A combination of the congenital abnormalities, Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia, is defined as the MURCS association. Various genetic defects have been described in the MURCS association so far, yet the unambiguous molecular basis of these disorders has not been established. We report the case of an 18-year-old woman who presented with primary amenorrhea, right kidney, Arnold-Chiari malformation, and Klippel-Feil syndrome. In addition, the patient showed the following unusual features: right ovarian and Skenes gland agenesis, cubitus valgus with hyperextension and decreased range of motion at elbows, and facial changes. Moreover, the performed DNA analysis showed interstitial duplication in chromosome 5 (5q35.1). In the duplicated region, there are genes whose function is not well known. It is thought that they have an influence on the early stages of development and their joining in the later period can lead to neoplastic disorders, especially leukemias. 1. Background MURCS association is the combined occurrence of the following disorders: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. Cervicothoracic somite dysplasia is described in Klippel-Feil syndrome (KFS). Changes in the relations in the base of the neck and head can lead to the development of Arnold-Chiari malformation (ACM). ACM is a congenital malformation of the central nervous system, traditionally defined as downward herniation of the cerebellar tonsils through the foramen magnum [1]. In our case, in addition to the typical features, the following abnormalities are unusual for MURCS association: right ovarian and Skenes gland agenesis, cubitus valgus with hyperextension and decreased range of motion at elbows, and changes in facial appearance [2–5]. MURCS girls are karyotypically female (46, XX). Various genetic defects have been described in the MURCS association so far, yet the unambiguous molecular basis of these disorders has not been established [6, 7]. The relationship of 5q35.1 duplication with characteristic features for the MURCS association is interesting. In the accessible literature, we have not found the connection of this chromosomal duplication of 5q35.1 with MURCS association. 2. Case History The 18-year-old patient was admitted to the Gynecological Endocrinology Department because of primary amenorrhea (Figure 1). Figure 1: The phenotype of the patient. Her height was 1.56？m, weight 66？kg, BMI 27？kg/m2, and occipitofrontal head circumference 59？cm (>97th percentile). She was born at term with
References
[1]
A. A. Khan, S. N. Bhatti, G. Khan et al., “Clinical and radiological findings in Arnold Chiari malformation,” Journal of Ayub Medical College, Abbottabad, vol. 22, no. 2, pp. 75–78, 2010.
[2]
J. P. Mendez, A. Ulloa-Aguirre, F. J. Sánchez, O. Mutchinick, and G. Pérez-Palacios, “Endocrine evaluation in a patient with MURCS association and ovarian agenesis,” European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 22, no. 3, pp. 161–169, 1986.
[3]
J. J. Gorgojo, F. Almodóvar, E. López, and S. Donnay, “Gonadal agenesis 46,XX associated with the atypical form of Rokitansky syndrome,” Fertility and Sterility, vol. 77, no. 1, pp. 185–187, 2002.
[4]
A. Kumar, S. Mishra, and P. N. Dogra, “Management of an unusual case of atypical Mayer-Rokitansky-Kuster-Hauser syndrome, with unilateral gonadal agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction,” International Urogynecology Journal and Pelvic Floor Dysfunction, vol. 18, no. 7, pp. 823–825, 2007.
[5]
S. T. Pittock, D. Babovic-Vuksanovic, and A. Lteif, “Mayer-Rokitansky-Küster-Hauser anomaly and its associated malformations,” American Journal of Medical Genetics, vol. 135, no. 3, pp. 314–316, 2005.
[6]
P. Oppelt, S. P. Renner, A. Kellermann et al., “Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging,” Human Reproduction, vol. 21, no. 3, pp. 792–797, 2006.
[7]
A. G. M. López, J. P. Fryns, and K. Devriendt, “MURCS association with duplicated thumb,” Clinical Genetics, vol. 61, no. 4, pp. 308–309, 2002.
[8]
A. G. W. Hunter, B. Dupont, M. McLaughlin et al., “The Hunter-McAlpine syndrome results from duplication 5q35-qter,” Clinical Genetics, vol. 67, no. 1, pp. 53–60, 2005.
[9]
C. Vergnes, M. P. Cordier, R. Dubois, R. Bouvier, and P. Cochat, “MURCS association: a challenging diagnosis,” Archives de Pediatrie, vol. 12, no. 1, pp. 49–51, 2005.
[10]
M. Komura, Y. Kanamori, M. Sugiyama et al., “A female infant who had both complete VACTERL association and MURCS association: report of a case,” Surgery Today, vol. 37, no. 10, pp. 878–880, 2007.
[11]
A. Al Kaissi, F. Ben Chehida, M. Ben Ghachem, F. Grill, and K. Klaushofer, “Occipitoatlantoaxial junction malformation and early onset senile ankylosing vertebral hyperostosis in a girl with MURCS association,” American Journal of Medical Genetics A, vol. 149A, no. 3, pp. 470–474, 2009.
[12]
G. Hofstetter, N. Concin, C. Marth, T. Rinne, M. Erdel, and A. Janecke, “Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association),” Wiener Klinische Wochenschrift, vol. 120, no. 13-14, pp. 435–439, 2008.
[13]
D. Guerrier, T. Mouchel, L. Pasquier, and I. Pellerin, “The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina)—phenotypic manifestations and genetic approaches,” Journal of Negative Results in BioMedicine, vol. 5, article 1, 2006.
[14]
S. Klipstein, B. Bhagavath, C. Topipat, L. Sasur, R. H. Reindollar, and M. R. Gray, “The N314D polymorphism of the GALT gene is not associated with congenital absence of the uterus and vagina,” Molecular Human Reproduction, vol. 9, no. 3, pp. 171–174, 2003.
[15]
L. S. Timmreck, M. R. Gray, B. Handelin et al., “Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina,” American Journal of Medical Genetics, vol. 120, no. 1, pp. 72–76, 2003.
[16]
S. Ledig, C. Schippert, R. Strick, M. W. Beckmann, P. G. Oppelt, and P. Wieacker, “Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Küster-Hauser syndrome,” Fertility and Sterility, vol. 95, no. 5, pp. 1589–1594, 2011.
[17]
D. A. Koolen, J. Herbergs, J. A. Veltman et al., “Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1,” Journal of Human Genetics, vol. 51, no. 8, pp. 721–726, 2006.
[18]
T. Y. Tan, C. Whitelaw, and R. Savarirayan, “A patient with Mullerian abnormalities, renal dysplasia, cervical spine fusion, cataracts and intellectual disability: MURCS-plus?” Clinical Dysmorphology, vol. 16, no. 4, pp. 271–273, 2007.
