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ORIGINAL ARTICLE
Year : 2002  |  Volume : 18  |  Issue : 2  |  Page : 111-116
 

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome - a review


Department of Urology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
N P Gupta
Department of Urology, All India Institute of Medical Sciences, New Delhi - 110 029
India
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   Abstract 

Purpose: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital malformation characterized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract butfunc­tional ovaries. We review the embryological, endocrino­logical, clinical, diagnostic, psychosocial and therapeutic features of this syndrome.
Material and Methods: We performed a computer­ised Medline search and manual bibliographical review of more than 100 relevant articles on MRKHS published in the last 25 years. A thorough analysis of embryo­logical, endocrinological, clinical, psychosocial, diag­nostic and therapeutic features of this syndrome was performed and the important findings are summarised.
Results: Embryologically, MRKHS appears to be the result of non fusion of the mesonephric duct (MD) with the Wolff an (WD). The various Mullerian defects found are agenesis of vagina or uterus, rudimentary vagina or uterus with normal ovarian function. Nearly 50% of these patients have renal anomalies like renal agenesis, ectopic kidney, fusion anomaly like horse-shoe kidney and vesicoureteric reflux. Skeletal abnormalities are found in 10% of these patients, 2/3 of whom have anoma­lies of the spine, ribs or limbs. Clinical observations also support the view that 2 or more syndromes lie behind the title of MRKH syndrome, namely an isolated form of con­genital agenesis of the vagina and uterus (typical/type A) and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even an obligatory characteristic (atypical/type B).
Conclusion: Mayer-Rokitansky-Kuster-Hauser syn­drome (MRKHS) is a congenital malformation charac­terized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract but functional ovaries. The various urinary tract anomalies described are renal agenesis, pelvic kidney, fusion anomaly like horse-shoe kidney and vesicoureteric reflux. It is not only worthwhile to be alert for these anomalies but also to study the skeletal and auditory systems in these pa­tients. The technology of in vitro fertilization enables a woman without a uterus to have her own genetic children.


Keywords: Mayer-Rokitansky-Kuster-Hauser Syndrome; Mullerian Defects; Urinary Tract Anomalies


How to cite this article:
Gupta N P, Ansari M S. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome - a review. Indian J Urol 2002;18:111-6

How to cite this URL:
Gupta N P, Ansari M S. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome - a review. Indian J Urol [serial online] 2002 [cited 2019 Jul 22];18:111-6. Available from: http://www.indianjurol.com/text.asp?2002/18/2/111/37398



   Introduction Top


Agenesis of the vagina in karyotypic female subjects may be accompanied by other defects of the urogenital and skel­etal system. The combination of these anomalies has been designated as Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) based on the findings reported by the various authors. We performed a computerised Medline search and manual bibliographical review of more than 100 relevant articles on MRKHS and the embryological, endocrinological, clinical, psychosocial, diagnostic and therapeutic features of this syndrome are discussed.


   Embryology Top


Griffin (1988), described the embryological possibilities for the origin of MRKH syndrome. The Mullerian duct (MD; ductus paramesonephricus) develops independent of the coelomic epithelium above the mesonephros. This part of the duct gives rise to the infundibulum with its fimbriated ostium abdominale. The part of the duct which lies along the mesonephros as far as its caudal pole makes a contribu­tion to the ampulla and less often to the isthmus. In the area of the mesonephros the MD fuses with the Wolffian duct (WD; ductus mesonephricus). The WD gives rise to the ampulla and the isthmus. Below the caudal pole of the mes­onephros, as well as beyond the attachment point of the in­guinal ligament of the mesonephros, the later round ligament of the uterus, the MD develops as an outgrowth of the WD and no longer as an independent structure. The MRKH syn­drome is, in its formal genesis, a non-fusion of the MD with the WD. This explains the fact that in a classic case of MRKH syndrome, the  Fallopian tube More Details with a very small part of the cornu uteri extends only as far as the connection with the round ligament of the uterus. It is suggested that the cause of the development of MRKH syndrome could be a deficiency of gestagen and/or oestrogen receptors. This would also explain the various forms of the rudimentary vagina. [1] Ghirardini et al (1982), described etiopathogene­tical problems in MRKH syndrome, supporting Hauser's hypothesis of an inhibition of the mullerian duct develop­ment by MIF production, allowing it to consider it as the slightest form of female pseudohermaphroditism. Moreover the terms used to delineate this condition, like "mullerian aplasia", "mullerian duct aplasia", "mullerian duct agen­esis" and "uterovaginal agenesis" may be misleading and the term of "mullerian dysgenesis syndrome" is proposed.' [2]


   Genetics and Molecular Basis of MRKHS Top


Pavanello et al (1988) stated that genetic problems are interwoven with unilateral or bilateral renal agenesis, es­pecially that associated with mullerian anomalies as seen in MRKH syndrome. The gene is single and autosomal dominant with variable expression. [3] Ghirardini et al (1982), described the histological appearance of the rudimentary uterus, endometrium, uterine tube, Gartner's duct, round ligament, vagina and ovary in 10 cases of the MRKH syn­drome. Their findings suggested that this syndrome is due to a deficiency of the oestrogen and gestagen receptors. This deficiency may inhibit the further development of the embryonic mullerian duct and account for the subse­quent faulty differentiation of its existing elements. It is still undecided why, in cases of the MRKH syndrome, development of the mullerian duct ceases at the attach­ment of the caudal mesonephric ligament (later the round ligament). [4] Cramer et al (1996), reported that vaginal agen­esis might be associated with decreased activity of galac­tose-l-phosphate uridyl transferase (GALT). They studied activity and genotype of GALT in 13 daughters with vagi­nal agenesis and their mothers. They concluded that fetal or maternal GALT mutations that decrease GALT activity may be associated with vaginal agenesis and have, as their possible biological basis, increased intrauterine exposure to galactose which has been demonstrated in rodents to cause decreased oocyte survival and delayed vaginal open­ing in offspring. [5]


   Review of Literature Top


Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome is a congenital malformation characterized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract but functional ovaries. In 1829 Mayer had described partial and complete duplica­tion of vagina in 4 stillborns along with other anomalies like cleft lip, limb and cardiac defects along with urinary tract anomalies. [6] Subsequently in 1838, Rokitansky re­ported 19 cases of uterovaginal agenesis along with renal agenesis in three cases. [7] Kuster (1910), described several cases of similar anomaly with various musculoskeletal defects. Hauser et al (1961), emphasized the importance of distinguishing this syndrome from that of testicular feminisation in both of which vaginal development is de­fective. [8] The various mullerian defects described are agen­esis of vagina or uterus, rudimentary/atretic vagina or uterus. Unilateral renal and skeletal anomalies are associ­ated in 50% and 12% of cases, respectively. [9] The skeletal abnormalities reported are fusion anomaly of vertebrae, congenital scoliosis, and limb deformities like brachy­mesophalangy of digits, small distal phalanx of digits, long proximal phalanx of digits, and long metacarpals of dig­its. In addition, some patients might have distinct radial dysplasia and abnormalities of the carpals. [10] It has been analysed whether the MRKH syndrome can be consid­ered as a single clinical entity or whether two or more syndromes lie behind the title of MRKH syndrome. Two different syndromes in these patients have been described, namely an isolated form of congenital agenesis of the va­gina and uterus (typical) and a more generalized condi­tion, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic (atypical). Heidenreich et al (1988), observed that the patients with the Mayer-Rokitansky-Kuster (MRK) syndrome had the typical findings of vaginal aplasia and bipartite solid uter­ine buds. Among the other 23 patients, 15 had additional malformations of the kidneys and urinary tract. 8 patients had more or less marked skeletal malformations, especially of the cervical vertebrae. So, they proposed that the term "MRKH syndrome" should no longer be used for such cases with extragenital malformations. [11] Strubbe (1992), described that the typical form (type A) is characterized by symmetrical nonfunctioning muscular buds (the Mul­lerian duct remnants) and normal fallopian tubes, and the atypical form by aplasia of one or both buds, one bud smaller than the contralateral one, with or without dyspla­sia of one or both fallopian tubes. Radiographs of the spine showed that congenital spinal abnormalities, especially the Klippel-Feil (KF) syndrome, were seen more in patients with the typical form. Renal agenesis or ectopia together with the MRKH and KF syndromes, known as the MURCS association (MU: Mullerian duct aplasia; R:renal agen­esis/ectopia; CS:cervical somite dysplasia), was also di­agnosed in patients in the atypical group. From their results, they concluded that additional cervical spine films in pa­tients with the MRKH syndrome are indicated only in the atypical form of the syndrome. In those cases, where the MRKH syndrome is associated with the KF syndrome, the MURCS association should be considered. [12] Strubbe et al (1994) conducted a multidisciplinary study on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. The purpose of this study was to discriminate typical (type A) from atypical (type B) Mayer-Rokitansky­Kuster-Hauser syndrome (congenital absence of vagina and uterus) and determine their association with renal anomalies and ovarian disease. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data; a typical and an atypical form of the MRKH syndrome. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an iso­lated form of congenital agenesis of the vagina and uterus (typical/type A) and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic (atypical/type B). Hence they proposed that the term MRKH syndrome should no Longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome. [13] Strubbe et al (1993), emphasised that discrimination between type A and type B of MRKH syndrome is important because associated renal and ovar­ian abnormalities occur only in type B. Laparoscopy is still neeeded to discriminate between these two forms. [22] We also describe 5 cases of MRKH syndrome that nearly exemplify all types of renal anomalies described, includ­ing one with fusion anomalies of vertebrae and ectopic ureter with urinary incontinence [Table - 1]. This rare combination of MRKH syndrome and ectopic ureter with uri­nary incontinence has not been described previously in the literature to the best of our knowledge.


   Urinary Tract Anomalies in MRKHS Top


Unilateral renal anomalies are associated with 50% of the patients. The various urinary tract anomalies reported are renal agenesis, pelvic kidney, fusion anomaly like horse-shoe kidney and vesicoureteric reflux. We describe 5 cases of MRKHS [Table - 1] [Figure - 1],[Figure - 2],[Figure - 3],[Figure - 4], which exemplify most of the urinary tract anomalies, including one associ­ated with ectopic ureter with urinary incontinence, a com­bination that has not been described in the literature so far . [27]


   Classification of Mullerian Defects Top


Many investigators have classified mullerian defects but the most comprehensive classification appears to be pro­posed by Tarry and Duckett (1986), which is based on physical and ultrasound examinations or laparoscopy, and prognostic implications regarding fertility and menstrua­tion. [15] The grade 0-4 refer to the extent of mullerian sys­tem affected. Each side is graded individually. The letter M refers to mullerian defects. Fortuitously, the M stands for Mayer-Rokitansky as well. The grading is described as follows:

MO-unilateral system normally formed but unfused or septum retained,

M1-vaginal agenesis alone,

M2-vaginal and uterine agenesis.

M3-mullerian agenesis total, and

M4-mullerian and ovarian agenesis.


   Endocrine Function in MRKHS Top


In most of the cases, both ovaries are normal and af­fected women have "normal" sexual activity. Occasion­ally one ovary with ipsilateral fallopian tube may be absent. Hormone profile and secondary sexual characteristics are normal in the cases of Mayer-Rokitansky-Kuster-Hauser syndrome. [16]


   Karyotype and Familial Syndrome Top


Smith et al (1982), reported that patients with MRKH have a normal female karyotype and normal secondary sexual development. [17] Cabra el (1998), and Orozco­Sanchez et al (1991), performed blood genetics tests plus biopsy of ovarian tissue which showed 46 XX karyotype with no structural anomalies. [18],[19] Smith used the appella­tion "Rokitansky malformation Sequence" to designate the mullerian agenesis in any clinical setting and stated that about 4% of the cases in which ovaries and fallopian tubes are present but which lack the body of the uterus and up­per vagina are familial with affected female siblings. [17]


   Other Syndromes and Anomalies in Association to MRKHS Top


The various other associated anomalies reported are  Klippel-Feil syndrome More Details, Sprengel's deformity, and congeni­tal stapedial ankylosis and ovarian cysts. [20]


   Investigations Top


These tests included general physical examination, radio­graphs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryn­gologieal and ossicular chain examinations. Ultrasound (US) of the abdomen and pelvis, which might show a dilated uterus with hematometra, the lesion with functioning uter­ine anlage, cervical dysgenesis and an obstructed uterine horn besides the delineation of kidneys and ovaries. Many investigators feel that transabdominal ultrasound (US) may not provide a completely reliable picture in Mullerian duct anomalies. Hence, magnetic resonance imaging (MRI) is now gaining wide acceptance in imaging congenital abnor­malities of the genital tract. [21] Genitography can further pro­vide anatomical details specially in cases of partial vaginal agenesis or coexistent genitourinary fistula.


   Management Top


The management of vaginal agenesis in Mayer-Roki­tanksy-Kuster-Hauser syndrome has always been a con­troversial topic. The choice of procedure and patient age at reconstruction depend upon individual anatomy, fertil­ity potential and psychological and social factors. Initially, the arguments centered on whether to do surgery or try passive dilation as well as at what age to intervene. As surgical techniques have recently become refined, the question is, if surgery is selected, what type of tissue should one use (bowel vs. skin graft) and, if skin graft, from what area to select. The aims are satisfactory sexual activity with good anatomical and functional vagina along with mechanical long-term outcomes. Until now, the recom­mended treatment, when resection of a rudimentary horn was indicated, was laparotomy. The same goal can now be achieved by laparoscopy. Laparoscopy is not only use­ful for diagnosis of uterine malformations but can also be valuable for any treatment required for this type of mal­formation along with creation of an artificial vagina (laparoscopic assisted vaginoplasty).[22],[23]


   Psychological Aspect Top


Patients with MRKH syndrome might suffer from se­vere distortions of body image, anxiety, depression, inter­personal sensitivity and face a lot of psychological distress at diagnosis. Langer et al (1990), studied psychosocial sequelae of and coping with malformation and treatment with semistructured interviews and the Giessen test. Ana­tomical and functional results of the vaginoplastic opera­tion were excellent, and sexual satisfaction correlated with coping. 7/11 MRKH patients were capable of good to fair adaptation to the malformation. The malformation caused narcissistic damage in all cases. [24] Behavioral problems of the adolescent patients can be avoided by early appropri­ate guidance and reassurance.


   Can a Woman with MRKHS with Absent Uterus have a Child? Its Medicolegal Implications Top


Until recently, treatment for patients with vaginal agen­esis (Mayer-Rokitansky-Kuster-Hauser syndrome) has centered on the creation of a functional vagina. The tech­nology of in vitro fertilization and embryo transfer, al­lowing for collection of oocytes from the genetic mother. fertilization by the genetic father, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic child. The specific medical and le­gal issues involved in facilitating genetic offspring in these instances must be considered; these include the initial matching of the genetic parents with the gestational car­rier, cycle synchronization for in vitro fertilization and embryo transfer, anatomic difficulties of oocyte retrieval. birth certificate documentation, and the current legal sta­tus of a gestational carrier. [25],[26]


   Conclusion Top


Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is a congenital malformation characterized by an absence of the vagina associated with a variable abnormality of the uterus and the urinary tract but functional ovaries. It is not only worthwhile to be alert for urinary tract anomalies in patients with the MRKH syndrome, but also to study the skeletal and auditory systems in these patients. Psy­chological consideration of patients with uterovaginal agenesis may dictate the need for early vaginoplasty, which hitherto has been delayed until just before marriage. Sur­gical correction many a times require the creation of a neovaginal canal by the performance of a neovaginoplasty which can be done by open surgical or laparoscopic as­sisted techniques. The technology of in vitro fertilization and embryo transfer, allowing for collection of oocytes from the genetic mother, fertilization by the genetic fa­ther, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic children.

 
   References Top

1.Griffin JE, Edward C, Maddan JD. Harrod MJ, Wilsen JD. Con­genital absence of the vagina : The Mayer-Rokitansky-Kuster­Hauser syndrome. Ann Int Med 1976; 85: 224.  Back to cited text no. 1    
2.Ghirardini G, Segre A. Vaginal agenesis (Mayer-Rokitan sky- Kuster­Hauser syndrome) : recent etiopathogenetical and anatomical views. Clin Exp Obstet Gynecol 1982; 9: 98-102.  Back to cited text no. 2    
3.Pavanello RC, Eigier A, Otto PA. Relationship between Mayer­Rokitansky-Kuster anomaly and hereditary renal dysplasia (HRA). Am J Med Genet 1988; 29: 845.  Back to cited text no. 3    
4.Ludwig KS. The Mayer-Rokitansky-Kuster syndrome. An analy­sis of its morphology and embryology. Part I : Morphology. Arch Gynecol Obstet 1998; 262: 1-26.  Back to cited text no. 4    
5.Cramer DW, Goldstein DP, Fraer C. Reichardt JK. Vaginal agen­esis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the N3 14D mutation of galactose-l-phosphate uridyl transferase (GALT). Mol Hum Reprod 1996; 2: 145-148.  Back to cited text no. 5    
6.Mayer CAJ. Uber Verdopplungen des Uterus and ihre Arten, nebst Bemerkungen Uber hasensharte auf wolfsrachen. J Chir Auger 1989; 13: 525.  Back to cited text no. 6    
7.Rokitansky K. Uber die sogenennten Verdopplungen des uterus. Med Jahrb Ost Staat 1838; 26: 39.  Back to cited text no. 7    
8.Hauser GA, Schreiner WE. Mayer-Rokitansky-Kuster syndrome. Rudimentary solid bipartite uterus with solid vagina. Schweiz Med Wschr 1961; 91: 381.  Back to cited text no. 8    
9.Rosenberg HK, Sherman NH, Tarry WF, Duckett JW, Snyder HM. Mayer-Rokitansky-Kuster-Hauser syndrome : US aid to diagnosis. Radiology 1986; 161: 815-819.  Back to cited text no. 9    
10.Fisher K, Esham RH, Thorneycroft I. Scoliosis associated with typi­cal Mayer-Rokitansky-Kuster-Hauser syndrome. South Med J 2000; 93: 243-246.  Back to cited text no. 10    
11.Heidenreich W. Genital and extragenital abnormalities in Mayer­Rokitansky-Kuster syndrome. Dtsch Med Wochenschr 1988; 113: 1092-1096.  Back to cited text no. 11    
12.Strubbe EH, Lemmens JA, Thijn CJ, Willemsen WN, van Toor BS. Spinal abnormalities and the atypical form of the Mayer-Rokitansky­Kuster-Hauser syndrome. Skeletal Radiol 1992; 21: 459-462.  Back to cited text no. 12    
13.Strubbe EH, Cremers CW, Willemsen WN, Rolland R, Thijn CJ. The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome with­out and with associated features: two separate entities ? Clin Dysmorphol 1994; 3; 192-199.  Back to cited text no. 13    
14.Strubbe EH, Willemsen WN, Lemmens JA, Thijn CJ, Rolland R. Mayer-Rokitansky-Kuster-Hauser syndrome : distinction between two forms based on excretory, urographic, sonographic, and laparo­scopic findings. Am J Roentgenol 1993; 160: 331-334.  Back to cited text no. 14    
15.Tarry WE, Duckett JW, Stephens FD. The Mayer-Rokintansky Syn­drome : pathogenesis, classification and management. J Urol 1986; 136: 648-652.  Back to cited text no. 15    
16.Orozco-Sanchez J, Neri-Vela R, Flores-Mendez MS, Sandoval­Sevilla SF. Leon-Cordova K. Congenital atresia of the vagina. Bol Med Hosp Infant Mex 1991; 48: 648-655.  Back to cited text no. 16    
17.Smith DW. Recognizable pattern of human malformation. In : Ma­jor problems in clinical paediatrics. Genetic. Embryologic and Clini­cal aspects, 3rd ed., Philadelphia, Saunders. 1982; 7: 482.  Back to cited text no. 17    
18.Cabra Zurita R, Munuzuri F, Benitez EA, Barroso G. Congenital absence of the vagina. Mayer-Rokitansky-Kuster-Hauser syndrome. Presentation of a case and review of the literature. Gynecol Obstet Mex 1998; 66: 354-357.  Back to cited text no. 18    
19.Orozco-Sanchez J, Neri-Vela R, Flores-Mendez MS, Sandoval­Sevilla SF, Leon-Cordova K. Congenital atresia of the vagina. Bol Med Hosp Infant Mex 1991; 48: 648-655.  Back to cited text no. 19    
20.Cremers CW, Stnibbe EH, Willemsen WN. Stapedial ankylosis in the Mayer-Rokitansky-Kuster-Hauser syndrome. Arch Otolaryngol Head Neck Surg 1995; 121: 800-803.  Back to cited text no. 20    
21.Lang IM. Babyn P. Oliver GD. MR imaging of paediatric uterov­aginal anomalies. Pediatr Radio] 1999; 29: 163-170.  Back to cited text no. 21    
22.Otaa H, TanakaJi, Murakami M, Murata M, Fukuda J et al. Laparo­scopy-assisted Rule procedure for the creation of a neovagina in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 2000; 73: 641-644.  Back to cited text no. 22    
23.Chatwani A, Nyirjesy P, Harmanli OH, Grody MH. Creation of neovagina by laparoscopic Vecchietti operation. J Laparoendosc Adv Surg Tech A 1999; 9: 425-427.  Back to cited text no. 23    
24.Langer M. Grunberger W, Ringler M. Vaginal agenesis and con­genital adrenal hyperplasia. Psychosocial sequelae of diagnosis and neovagina formation. Acta Obstet Gynecol Scand 1990; 69: 343-­349.  Back to cited text no. 24    
25.Batzer FR, Corson SL, Gocial et al. Genetic offspring in patients with vaginal agenesis: specific medical and legal issues. Am J Obstet Gynecol 1992; 167: 1288-1292.  Back to cited text no. 25    
26.Egarter C, Huber J. Successful stimulation and retrieval of oocytes in patient with Mayer-Rokitansky-Kuster syndrome. Lancet 1988; 1283.  Back to cited text no. 26    
27.Gupta NP, Ansari MS, Nabi G. Ectopic ureter with urinary inconti­nence. A new variant of Mayer-Rokitansky-Kuster-Hauser syn­drome. Submitted for publication to International Urogynaecology Journal and Pelvic Floor Dysfunction.  Back to cited text no. 27    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
 
 
    Tables

  [Table - 1]

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    Abstract
    Introduction
    Embryology
    Genetics and Mol...
    Review of Literature
    Urinary Tract An...
    Classification o...
    Endocrine Functi...
    Karyotype and Fa...
    Other Syndromes ...
    Investigations
    Management
    Psychological Aspect
    Can a Woman with...
    Conclusion
    References
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