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Burina et al., 1:10http://dx.doi.org/10.4172/scientificreports.468

Case Report Open Access

Open Access Scientific ReportsScientific Reports

Open Access

Volume 1 • Issue 10 • 2012

Keywords: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome; Neurology; Spinal blood vessel malformations

IntroductionThe Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is

characterized by complete or partial congenital aplasia of the uterus and vagina. It may be isolated (type I MRKH syndrome) or associated with renal, cardiac, and skeletal anomalies, short stature, and auditory defects (type II MRKH syndrome). The incidence of MRKH syndrome is approximately 1/4500 women. Women with MRKH syndrome typically present with primary amenorrhea but otherwise have normal development of secondary sexual characteristics and external genitalia [1]. While the etiology of MRKH syndrome remains unclear [2,3], there is evidence for both a developmental and genetic basis for this syndrome. Defects in the Wnt signaling pathway have been implicated specifically loss-of-function mutations in the WNT4 gene [4-6]. Additionally, malformations in organ systems that are closely related during embryogenesis are indicative of a potential developmental component [1].

Case ReportA thirty year old female with a history of slowly progressing lower

extremity weakness leading to flaccid paraplegia was hospitalized in the Department of Neurology at the University Clinical Center, Tuzla. These symptoms worsened over a period of two years. Two months prior to being admitted, weakness in the distal muscle groups in her right leg worsened to the point where she required a mobility aid in order to walk. Her left leg continued to worsen as well. She experienced numbness in her perianal region, urinary incontinence, and loss of bowel control. She did not report any associated pain. Few days before admittance to neurology she visited gynaecologist. The reason was her inability to become pregnant. A gynaecologist noted primary amenorrhea and genital abnormalities. Furthermore, due to her deficiencies in gross motor function and associated perianal numbness she was referred to neurology.

*Corresponding author: Adnan Burina, Department of Neurology, University Clinical Center Tuzla, 75000 Tuzla, Bosnia and Herzegovina, Tel: 011-387-61-132940; E-mail: burina@bih.net.ba

Received August 10, 2012; Published September 22, 2012

Citation: Burina A, Sinanović O, Mujagić S, Burina M, Arnautalić L, et al. (2012) Mayer-Rokitansky-Kuster-Hauser Syndrome with Neurological Features. 1:468. doi:10.4172/scientificreports.468

Copyright: © 2012 Burina A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

AbstractThe Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by complete or partial congenital

aplasia of the uterus and vagina. It may be isolated (type I MRKH syndrome) or associated with renal, cardiac, and skeletal anomalies, short stature, and auditory defects (type II MRKH syndrome). In this case study, we report a thirty year old woman with a history of slowly progressing weakness in her lower extremities that ultimately resulted in flaccid paraplegia that was associated with numbness in her perianal region and urinary incontinence. During hospitalization primary amenorrhea was confirmed and genital malformations were detected via a gynecological exam and Magnetic Resonance Imaging (MRI) of the pelvis. Furthermore, an MRI of the entire spine showed structural abnormalities in the thoracic and lumbar regions of the spine as well as extradural, intradural-extramedullary and intramedullary blood vessel abnormalities. A Computerized Tomographic (CT) urography was normal. An electromyoneurography pointed out significant damage to the lumbosacral plexus implicating cauda equina syndrome. According to our best knowledge and extensively searching the literature, this is the first case of MRKH syndrome with neurological issue and spinal blood vessels malformations. Our findings suggest that is important for neurologists to consider the potential implication of MRKH syndrome when presented with a patient suffering from lower motor neuron disorders and sensory disturbances.

Mayer-Rokitansky-Kuster-Hauser Syndrome with Neurological FeaturesAdnan Burina1*, Osman Sinanović1, Svjetlana Mujagić2, Mensura Burina2, Lejla Arnautalić2, Zlatan Fatusić3, Biljana Kojić1 and Mirjana Vidović1

1Department of Neurology, University Clinical Center Tuzla, 75000 Tuzla, Bosnia and Herzegovina2Department of Radiology, University Clinical Center Tuzla, 75000 Tuzla, Bosnia and Herzegovina3University Clinical Center Tuzla, Department of Gynaecology and Obstetrics, 75000 Tuzla, Bosnia and Herzegovina

After admittance to neurology, her cranial nerve function was found to be normal. During spinal nerve function assessments she was able to elevate her hands with normal strength in all muscle groups. She was unable to stand or walk and had only a minimal ability to move her toes. The Lasegue test and Patrick’s test were negative. Tendon reflexes of her upper extremities were normal but were bilaterally absent in her lower extremities. The patient exhibited a normal plantar reflex. There was evidence for bilateral hypotrophy of the distal muscle groups in both legs. Furthermore, perianal numbness and lack of bladder and bowel control were present. A notable feature included hirsutism limited to her facial region.

Blood panels including a Complete Blood Count (CBC), a Basic Metabolic Panel (BMP), a partial liver panel (total bilirubin and transaminase), as well as magnesium and iron levels were measured and found to be normal, as was the patient’s lipid profile and glycemic index.

Testosterone levels of 4.2 nmol/L were above the normal range of 0.3-3.4 nmol/L. The patient’s karyotype was 46, XX. Audiology testing was normal as was an ultrasonography of her abdominal organs. An ultrasonography of the patient’s reproductive organs verified aplasia of the uterus what was visualized by Magnetic Resonance Imaging (MRI) of the pelvis as well (Figures 1 and 2).

Structural abnormalities of the thoracic and lumbar regions of

Citation: Burina A, Sinanović O, Mujagić S, Burina M, Arnautalić L, et al. (2012) Mayer-Rokitansky-Kuster-Hauser Syndrome with Neurological Features. 1:468. doi:10.4172/scientificreports.468

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the spine as well as dilated, serpiginous, tortuous blood vessels at various regions of the spine were seen as a result of an MRI of the spine (Figures 3-7). A cardiac ultrasonography exam was normal. An Electromyography (EMG) showed severe lack of motoneuron function in the quadriceps, tibialis and extensor digitorum brevis muscles in both legs, with almost complete neurogenic atrophy of both feet. Nerve Conduction Velocities (NCV) was normal in the upper extremities, but it was found that the left extensor digitorium brevis was innervated by the tibial nerve what is uncommon nerve's link. Electromyoneurography (EMNG) exam showed significant damage to the lumbosacral plexus indicating cauda-equina syndrome. Computerized Tomographic (CT) urography was normal. The clinical evaluation combined with the results of diagnostic examinations led to the conclusion that the patient’s neurological abnormalities are associated to MRKH syndrome.

Gynecologists, orthopedists and neurosurgeons were consulted. The patient was not motivated neither to pursue genital reconstructive surgery nor any orthopedic or neurosurgery. Therapeutically, physical rehabilitation was recommended and the patient was sent to the Clinic of Physical Medicine and Rehabilitation at the University Clinical Center Tuzla for treatment. After one year the patient was able to stand alone, but required a walking aid. Her bladder and bowel control showed slight improvement. It is likely that the low socioeconomic

status of this patient may have significantly contributed to her delayed diagnosis and initial referral to neurology.

DiscussionThe MRKH syndrome (type I) is characterized by congenital aplasia

of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics [1]. The usually karyotype of these women is normal (46, XX) [7]. Other malformations can be associated with this syndrome including renal malformations that include unilateral renal agenesis (in 23-28% of cases), ectopia of one or both kidneys (in 17% of cases), renal hypoplasia (in 4% of cases),

Figure 1: Hypoplastic uterus-The axial T2-weighted MRI shows a hypoplastic uterus (arrow).

Figure 2: Incomplete aplasia of uterus. The sagittal T1-weighted fat saturation contrast enhanced MRI shows the incomplete aplasia of the uterus.

Figure 3: Thoracolumbar scoliosis-The coronal T2-weighted MRI shows left thoracolumbar scoliosis of T10 and L4 butterfly vertebrae.

Figure 4: Vertebral wedging-The sagittal T2-weighted MRI shows anterior wedging of T10 vertebra (arrow) suggestive of butterfly vertebra.

Citation: Burina A, Sinanović O, Mujagić S, Burina M, Arnautalić L, et al. (2012) Mayer-Rokitansky-Kuster-Hauser Syndrome with Neurological Features. 1:468. doi:10.4172/scientificreports.468

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horseshoe kidney and hydronephrosis [8]. Furthermore, about 40% of cases have upper urinary tract malformations [9]. While our patient did show the characteristic signs of congenital aplasia of the uterus (Figures 1 and 2) and the upper part of the vagina with normal secondary sexual characteristics and karyotype, she lacked any of the potential renal and urinary malformations. Skeletal anomalies associated with MRKH syndrome mainly involve the spine (in 30 to 40% of cases) [8,9] and include scoliosis, vertebral arch disturbances at C4-C5 [10], and asymmetric, fused or wedged vertebrae (Klippel-Feil association) [9]. Furthermore, hearing defects, cardiac and digital abnormalities can also be present in MRKH syndrome [1]. Our patient presented with thoracolumbar scoliosis at T10 and L4 butterfly vertebrae (Figures 3 and 4) as well as spinal blood vessels malformations (Figures 5-7), which have not been previously reported in the literature. Spinal vascular malformations are rare in the general population (5-10 incidences/year/million people) and constitute only 1% to 2% of all vascular neurologic pathologies [11]. There are three major types of spinal vascular malformations, spinal Arteriovenous Malformation (AVM), spinal Arteriovenous Fistula (AVF) and spinal cavernoma [12], each of which can present with a broad variety of symptoms [13].

Our patient had dilated intra and extramedullary serpiginous vessels with a large nidus at the T11-T12 level and extramedullary tortuous vessels in the posterior subarachnoid space above the T11 level (Figure 5). Furthermore, the T11-T12 level showed an intramedullary nidus corresponding to an aneurisma in the arteriovenous malformation (Figure 6). There was also evidence for spinal cord edema (Figure 5) and the dilation of the draining veins in the cervical spine (Figure 7). These spinal blood vessel malformations were likely the cause of our patient's deficiencies in gross motor function of her lower extremities and associated perianal numbness. This is a novel case where the spinal blood vessel malformations and neurological symptoms documented in our patients are associated with MRKH syndrome and very likely could be a new variation of this syndrome.

ConclusionPatients with Mayer-Rokitansky-Kuster-Hauser's syndrome are

extremely rare cases in neurology. According to our best knowledge and extensively searching the literature this is the first case of Mayer-Rokitansky-Kuster-Hauser's syndrome with neurological issue and spinal blood vessels malformations. The relationship between neurological symptoms and Mayer-Rokitansky-Kuster-Hauser's syndrome need to be better understood and documented in order for neurologists and gynaecologists to be able to better diagnose this disorder. Furthermore, depending on patient socioeconomic status, patients with this syndrome may initially present with neurological disorders as opposed to the traditional symptom of primary amenorrhea. It is especially important for neurologists to therefore, consider the potential implication of MRKH syndrome when presented with a patient suffering from lower motor neuron disorders and sensory disturbances.

References

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2. Guerrier D, Mouchel T, Pasquier L, Pellerin I (2006) The Mayer-Rokitansky-Kuster-Hauser syndrome (congenital absence of uterus and vagina)-phenotypic manifestations and genetic approaches. J Negat Results Biomed 5: 1.

3. Kobayashi A, Behringer RR (2003) Developmental genetics of the female reproductive tract in mammals. Nat Rev Genet 4: 969-980.

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Figure 5: Spinal blood vessel malformations-The sagittal T2-weighted MRI shows dilated intra and extramedullary serpiginous vessels with a large nidus at T11-T12 level (black arrow) and extramedullary tortuous vessels in the posterior subararachnoid space above the T11 level. The image also shows T2-weighted hyperintensity in the spinal cord that corresponds to spinal cord edema (white arrow).

Figure 6: Intramedullary nidus-The axial contrast enhanced T1-weighted MRI at the T11-T12 level shows the intramedullary nidus (arrow) that corresponds to an aneurisma in the arteriovenous malformation.

Figure 7: Spinal vessel dilation-The sagittal T2-weighted MRI indicates dilated draining veins shown as flow voids in the posterior subarachnoid space of the cervical spine.

Citation: Burina A, Sinanović O, Mujagić S, Burina M, Arnautalić L, et al. (2012) Mayer-Rokitansky-Kuster-Hauser Syndrome with Neurological Features. 1:468. doi:10.4172/scientificreports.468

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6. Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, et al. (2008) Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab 93: 895-900.

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13. Krings T (2010) Vascular Malformations of the Spine and Spinal Cord : Anatomy, Classification, Treatment. Clin Neuroradiol.