FERTILITY AND STERILITY威 VOL. 80, NO. 3, SEPTEMBER 2003 Copyright ©2003 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Monozygotic twins discordant for vaginal agenesis and bilateral tibial longitudinal deficiency Michael P. Steinkampf, M.D., Sejal P. Dharia, M.D., and Ryan D. Dickerson, M.D. Division of Reproductive Endocrinology and Infertility, University of Alabama at Birmingham, Birmingham, Alabama
Objective: To report the first case of monozygotic twins with discordant congenital anomalies. Design: Descriptive case report. Setting: University hospital. Patient(s): A 20-year woman with complete vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) and right renal agenesis presented for creation of a neovagina. She had a monozygous twin confirmed by DNA testing using short tandem repeat (STR) loci; the twin had normal mullerian/mesonephric development but isolated bilateral tibial longitudinal deficiency. Intervention(s): The complete history, physical, and laboratory data of both the patient and her twin. Also, operative laparoscopy with creation of a neovagina in the patient. Main Outcome Measure(s): Diagnosis and appropriate treatment of Mayer-Rokitansky-Kuster-Hauser syndrome and DNA testing with STR loci for monozygosity. Result(s): The surgical resection of the bilateral uterine remnants, creation of a neovagina in the patient, and the demonstration of monozygosity with her twin with bilateral tibial longitudinal deficiency. Conclusion(s): This case report suggests a link between developmental abnormalities of the genital and skeletal system. (Fertil Steril威 2003;80:643–5. ©2003 by American Society for Reproductive Medicine.) Key Words: Mayer-Rokitansky-Kuster-Hauser syndrome, bilateral tibial longitudinal deficiency, limb and urogenital embryology, vaginal atresia
Received September 16, 2002; revised and accepted January 27, 2003. Reprint requests: Michael P. Steinkampf, M.D., Department of Obstetrics and Gynecology, 547 Old Hillman Building, 619 19th Street South, Birmingham, Alabama 35249-7333 (FAX: 205-975-5732; E-mail:
[email protected]). 0015-0282/03/$30.00 doi:10.1016/S0015-0282(03) 00758-1
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndromeis a form of mullerian dysgenesis typically involving congenital absence of the vagina; a 46,XX karyotype; a rudimentary uterus; normal ovarian function; normal secondary sexual characteristics; and a frequent association with renal; skeletal; and other congenital abnormalities. The etiology of this syndrome remains obscure. We report the first case of a woman with MRKH syndrome with a monozygotic twin having a normal vagina but an unusual skeletal birth defect.
CASE REPORT A 20-year-old white woman presented for evaluation and therapy of vaginal agenesis. Development of the breast and pubic hair began at age 12 years. She reported intermittent rightsided pelvic pain since the age of 12 years. She first sought gynecologic care at the age of 15
years for primary amenorrhea. At that time, a pelvic exam revealed an absence of the vagina, with a small dimple at the perineum. Folliclestimulating hormone, LH, and prolactin levels were all normal. An abdominal and pelvic ultrasound revealed complete absence of the vagina and uterus and absence of the right kidney. She was referred to the authors at age 20 years for vaginal reconstruction. On physical examination, the patient had Tanner stage IV breast development and escutcheon. The vagina was absent, and there was a small dimple between the urethra and anus. Rectovaginal examination revealed no uterus. At this time, she revealed that she had an identical twin sister who began menses at age 14 years, with normal development of secondary sexual characteristics and no genitourinary symptoms; however, the sister has isolated bilateral longitudinal tibial deficiency. 643
FIGURE 1 MRKH syndrome in one twin (left) and bilateral tibial longitudinal deficiency in her twin sister with bilateral prostheses (arrows).
method using unlinked short tandem repeat (STR) loci to confirm their monozygosity. Using 7 unlinked STRs, there was a chance of ⬎99.9% that the twins were genetically identical. The patient also underwent a peripheral blood karyotype that was 46,XX and Giemsa banding studies that did not demonstrate any structural abnormalities. The patient decided to undergo a vaginal reconstruction using a split-thickness skin graft with concurrent laparoscopy to evaluate her pelvic pain. Intraoperatively, normal fallopian tubes and ovaries were encountered. Just adjacent to the left ovary was a 4 ⫻ 3 ⫻ 2-cm uterine remnant, which was excised. On the right, a 2 ⫻ 1 ⫻ 1-cm uterine remnant was excised. Pathology revealed no functioning endometrial tissue. After the laparoscopy, an Abbe-Wharton-McIndoe vaginal reconstruction was performed in the usual fashion. The postoperative course was uncomplicated, and at the 4-week postoperative visit, the vagina was 12 cm long, well healed, and admitted a Graves speculum without difficulty. She subsequently married and reports satisfactory sexual intercourse without the need for lubrication.
DISCUSSION
Steinkampf. Monozygotic twins. Fertil Steril 2003.
There was no history of parental consanguinity, no family history for congenital anomalies, and no history of mental retardation. There was no prenatal exposure to teratogens such as radiation, infections, or medications. Her mother reported that the pregnancy for the twins was uncomplicated. The patient’s twin sister had been followed by an orthopedist since infancy for bilateral tibial longitudinal deficiency. She underwent multiple surgeries and eventually had prostheses placed to facilitate walking (Fig. 1). Her physical exam was significant for the presence of bilateral hypertrophied fibulas with absent tibias. The tali were missing bilaterally, and the feet were both missing a single digit. The patient also had short femurs, bilateral coxa vera, and highriding trochanters of both femurs with proximal focal femoral deficiency. Her pelvic exam was normal. Buccal mucosal cells were collected from both twins for a polymerase chain reaction (PCR)-based DNA-typing 644
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Mayer-Rokitansky-Kuster-Hauser syndrome occurs in 1:4 –5,000 women. Associated skeletal anomalies include wedge vertebrate, fused vertebrate, rudimentary vertebral bodies, supernumerary vertebrate, absent digits, syndactyly, or hypoplasia of the thenar eminence (1). There are numerous reports in the literature evaluating various urogenital anomalies with skeletal anomalies of the upper extremity, vertebrate, and the feet and the digits, yet only one referring to hypoplasia of the tibial and peroneal muscles. There is also one report in the literature that examines discordant vaginal agenesis among monozygotic twins, where one twin had a normal vagina and the second twin had vaginal agenesis. No common etiology was found (2). To our knowledge, this is the first report of discordant anomalies in monozygotic twins of MRKH syndrome and bilateral longitudinal tibial deficiency. This case affirms a link between the development of the skeletal system and genitourinary tract. This association may be related to the close proximity of the cervicothoracic somite and the pronephros in the caudal mesoderm. Because both the genitourinary and the skeletal systems develop at the same gestation (10 –11 mm embyro length), a single developmental defect may adversely affect both systems (3). Hox genes, which are homeotic selector genes, are important in the development of the skeletal and reproductive tracts. There appears to be an association of the limb bud and genital bud with Hox 9, 10, 11, and 13. It is possible that a defect in one or many of these related genes could lead to the constellation of anomalies seen in our case report (4). Vol. 80, No. 3, September 2003
References 1. Griffin J, Edwards C, Madden J, Harrod M, Wilson J. Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Ann Intern Med 1976;85:224 –36. 2. Lischke JH, Curtis C, Lamb E. Discordance of vaginal agenesis in monozygotic twins. Obstet Gynecol 1973;41:920 –4.
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3. Evans J, Chudley A. Tibial agenesis, femoral duplication, and caudal midline anomalies. Am J Med Genet 1999;85:13–9. 4. Taylor HS, Heuvel GBV, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod 1997;57:1338 – 45.
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