Zusammenfassung
Das Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrom ist durch das kongenitale Fehlen von Uterus und oberem Vaginalanteil charakterisiert, was auf eine embryonale Entwicklungsstörung der Müller-Gänge zurückzuführen ist. Die Kombination des MRKH Syndroms mit renalen und zervikothorakalen Fehlbildungen wird als MURCS-Assoziation bezeichnet. Die Ätiologie ist unklar. Wir stellen dieses Krankheitsbild anhand des Fallberichts einer 16-jährigen Patientin vor, die zusätzlich zu den Leitsymptomen der MURCS-Assoziation eine persistierende linke Vena cava superior und einen Vorhofseptumdefekt, eine Lippen-Kiefer-Gaumenspalte und Handfehlbildungen aufwies. Fluoreszenz-in-situ-Hybridisierung (FISH) zeigte im vorliegenden Fall keine größeren Deletionen oder Duplikationen der DiGeorge/VCFS (velocardiofacial syndrome) Region auf Chromosom 22q11.1 sowie der TBX5/TBX3 Region auf Chromosom 12q24.1. Die Sequenzierung des TP63L (p63) Gens auf Chromosom 3q27 blieb ebenfalls unauffällig. Unsere Untersuchungen liefern somit weitere Hinweise für die genetische Heterogenität der MURCS-Assoziation.
Summary
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by the congenital absence of uterus and upper part of the vagina as a result of Mullerian duct agenesis. The combination of MRKH syndrome with renal anomalies and cervicothoracic dysplasia is known as MURCS association (Mullerian aplasia, Renal anomalies, and Cervicothoracic Somite dysplasia). The etiology remains poorly understood. We delineate this disease by reporting on a 16-year-old patient showing the cardinal features of MURCS association accompanied by a persistent left superior vena cava and atrial septal defect, orofacial clefting, and mild reduction deformities of the left hand. Fluorescence in situ hybridization did not show major deletions or duplications of the DiGeorge/VCFS (velocardiofacial syndrome) region at chromosome 22q11.1 as well as the TBX5/TBX3 region at 12q24.1. In addition, sequencing of the TP63L (p63) gene, residing at 3q27, remained normal in the presented patient. Thus, we provide further evidence for the genetic heterogeneity of MURCS association.
References
Strübbe EH, Willemsen WNP, Lemmens JAM, Thijn CJP, Rolland R (1993) Mayer-Rokitansky-Küster-Hauser Syndrome: Distinction between two forms based on excretory urographic, sonographic, and laparoscopic findings. AJR 160: 331–334
Duncan PA, Shapiro LR, Stangel LR, Klein RA, Addonizio JC (1979) The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J Pediatr 95: 399–402
Pittock ST, Babovic-Vuksanovic D, Lteif A (2005) Mayer-Rokitansky-Kuster-Hauser anomaly and its associated malformations. Am J Med Genet 135A: 314–316
Bendavid C, Pasquier L, Watrin T, Morcel K, Lucas J, Gicquel I, et al (2007) Phenotypic variability of a 4q34-->qter inherited deletion: MRKH syndrome in the daughter, cardiac defect and Fallopian tube cancer in the mother. Eur J Med Genet 50: 66–72
Cheroki C, Krepischi-Santos AC, Szuhai K, Brenner V, Kim CA, Otto PA, et al (2008) Genomic imbalances associated with mullerian aplasia. J Med Genet 45: 228–232
Uliana V, Giordano N, Caselli R, Papa FT, Arani F, Marcocci C, et al (2008) Expanding the phenotype of 22q11 deletion syndrome: the MURCS association. Clin Dysmorphol 17: 13–17
Sundaram UT, McDonald-McGinn DM, Huff D, Emanuel BS, Zackai EH, Driscoll DA, et al (2007) Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome. Am J Med Genet 143A: 2016–2018
Klipstein S, Bhagavath B, Topipat C, Sasur L, Reindollar RH, Gray MR (2003) The N314D polymorphism of the GALT gene is not associated with congenital absence of the uterus and vagina. Mol Hum Reprod 9: 171–174
Timmreck LS, Gray MR, Handelin B, Allito B, Rohlfs E, Davis AJ, et al (2003) Analysis of the cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina. Am J Med Genet 120: 72–76
Oppelt P, Strissel PL, Kellermann A, Seeber S, Humeny A, Beckmann MW, et al (2005) DNA sequence variants of the entire anti-Müllerian hormone (AMH) gene promoter and AMH protein expression in patients with the Mayer-Rokitansky-Küster-Hauser syndrome. Hum Reprod 20: 149–157
van Lingen BL, Reindollar RH, Davis AJ, Gray MR (1998) Further evidence that the WT1 gene does not have a role in the development of the derivates of the müllerian duct. Am J Obstet Gynecol 179: 597–603
Burel A, Mouchel T, Odent S, Tiker F, Knebelmann B, Pellin I, et al (2006) Role of HOXA7 to HOXA13 and PBXI genes in various forms of MRKH syndrome (congenital absence of uterus and vagina). J Negat Results Biomed 5: 4
Timmreck LS, Pan HA, Reindollar RH, Gray MR (2003) WNT7 mutations in patients with müllerian duct abnormalities. J Pediatr Adolesc Gynecol 16: 217–221
Packham EA, Brook J (2003) T-box genes in human disorders. Hum Mol Genet 12: R37–44
Fakih MH, Williamson HO, Seymour EQ, Pai S (1987) Concurrence of the Holt-Oram syndrome and the Rokitansky-Kuster-Hauser syndrome. A case report. J Reprod Med 32: 549–550
Ulrich U, Schrickel J, Dorn C, Richter O, Lewalter T, Luderitz B, et al (2004) Mayer-von Rokitansky-Kuster-Hauser syndrome in association with hitherto undescribed variant of the Holt-Oram syndrome with an aorto-pulmonary window. Hum Reprod 19: 1201–1203
van Bokhoven H, Hamel BC, Bamshad M, Sangiorgi E, Gurrieri F, Duijf PH, et al (2001) p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. Am J Hum Genet 69: 481–492
Vecchietti G (1979) The neovagina in the Robitansky-Kuster-Hauser syndrome. Rev Med Suisse Romande 99: 593–601
Shaffer LG, Tommerup N (eds) (2005) ISCN an international system for human cytogenetic nomenclature. Karger, Basel
Kearney L, Buckle VJ (2001) The application of fluorescence in situ hybridization to chromosome analysis. In: Rooney DE (ed) Human cytogenetics: constitutional analysis. Oxford University Press, New York, pp 175–209
Hammoud AO, Gibson M, Peterson CM, Kerber RA, Mineau GP, Hatasaka H (2008) Quantification of the familial contribution to müllerian anomalies. Obstet Gynecol 111: 378–384
Greene R, Bloch MJ, Huff DS, Iozzo RV (1986) MURCS association with additional congenital anomalies. Hum Pathol 17: 88–91
McDonough PG (2005) Hot clues to the etiology of Mayer-Rokitansky-Küster-Hauser syndrome. Fertil Steril 84: 545
Basson CT, Cowley GS, Solomon SD Weissman B, Poznanski AK, Traill TA, et al (1994) The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome). NEJM 330: 885–891
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hofstetter, G., Concin, N., Marth, C. et al. Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association). Wien Klin Wochenschr 120, 435–439 (2008). https://doi.org/10.1007/s00508-008-0995-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00508-008-0995-4