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Mirror-image gastroschisis in monochorionic female twins
European Journal of Medical Genetics 58 (2015) 266e269
Contents lists available at ScienceDirect
European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg
Clinical report
Mirror-image gastroschisis in monochorionic female twins Toni Kasole Lubala a, Sébastien Mbuyi-Musanzayi b, Nina Lubala c, Oscar Numbi Luboya a, Prosper Muenze Kalenga d, Koenraad Devriendt e, *, Prosper Lukusa-Tshilobo e, f a
Department of Pediatrics, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo Department of Surgery, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo c Department of Ophthalmology, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo d Department of Gynecology and Obstetrics, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo e Center for Human Genetics, University Hospitals, KU Leuven, P.O. Box 602, 3000 Leuven, Belgium f Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, Democratic Republic of the Congo b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 October 2014 Accepted 8 March 2015 Available online 14 March 2015
We report a case of “mirror-image” gastroschisis in female monochorionic twins. One of the twins presents a right-sided gastroschisis, the other a left-sided gastroschisis. Both twins have anteriorly placed anus and sacral dimple. To the best of our knowledge, this represents the first case of mirror image or discordant left and right gastroschisis in monochorionic twins reported in the literature. This observation may shed further light on the pathogenesis of gastroschisis. Ó 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Gastroschisis Left Right Sacral dimples Monochorionic twins
1. Introduction Gastroschisis is a herniation of abdominal content through a paramedian full-thickness abdominal defect [Jones et al., 2009]. During the past 30 years, its incidence has increased 10e20 fold worldwide, with clear regional variations [Bradnock et al., 2011; Valdèz et al., 2011]. The etiology of gastroschisis is still unclear. Five different theories have been proposed to explain the pathogenesis of this anomaly, but none of them is totally compatible with the current knowledge in human embryology [reviewed by Feldkamp et al., 2007; Valdèz et al., 2011]. Two main embryological hypothesis have been previously proposed: deVries [1980] suggested that abnormal involution of the right umbilical vein leads to adverse effects on the adjacent mesoderm, followed by the subsequent rupture of the body wall. In the second theory, Hoyme et al. [1981] suggest that gastroschisis results from an intrauterine interruption of the omphalomesenteric artery witch causes infarction and necrosis of the base of the umbilical cord, rupture of the body wall and intestinal herniation through the defect.
* Corresponding author. Tel.: þ32 16 34 59 03; fax: þ32 16 34 60 60. E-mail address: [email protected] (K. Devriendt). http://dx.doi.org/10.1016/j.ejmg.2015.03.001 1769-7212/Ó 2015 Elsevier Masson SAS. All rights reserved.
More recently, Feldkamp et al. [2007] suggested that gastroschisis could be considered as a ventral body wall malformation rather than a vascular disruption. Right-sided gastroschisis is the most common form, the leftsided one being exceptional. In fact, only about 20 cases of leftsided gastroschisis were reported from 1988 to 2010 [Mandelia et al., 2013]. We report monochorionic female twins who both presented at birth a gastroschisis, but discordant regarding the right/left sided location. 2. Clinical report Diamniotic monochorionic female twins were vaginally born at term and referred to us on day three for gastroschisis. The parents are not consanguineous, the father was 28 years old, the mother 19 years. They had an elder brother, alive and healthy. Family history is negative with regard to congenital malformations. The mother denied substance abuse (alcohol or tobacco) and there were no infections during pregnancy. However, the mother did not have any prenatal consultation during pregnancy nor did she receive the required periconceptional folic acid supplementation. On clinical examination, both twins were small for date, with weight 1900 g (2, 7 SD e CDC growth chart), length 49 cm (P50) and head circumference 35 cm (P50). There was no facial
T.K. Lubala et al. / European Journal of Medical Genetics 58 (2015) 266e269
dysmorphism. A large abdominal wall defect was noted in both twins (Fig. 1). In the first twin, the abdominal wall defect was situated on the right side, 2 cm from an intact umbilical cord and there was a herniation of the liver together with oedematous and thickened small bowel loops. In the second twin, the defect was left-sided, about 2.5 cm from the umbilical cord with evisceration of oedematous small bowel loops. The clinical examination also revealed an anteriorly placed anus (Fig. 2). A lumbosacral dimple was observed in both of them, possibly indicating an underlying lumbosacral spine defect. No radiographs could be obtained (Fig. 3). They died on day 4 and day 6, respectively, before any surgery could be performed because they were in a very poor medical condition, with already seriously affected small bowel. 3. Discussion We here report the unique observations of female monochorionic twins who were concordant for a gastroschisis, but discordant regarding the left or right sided position. Whereas in one twin the defect was right sided, as most commonly seen, in the other it was on the left side, which is exceptional. Thus the monochorionic twins presented a “mirror-image” gastroschisis. This observation may shed light on the pathogenesis of gastroschisis. Currently, the exact etiology of gastroschisis is not well understood. The first report of a gastroschisis in twins reported a male and female dizygotic twins concordant for a right-sided gastroschisis [Sarda and Bard, 1984]. More recently, Bugge et al. described for the first time a pair of monozygotic female twins discordant for a right-sided gastroschisis [Bugge et al., 1994]. In a twin study, Schultz et al. [2012] found that the concordance rate was not significantly different amongst dizygotic twins (4 out of 8 twins) compared to monozygotic twins (2 out of 5 twins reported). If we include our case with concordant gastroschisis, 3 out of 6 monozygotic twins are concordant, which is equal the concordance observed in dizygotic twins. However, it should be noted that the number of reported twins with gastroschisis is very small so we cannot evaluate the relative contribution of genetic versus environmental factors. One of the non-genetic factors identified is young maternal age, with an increased risk (7
267
times) for the mothers between the ages 14 and 19. In our case, the young maternal age (19 years) might have contributed to the gastroschisis [Valdéz et al., 2011]. How young maternal age may influence the risk is not known, but some studies reported an association with life-style factors, e.g. consuming alcohol, cocaïne and tobacco [Polifka and Friedman, 1999], medication such as misoprostol and cyclooxygenase inhibitors like aspirin and Ibuprofen and pseudoephedrine during pregnancy. [Polifka and Friedman, 1999; Werler, 2006; Werler et al., 2002]. The world-wide increase in incidence of gastroschisis during the last ten years may be related to unknown risk factors related to the lifestyle in young mothers. This association with vasoactive agents supports a vascular disruption pathogenesis, at least in a subset of cases [Torfs et al., 1996]. A vascular disruption would also explain the frequent association of gastroschisis with intestinal atresia and stenosis, also thought to have a vascular disruption origin [Werler et al., 2002]. There was no history of exposure to any of these substances in our case. However, the mother did not receive periconceptional folic acid supplementation. Some authors consider this supplementation as having a protective effect [Paranjothy et al., 2012]. Beside those non-genetic factors, a multifactorial origin of gastroschisis is suggested by the existence of familial cases, with an empiric recurrent risk of 3, 5%, and the observed positive association between gastroschisis and variants in genes linked to angiogenesis [Feldkamp et al., 2007]. Feldkamp et al. [2007] suggested an unifying hypothesis on the origin of most ventral wall defects, including gastroschisis, cloacal exstrophy or ectopia cordis. These authors furthermore suggested that the different processes that impact ventral wall closure might also contribute to neural tube closure [Feldkamp et al., 2007]. This could explain the concomitant presence of gastroschisis and sacral dimples in both monozygotic twins in our observation. One intriguing observation is the “mirror-image” position of the gastroschisis in these monochorionic twins. This has not been reported before. Several monozygotic twins have been reported with mirror-image unilateral malformations in other organs or regions of the body (see Table 1). This may suggest a pathogenic
Fig. 1. (A) large anterior abdominal wall defect on patient’s the right side of the umbilical cord with an eviscerated, oedematous and thickened liver and part of the small bowel loops for the first twin. (B) In the second twin, the abdominal wall defect was on patient’s left side of the umbilical cord with eviscerated and oedematous small bowel loops.
268
T.K. Lubala et al. / European Journal of Medical Genetics 58 (2015) 266e269
Fig. 2. Anteriorly placed position of the anus in both twins.
Fig. 3. Sacral dimples in both twins.
relationship between mirror-image asymmetry and the process of twinning. However, one has to be cautious, since these are all single case reports, and therefore, it is not excluded that the concept of mirrorimage of malformations in monozygotic twins are chance observations and that the case reports represent an ascertainment and Table 1 Overview of reported mirror-image anomalies reported in monozygotic twins. Affected system
Defect
Nervous Arachnoid cyst system Arachnoid cyst Eye Optic nerve hypoplasia Myopic anisometropia Unilateral keratoconus Esotropia Lacrymal fistula Myopic anisometropia Esotropia Ear Microtia Orofacial Double teeth with hypodontia Mandibular incisor/canine fusion Cleft lip/palate Cleft lip/palate Cleft lip/palate Clefs lip/palate Hip cysts Limbs Solitary bone cyst of the humerus
Country
Study
Year
Norway China USA Japan France Australia Turkey Korea Serbia USA Malaysia
2007 2011 1997 2001 2007 2009 2010 2010 2011 2011 1987
Canada
Helland and Wester Zhou et al. Cidis et al. Okamoto et al. Aknin et al. Dirani et al. Deveer et al. Kim et al. Stankovi c-Babi c et al. Brent Nik-Hussein and Salcedo Sperber et al.
1994
Japan Brazil Turkey Germany USA Japan
Satoh et al. da Silva et al. Deveer et al. Reiss et al. Song et al. Goto et al.
1995 2008 2010 2012 2013 2008
publication bias. In accordance with this, no higher degree of facial asymmetry was observed in monozygotic twins compared to dizygotic twins [Burke and Healy, 1993; Djordjevic et al., 2013]. On the other hand, in the only systematic twin study we were able to ascertain, a discordance in the clockwise or counterclockwise direction of crown whorl of the head hair was much higher in identical (15/47) than in fraternal twins (5/48) [Newman, 1928]. This suggests that the process of twinning is associated with disturbance of a mechanism establishing (a) symmetry. Alternatively, an underlying defect in establishing (a) symmetry may be at the basis of the twinning process. There is evidence for such a mechanism from observations in conjoined twins. Wang and Skarsgard [2004] have report an interesting case of left-sided gastroschisis associated with abdominal and thoracic situs inversus. In their observation, intestinal non rotation was present in a mirror-image manner, with small bowel located on the left side of the abdomen and the colon on the right. Situs inversus is observed in one of the twins in approximately half of the cases of dicephali and thoracophagi conjoined twins. In this instance, it is mostly the right twin that is affected. In these twins, the right lateral plate mesoderm of the left embryo and the left lateral plate mesoderm of the right embryo are juxtaposed. Thus, asymmetric signalling pathways in each twin can influence the other, and this may result in randomization of situs [reviewed by Peeters and Devriendt, 2006]. It is not clear whether the mechanisms establishing left-right asymmetry of the internal organs as seen in heterotaxie can be related to the observed asymmetrical features described in mirror-image twins (see above). Moreover, in monozygotic twins, the splitting of the embryo occurs at a much earlier stage in development compared
T.K. Lubala et al. / European Journal of Medical Genetics 58 (2015) 266e269
to conjoined twins, and it is not known to what extent asymmetric signals are already established at that stage. The present observation of discordant, asymmetric position of the gastroschisis in these twins may therefore be an argument that gastroschisis is a primary malformation, with a developmental origin rather than a disruption. Conflicts of interest The authors did not have conflicts of interest. Author contributions Toni Kasole Lubala: Clinical examination and redaction of the manuscript. Sébastien Mbuyi-Musanzayi: Clinical examination and review of literature. Nina Lubala: Review of literature. Oscar Numbi Luboya: Clinical examination and patient management. Prosper Mwenze Kalenga: Correction of the manuscript. Koenraad Devriendt: Supervision and correction of the manuscript. Prosper Tshilobo Lukusa: Correction of the manuscript. Acknowledgements We thank the family of the patient for their kind cooperation. References Aknin C, Allart JF, Rouland JF. Unilateral keratoconus and mirror image in a pair of monozygotic twins. J Fr Ophtalmol 2007;30(9):899e902. Bradnock TJ, Marven S, Owen A, Johnson P, Kurinczuk JJ, Spark P, et al. Gastroschisis: one year outcomes from national cohort study. BMJ 2011;343:d6749. Brent B. Repair of microtia with sculpted rib cartilage grafts in identical, mirrorimage twins: a case study. Ann Plast Surg 2011;66(1):62e4. Bugge M, Petersen MB, Christensen MF. Monozygotic twins discordant for gastroschisis: case report and review of the literature of twins and familial occurrence of gastroschisis. Am J Med Genet 1994;52(2):223e6. Burke PH, Healy MJR. A serial study of normal facial asymmetry in monozygotic twins. Ann Hum Biol 1993;20:527e34. Cidis MB, Warshowsky JH, Goldrich SG, Meltzer CC. Mirror-image optic nerve dysplasia with associated anisometropia in identical twins. J Am Optom Assoc 1997;68(5):325e9. da Silva Dalben G, Dos Santos Souza MS, de Castro CH, Gonçalves M, Dos Santos CR, Consolaro A. Conjoined twins with mirror-image cleft lip and palate: case report in Brazil. Cleft Palate Craniofac J 2008;45(3):315e8. Deveer R, Engin-Ustun Y, Kale I, Aktulay A, Danisman N, Mollamahmutoglu L. Anencephalic conjoined twins with mirror-image cleft lip and palate. Clin Exp Obstet Gynecol 2010;37(3):231e2. deVries PA. The pathogenesis of gastroschisis and omphalocele. J Pediatr Surg 1980;15:245e51. Dirani M, Schache M, Baird PN. Mirror image congenital esotropia and concordant hypermetropia in identical twins. Eur J Ophthalmol 2009;19(6):1073e5.
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Djordjevic J, Jadallah M, Zhurov AI, Toma AM, Richmond S. Three-dimensional analysis of facial shape and symmetry in twins using laser surface scanning. Orthod Craniofac Res 2013;16(3):146e60. Feldkamp ML, Carey JC, Sadler TW. Development of Gastroschisis: review of hypotheses, a novel hypothesis and implications for research. Am J Med Genet A 2007;143:639e52. Goto T, Nemoto T, Okuma T, Kobayashi H, Funata N. Mirror-image solitary bone cyst of the humerus in a pair of mirror-image monozygotic twins. Arch Orthop Trauma Surg 2008;128(12):1403e6. Helland CA, Wester K. Monozygotic twins with mirror image cysts: indication of a genetic mechanism in arachnoid cysts? Neurology 2007;69(1):110e1. Hoyme HE, Higginbottom MC, Jones KL. The vascular pathogenesis of gastroschisis: intrauternine interruption of the omphalomesenteric artery. J Pediatr 1981;98: 228e31. Jones KL, Benirschke K, Chambers CD. Gastroschisis: etiology and developmental pathogenesis. Clin Genet 2009;75:322e5. Kim WK, Chung SA, Lee JB. Two cases of mirror-image eye anomalies in monozygotic twins. Korean J Ophthalmol 2010;24(5):314e7. Mandelia A, Agarwala S, Sharma N, Solanki S, Panda S. Left-sided gastroschisis: a rare congenital anomaly. JCDR 2013;7(10):2300. Newman HH. Studies of human twins II. Asymmetry reversal or mirror imaging in identical twins. Biol Bull 1928;55(4):298e315. Nik-Hussein NN, Salcedo AH. Double teeth with hypodontia in identical twins. ASDC J Dent Child 1987;54(3):179e81. Okamoto F, Nonoyama T, Hommura S. Mirror image myopic anisometropia in two pairs of monozygotic twins. Ophthalmologica 2001;215:435e8. Paranjothy S, Broughton H, Evans A, Huddart S, Drayton M, Jefferson R, et al. The role of maternal nutrition in the aetiology of gastroschisis: an incident casecontrol study. Int J Epidemiol 2012;41(4):1141e52. Peeters H, Devriendt K. Human laterality disorders. Eur J Med Genet 2006;49(5): 349e62. Polifka JE, Friedman JM. Clinical teratology: identifying risks in humans. Clin Genet 1999;56(6):409e20. Riess A, Dufke A, Riess O, Beck-Woedl S, Fode B, Skladny H, et al. Mirror-image asymmetry in monozygotic twins with Kabuki syndrome. Mol Syndromol 2012;3:94e7. Sarda P, Bard H. Gastroschisis in a case of dizygotic twins: the possible role of maternal alcohol consumption. Pediatrics 1984;74(1):94e6. Satoh K, Shibata Y, Tokushige H, Onizuka TA. Mirror image of the first and second branchial arch syndrome associated with cleft lip and palate in monozygotic twins. Br J Plast Surg 1995;48(8):601e5. Schultz AC, Stressig R, Ritgen J, Bagci S, Müller A, Gembruch U, et al. A classic twin study of isolated gastroschisis. Fetal Pediatr Pathol 2012;31(5):324e30. Song J, Song A, Shim A, Kim E, Song M. Mirror-image identical twins presenting in mirror-image hip cyst: a case report and review of the literature. Rheumatol Curr Res 2013;S17:2161. Sperber GH, Machin GA, Bamforth FJ. Mirror-image dental fusion and discordance in monozygotic twins. Am J Med Genet 1994;51(1):41e5. Stankovi c-Babi c G, Vujanovi c M, Ceki c S. Identical twins with “mirror image” anisometropia and esotropia. Srp Arh Celok Lek 2011;139(9e10):661e5. Torfs CP, Katz EA, Bateson Tf, Lam PK, Curry CJ. Maternal medications and environemental exposures as risk factors for Gastroschisis. Teratology 1996;54(2): 84e92. Valdéz JAL, Cóyotl DMC, Vega CAV. New embryological hypothesis, genetics and epidemiology of gastroschisis. Bol Med Hosp Infant Mex 2011;68(3):224e31. Wang KS, Skarsgard ED. Left-sided gastroschisis associated with situs inversus. J Pediatr Surg 2004;39(12):1883e4. Werler MM, Sheehan JE, Mitchell AA. Maternal medication use and risks of gastroschisis and small intestinal atresia. Am J Epidemiol 2002;155(1):26e31. Werler MM. Teratogen update: pseudoephedrine. Birth Defects Res A Clin Mol Teratol 2006;76(6):445e52. Zhou JY, Pu JL, Chen S, Hong Y, Ling CH, Zhang JM. Mirror-image arachnoid cysts in a pair of monozygotic twins: a case report and review of the literature. Int J Med Sci 2011;8(5):402e5.
Contents lists available at ScienceDirect
European Journal of Medical Genetics journal homepage: http://www.elsevier.com/locate/ejmg
Clinical report
Mirror-image gastroschisis in monochorionic female twins Toni Kasole Lubala a, Sébastien Mbuyi-Musanzayi b, Nina Lubala c, Oscar Numbi Luboya a, Prosper Muenze Kalenga d, Koenraad Devriendt e, *, Prosper Lukusa-Tshilobo e, f a
Department of Pediatrics, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo Department of Surgery, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo c Department of Ophthalmology, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo d Department of Gynecology and Obstetrics, University Hospital, University of Lubumbashi, P.O. 1825, Lubumbashi, Democratic Republic of the Congo e Center for Human Genetics, University Hospitals, KU Leuven, P.O. Box 602, 3000 Leuven, Belgium f Department of Pediatrics, University Hospitals, University of Kinshasa, P.O. Box 123, Kin XI, Kinshasa, Democratic Republic of the Congo b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 October 2014 Accepted 8 March 2015 Available online 14 March 2015
We report a case of “mirror-image” gastroschisis in female monochorionic twins. One of the twins presents a right-sided gastroschisis, the other a left-sided gastroschisis. Both twins have anteriorly placed anus and sacral dimple. To the best of our knowledge, this represents the first case of mirror image or discordant left and right gastroschisis in monochorionic twins reported in the literature. This observation may shed further light on the pathogenesis of gastroschisis. Ó 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Gastroschisis Left Right Sacral dimples Monochorionic twins
1. Introduction Gastroschisis is a herniation of abdominal content through a paramedian full-thickness abdominal defect [Jones et al., 2009]. During the past 30 years, its incidence has increased 10e20 fold worldwide, with clear regional variations [Bradnock et al., 2011; Valdèz et al., 2011]. The etiology of gastroschisis is still unclear. Five different theories have been proposed to explain the pathogenesis of this anomaly, but none of them is totally compatible with the current knowledge in human embryology [reviewed by Feldkamp et al., 2007; Valdèz et al., 2011]. Two main embryological hypothesis have been previously proposed: deVries [1980] suggested that abnormal involution of the right umbilical vein leads to adverse effects on the adjacent mesoderm, followed by the subsequent rupture of the body wall. In the second theory, Hoyme et al. [1981] suggest that gastroschisis results from an intrauterine interruption of the omphalomesenteric artery witch causes infarction and necrosis of the base of the umbilical cord, rupture of the body wall and intestinal herniation through the defect.
* Corresponding author. Tel.: þ32 16 34 59 03; fax: þ32 16 34 60 60. E-mail address: [email protected] (K. Devriendt). http://dx.doi.org/10.1016/j.ejmg.2015.03.001 1769-7212/Ó 2015 Elsevier Masson SAS. All rights reserved.
More recently, Feldkamp et al. [2007] suggested that gastroschisis could be considered as a ventral body wall malformation rather than a vascular disruption. Right-sided gastroschisis is the most common form, the leftsided one being exceptional. In fact, only about 20 cases of leftsided gastroschisis were reported from 1988 to 2010 [Mandelia et al., 2013]. We report monochorionic female twins who both presented at birth a gastroschisis, but discordant regarding the right/left sided location. 2. Clinical report Diamniotic monochorionic female twins were vaginally born at term and referred to us on day three for gastroschisis. The parents are not consanguineous, the father was 28 years old, the mother 19 years. They had an elder brother, alive and healthy. Family history is negative with regard to congenital malformations. The mother denied substance abuse (alcohol or tobacco) and there were no infections during pregnancy. However, the mother did not have any prenatal consultation during pregnancy nor did she receive the required periconceptional folic acid supplementation. On clinical examination, both twins were small for date, with weight 1900 g (2, 7 SD e CDC growth chart), length 49 cm (P50) and head circumference 35 cm (P50). There was no facial
T.K. Lubala et al. / European Journal of Medical Genetics 58 (2015) 266e269
dysmorphism. A large abdominal wall defect was noted in both twins (Fig. 1). In the first twin, the abdominal wall defect was situated on the right side, 2 cm from an intact umbilical cord and there was a herniation of the liver together with oedematous and thickened small bowel loops. In the second twin, the defect was left-sided, about 2.5 cm from the umbilical cord with evisceration of oedematous small bowel loops. The clinical examination also revealed an anteriorly placed anus (Fig. 2). A lumbosacral dimple was observed in both of them, possibly indicating an underlying lumbosacral spine defect. No radiographs could be obtained (Fig. 3). They died on day 4 and day 6, respectively, before any surgery could be performed because they were in a very poor medical condition, with already seriously affected small bowel. 3. Discussion We here report the unique observations of female monochorionic twins who were concordant for a gastroschisis, but discordant regarding the left or right sided position. Whereas in one twin the defect was right sided, as most commonly seen, in the other it was on the left side, which is exceptional. Thus the monochorionic twins presented a “mirror-image” gastroschisis. This observation may shed light on the pathogenesis of gastroschisis. Currently, the exact etiology of gastroschisis is not well understood. The first report of a gastroschisis in twins reported a male and female dizygotic twins concordant for a right-sided gastroschisis [Sarda and Bard, 1984]. More recently, Bugge et al. described for the first time a pair of monozygotic female twins discordant for a right-sided gastroschisis [Bugge et al., 1994]. In a twin study, Schultz et al. [2012] found that the concordance rate was not significantly different amongst dizygotic twins (4 out of 8 twins) compared to monozygotic twins (2 out of 5 twins reported). If we include our case with concordant gastroschisis, 3 out of 6 monozygotic twins are concordant, which is equal the concordance observed in dizygotic twins. However, it should be noted that the number of reported twins with gastroschisis is very small so we cannot evaluate the relative contribution of genetic versus environmental factors. One of the non-genetic factors identified is young maternal age, with an increased risk (7
267
times) for the mothers between the ages 14 and 19. In our case, the young maternal age (19 years) might have contributed to the gastroschisis [Valdéz et al., 2011]. How young maternal age may influence the risk is not known, but some studies reported an association with life-style factors, e.g. consuming alcohol, cocaïne and tobacco [Polifka and Friedman, 1999], medication such as misoprostol and cyclooxygenase inhibitors like aspirin and Ibuprofen and pseudoephedrine during pregnancy. [Polifka and Friedman, 1999; Werler, 2006; Werler et al., 2002]. The world-wide increase in incidence of gastroschisis during the last ten years may be related to unknown risk factors related to the lifestyle in young mothers. This association with vasoactive agents supports a vascular disruption pathogenesis, at least in a subset of cases [Torfs et al., 1996]. A vascular disruption would also explain the frequent association of gastroschisis with intestinal atresia and stenosis, also thought to have a vascular disruption origin [Werler et al., 2002]. There was no history of exposure to any of these substances in our case. However, the mother did not receive periconceptional folic acid supplementation. Some authors consider this supplementation as having a protective effect [Paranjothy et al., 2012]. Beside those non-genetic factors, a multifactorial origin of gastroschisis is suggested by the existence of familial cases, with an empiric recurrent risk of 3, 5%, and the observed positive association between gastroschisis and variants in genes linked to angiogenesis [Feldkamp et al., 2007]. Feldkamp et al. [2007] suggested an unifying hypothesis on the origin of most ventral wall defects, including gastroschisis, cloacal exstrophy or ectopia cordis. These authors furthermore suggested that the different processes that impact ventral wall closure might also contribute to neural tube closure [Feldkamp et al., 2007]. This could explain the concomitant presence of gastroschisis and sacral dimples in both monozygotic twins in our observation. One intriguing observation is the “mirror-image” position of the gastroschisis in these monochorionic twins. This has not been reported before. Several monozygotic twins have been reported with mirror-image unilateral malformations in other organs or regions of the body (see Table 1). This may suggest a pathogenic
Fig. 1. (A) large anterior abdominal wall defect on patient’s the right side of the umbilical cord with an eviscerated, oedematous and thickened liver and part of the small bowel loops for the first twin. (B) In the second twin, the abdominal wall defect was on patient’s left side of the umbilical cord with eviscerated and oedematous small bowel loops.
268
T.K. Lubala et al. / European Journal of Medical Genetics 58 (2015) 266e269
Fig. 2. Anteriorly placed position of the anus in both twins.
Fig. 3. Sacral dimples in both twins.
relationship between mirror-image asymmetry and the process of twinning. However, one has to be cautious, since these are all single case reports, and therefore, it is not excluded that the concept of mirrorimage of malformations in monozygotic twins are chance observations and that the case reports represent an ascertainment and Table 1 Overview of reported mirror-image anomalies reported in monozygotic twins. Affected system
Defect
Nervous Arachnoid cyst system Arachnoid cyst Eye Optic nerve hypoplasia Myopic anisometropia Unilateral keratoconus Esotropia Lacrymal fistula Myopic anisometropia Esotropia Ear Microtia Orofacial Double teeth with hypodontia Mandibular incisor/canine fusion Cleft lip/palate Cleft lip/palate Cleft lip/palate Clefs lip/palate Hip cysts Limbs Solitary bone cyst of the humerus
Country
Study
Year
Norway China USA Japan France Australia Turkey Korea Serbia USA Malaysia
2007 2011 1997 2001 2007 2009 2010 2010 2011 2011 1987
Canada
Helland and Wester Zhou et al. Cidis et al. Okamoto et al. Aknin et al. Dirani et al. Deveer et al. Kim et al. Stankovi c-Babi c et al. Brent Nik-Hussein and Salcedo Sperber et al.
1994
Japan Brazil Turkey Germany USA Japan
Satoh et al. da Silva et al. Deveer et al. Reiss et al. Song et al. Goto et al.
1995 2008 2010 2012 2013 2008
publication bias. In accordance with this, no higher degree of facial asymmetry was observed in monozygotic twins compared to dizygotic twins [Burke and Healy, 1993; Djordjevic et al., 2013]. On the other hand, in the only systematic twin study we were able to ascertain, a discordance in the clockwise or counterclockwise direction of crown whorl of the head hair was much higher in identical (15/47) than in fraternal twins (5/48) [Newman, 1928]. This suggests that the process of twinning is associated with disturbance of a mechanism establishing (a) symmetry. Alternatively, an underlying defect in establishing (a) symmetry may be at the basis of the twinning process. There is evidence for such a mechanism from observations in conjoined twins. Wang and Skarsgard [2004] have report an interesting case of left-sided gastroschisis associated with abdominal and thoracic situs inversus. In their observation, intestinal non rotation was present in a mirror-image manner, with small bowel located on the left side of the abdomen and the colon on the right. Situs inversus is observed in one of the twins in approximately half of the cases of dicephali and thoracophagi conjoined twins. In this instance, it is mostly the right twin that is affected. In these twins, the right lateral plate mesoderm of the left embryo and the left lateral plate mesoderm of the right embryo are juxtaposed. Thus, asymmetric signalling pathways in each twin can influence the other, and this may result in randomization of situs [reviewed by Peeters and Devriendt, 2006]. It is not clear whether the mechanisms establishing left-right asymmetry of the internal organs as seen in heterotaxie can be related to the observed asymmetrical features described in mirror-image twins (see above). Moreover, in monozygotic twins, the splitting of the embryo occurs at a much earlier stage in development compared
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to conjoined twins, and it is not known to what extent asymmetric signals are already established at that stage. The present observation of discordant, asymmetric position of the gastroschisis in these twins may therefore be an argument that gastroschisis is a primary malformation, with a developmental origin rather than a disruption. Conflicts of interest The authors did not have conflicts of interest. Author contributions Toni Kasole Lubala: Clinical examination and redaction of the manuscript. Sébastien Mbuyi-Musanzayi: Clinical examination and review of literature. Nina Lubala: Review of literature. Oscar Numbi Luboya: Clinical examination and patient management. Prosper Mwenze Kalenga: Correction of the manuscript. Koenraad Devriendt: Supervision and correction of the manuscript. Prosper Tshilobo Lukusa: Correction of the manuscript. Acknowledgements We thank the family of the patient for their kind cooperation. References Aknin C, Allart JF, Rouland JF. Unilateral keratoconus and mirror image in a pair of monozygotic twins. J Fr Ophtalmol 2007;30(9):899e902. Bradnock TJ, Marven S, Owen A, Johnson P, Kurinczuk JJ, Spark P, et al. Gastroschisis: one year outcomes from national cohort study. BMJ 2011;343:d6749. Brent B. Repair of microtia with sculpted rib cartilage grafts in identical, mirrorimage twins: a case study. Ann Plast Surg 2011;66(1):62e4. Bugge M, Petersen MB, Christensen MF. Monozygotic twins discordant for gastroschisis: case report and review of the literature of twins and familial occurrence of gastroschisis. Am J Med Genet 1994;52(2):223e6. Burke PH, Healy MJR. A serial study of normal facial asymmetry in monozygotic twins. Ann Hum Biol 1993;20:527e34. Cidis MB, Warshowsky JH, Goldrich SG, Meltzer CC. Mirror-image optic nerve dysplasia with associated anisometropia in identical twins. J Am Optom Assoc 1997;68(5):325e9. da Silva Dalben G, Dos Santos Souza MS, de Castro CH, Gonçalves M, Dos Santos CR, Consolaro A. Conjoined twins with mirror-image cleft lip and palate: case report in Brazil. Cleft Palate Craniofac J 2008;45(3):315e8. Deveer R, Engin-Ustun Y, Kale I, Aktulay A, Danisman N, Mollamahmutoglu L. Anencephalic conjoined twins with mirror-image cleft lip and palate. Clin Exp Obstet Gynecol 2010;37(3):231e2. deVries PA. The pathogenesis of gastroschisis and omphalocele. J Pediatr Surg 1980;15:245e51. Dirani M, Schache M, Baird PN. Mirror image congenital esotropia and concordant hypermetropia in identical twins. Eur J Ophthalmol 2009;19(6):1073e5.
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