings: Autosomal Recessive Inheritance Confirmed

    To the Editor:

    There is evidence that some familial congenital small bowel atresia cases may be associated with autosomal recessive mode of inheritance. A proposed classification, based on clinical and morphological characteristics of 59 infants with jejunal and ileal atresia, was published by Martin et al. [19761. This includes 4 subtypes: type I, membrane (13 cases = 22%); type 11, bowel discontinu- ity (32 cases = 54.2%); type 111, multisystem (7 cases = 11.9%); and type IV, apple peel syndrome (7 cases = 11.9%). In 1979, Grosfeld et al. reported their experience with 62 cases with different intestinal atresias (23 duo- denal, 15 jejunal, 18 ileal, and 6 colonic). They classified 33 cases with jejunoileal atresias to five distinguished morpholocial patterns: type I, septa1 atresia (2 cases = 6.1%); type 11, fibrous cord joining atretic ends (7 cases = 21.2%); type IIIA, atretic ends separated and associ- ated with V-shaped mesenteric defect (14 cases = 42.4%); type IIIB, apple peel atresia (4 cases = 12.1%); and type IV, multiple atresias (6 cases = 13.2%).

    In 1961, Santulli and Blanc first used the term apple peel jejunal atresia when they described 3 patients in their review of 76 neonates, with small bowel atresia. Other eponyms for the condition include Christmas tree, maypole, and pagoda bowel [Weitzman and Vanderhoof, 1966; Dickson, 1970; Nixon and Towes, 19711. This well defined variant of high jejunal atresia is characterised by helical ileum and prenatal occlusion of the superior mesenteric artery with retrograde blood supply to the surviving distal small bowel from the right colic vessels [Seashore et al., 19871. Mishalany and Naj- jar 119683 reported 3 affected Lebanese sibs with charac- teristic morphological configuration. The 4th died at home with congenital high intestinal obstruction out of 18 offspring of first cousin parents. They suggested the possibility of an autosomal recessive mode of inheri- tance. In 1969, Blyth and Dickson reported 8 cases of apple peel syndrome (APS) including 2 cases in 2 fami-

    Received for publication August 31, 1992; revision received December 18, 1992.

    Address reprint requests to Dr. Farag, Jahra Regional Liaison Community Genetics Programme, P.O. Box: 31145, Sulibikhat, 90802, Kuwait.

    0 1993 Wiley-Liss, Inc.

    lies with 2 affected sibs. In 1971, Rickhman and Karplus briefly mentioned 2 affected sibs. Al-Awadi et al. [19811 reported 2 affected sibs out of 3 offspring of healthy first cousin Saudi Arabian parents: the first with type IIIB and the second with type IIIA atresia according to Grosfeld et al. [19791 classification. Seashore et al. [1987] reported 2 sisters with APS.

    The second Arab family with 4 sibs having the clini- cal, roentographic and morphological features of jejunal atresia with apple peel variant is reported, confirming autosomal recessive mode of inheritance. The first two affected sibs (Fig. 1: VI-1 and VI-2) were previously reported [Farag and Teebi, 19891. Despite the one in 4 risk, the woman delivered 2 other babies with the same problem.

    Case No. 3 (Fig. 1: VI-3). A full term 2,160 g female was delivered in 1988. She was suspected of having the same congenital small bowel obstruction after prenatal ultrasonographic examination. A plain abdominal X-ray confirmed the diagnosis. Laparatomy showed jejunal


    P $ m V v

    Fig. 1. Family pedigree.

  • 120 Farag et al.

    TABLE I. The Biological and Phenotypic Variables of the Four Palestinian Sibs With Apple Peel Syndrome 1 2 3 4


    Fig. 1 VI-1 VI-2 VI-3 VI-6 DOB March 86 June 87 May 88 August 91 Sex M M F M Polyhydrominos + + + + Prenatal ultrasonography (high bowel obstruction) + + + + Gestation (wks) 39 36 40 31 Birth weight (g) 2,800 2,250 2,160 2,680 Clinical diagnosis

    Repeated greenish vomiting + + + + No meconium + + + +

    X-ray abdomen Jejunal obstruction + + + +

    Resection anastomosis (h) 9 10 6 4 Morphological diagnosis

    Atresia from duodeno jejunal flexure (cm) 7 10 9 8 Apple peel syndrome + + + + Mesenteric cyst + + Intrauterine volvulus

    - - + - - -

    Postoperative survival (days) 60 30 40 67

    atresia with apple peel variant. Resection anastomo- sis was done. The baby died 40 days after the operation.

    A male was born in 1991, after delivery of a phenotypically normal girl and one early spontaneous abortion. His birth weight was 2,680 g. Abdominal X-ray confirmed the diagnosis. The baby was referred to the pediatric surgeon within 4 hours. Laparatomy showed upper jejunal atresia; gangrene of the rest of small gut with 5 x 2.5 x 1 cm mass proved to be intrauterine volvulus by histopathological study. Re- section anastomosis was done. The baby died 67 days after the operation. The biological and phenotypical variables of the 4 affected sibs are summarized in Table I. The finding of a mesenteric cyst in 2 cases is interest- ing since basically, APS cases have no mesentery.

    It seems that the mortality rate of APS cases is much higher than in simple jejunal atresias (types I and 11) because of deficient collateral circulation to the small intestine [Leonidas et al., 19761. Postoperative mortal- ity rate among infants with APS in the 3 Arab studies was 100% [Mishalany and Najar, 1968; Al-Awadi et al., 1981; Farag and Teebi, 19891. Zivkovic and Millosevic [19791 showed 65% mortality rate among surgically treated APS cases. Seashore et al. L19871 reported lower mortality rate (54%) among 57 APS cases. Recently, Turnock et al. [19911 reported a survival rate of 100% in 12 neonates with APS treated surgically, 10 of whom required parentral nutrition.

    The most widely accepted theory regarding the patho- genesis of APS is a prenatal vascular occlusion of the superior mesenteric artery resulting in aseptic necrosis of part of the small intestine [Louw and Barnard, 1955; Blanc et al., 1959; Santulli and Blanc, 1961; Weitzman and Vanderhoof, 1966; Abrams, 1960; Dickson, 1970; Zwiren et al., 1972; Leonidas et al., 19761. Such lesions are generally unassociated with other anomalies but may be seen in cases of meconium ileus due to cystic fibrosis [Winter et al., 1989; Bernstein et al., 19601. Eight cases with cystic fibrosis, among the 59 infants with different atresias (13.6%) were detected by Martin

    Case No. 4 (Fig. 1: VI-6).

    et al. [19761. All were type I and type I1 atresia. Lower figure was reported by Grosfeld et al. [19791 who de- tected one case with cystic fibrosis among 33 patients with jejunoileal atresias (3%).

    The present report of the second Arab family with 4 affected sibs having APS confirms autosomal recessive mode of inheritance. The pedigree in both this Palesti- nian family and the Lebanese family [Mishalany and Naiar, 19681, showing 4 afYected sibs of both sexes, and healthy consanguineous parents, is informative. In practical genetic counselling, the empiric recurrence risk of isolated small bowel atresias is less than 5%. In general, the recurrence of APS in families has been explained on multifactorial basis. However, among the much more numerous multifactorial cases are a few APS cases of autosomal recessive causation. When ge- netic counselling is given to the parents of children affected with intestinal atresia, the possibility that some of these may be familial should not be overlooked. Due caution should be exercised in stating the recur- rence risk in communities with high average inbreeding coeflicient, large family size, poor response to genetic counselling, and plethora of autosomal recessive men- delizing gene disorders [Al-Awadi et al., 1981; Farag and Al-Awadi, 1988; Farag and Teebi, 19891.

    REFERENCES Abrams JS (1960): Experimental intestinal atresia. Surgery 64:185. Al-Awadi SA, Farag TI, Naguib K, Cuschieri A, h a M (1981): Familial

    jejunal atresia with apple-peel variant. J Roy Soc Med 74499-501. Bernstein J, Vawter G, Harris GBC, Young V (1960): The occurrence of

    intestinal atresia in newborns with meconium ileus. Am J Dis Child

    Blanc WA, Santulli TV, Anderson DH (1959): Pathogenesis of je- junoileal atresia. Am J Dis Child 98564-565.

    Blyth H, Dickson JAS (1969): Apple-peel syndrome (congenital intesti- nal atresia): A family study of seven index patients. J Med Genet 6:275-277.

    Dickson JA (1970): Apple-peel bowel: An uncommon variant of duode- nal and jejunal atresia. J Pediatr Surg 5:595-600.


  • Letter to the Editor 121 apple-peel jejunal atresia: Surgical, genetic and radiographic as- pects. Pediatrics 80:540-544.

    fimock RR, Bereton RJ, Spitz L, Kiely EM (1991): primary anastomo- sis in apple-peel bowel syndrome. J Pediatr Surg 26718-720.

    Weitzman JJ , Vanderhoof RS (1966): Jejunal atresia with agenesis of the dorsal mesentery with Christmas tree deformity of the small intestine. Am J Surg 111:443-449.

    Winter RM, Knowles SAS, Bieber FR, Baraitser M (1989): The Mal- formed Fetus and Stillbirth: A Diagnostic Approach. Chichester: John Wiley & Sons, 140-143.

    Zarella JT, Martin LW (1976): Jejunal atreaia with absent mesentery and a helical ileum. Surgery 80550-553.

    Zivkovic SM, Millosevic VR (1979): Duodenal and jejunal atresia with agenesis of the dorsal mesentery: Apple-peel small bowel. Am J Surg 137:676-778.

    Zwiren GT, Andrews HG, Ahmann P (1972): Jejunal atresia with agenesis of the dorsal mesentery apple-peel small bowel. J Pediatr Surg 7:414-419.

    Talaat I. Farag Sadika A. Al-Awadi Magda H. El-Badramany R. Usha Mohammed El-Ghanem Jahra Regional Liaison Community Genetics Programme Sulibikhat, Kuwait

    Farag TI, Al-Awadi SA (1988): Strategies in liaison and regional com- munity genetic services in developing communities: A lesson from the Amish. Clin Genet 34:395.

    Farag TI, Teebi AS (1989): Apple-peel syndrome in sibs. J Med Genet 2657-68.

    Grosfeld JL, Ballantine TVN, Shoemaker R (1979): Operative manage- ment of intestinal atresia and stenosis based on pathological find- ings. J Paediatr Surg 14368-375.

    Leonidas JC, Amoury RA, Ashcraft KW, Fellow RA (1976): Duodeno- jejunal atresia with apple-peel small bowel. Pediatr Radio 118: 661-665.

    Louw JH, Barnard GN (1955): Congenital intestinal atresia, observa- tions on its origin. Lancet 2:1065-1067.

    MartinCE, Leonidas JC, Amoury RA (1976): Multiple gastrointestinal atresias with intraluminal calcifications and cystic dilatation of bile ducts: A newly recognised entity resembling a string of pearls. Pediatrics 57:263-271.

    Mishalany HG, Najjar FB (1968): Familial jejunal atresia: Three cases in one family. J Paediatr 73:753-755.

    Nixon HH, lbwes R (1971): Etiology and treatment of small intestinal atresia: Analysis of a series of 127 jejunoileal atresias and compari- son with duodenal atresia. Surgery 6941.

    Rickham PP, Karplus M (1971): Familial and hereditary intestinal atresia. Faediatrics 73:753-755.

    Santulli TV, Blanc WA (1961): Congenital atresia of the intestine: Pathogenesis and treatment. Ann Surg 154:939-948.

    Seashore JH, Francis SC, Markowitz RI, Seashore MR (1987): Familial


View more >