Sonic hedgehog and bone morphogenetic protein 4 expressions in the hindgut region of murine embryo with anorectal malformations

Purpose

The aim of this study was to determine the possible role of the retinoid-mediated signaling pathway in the pathogenesis of anorectal malformations (ARM). The authors investigated whether all-trans retinoic acid (ATRA) affects the expression pattern of Sonic hedgehog (Shh) and Bone morphogenetic protein 4 (BMP4), which play important roles in anorectal morphogenesis in vertebrates.

Methods

Pregnant ICR strain mice were fed 100 mg/kg of ATRA on the ninth gestational day (E9). Embryos with or without administration of ATRA were obtained from the uteri between E12 and E16 and were fixed immediately in a 4% paraformaldehyde solution. Frozen sections were evaluated for concentric layers around the endodermal epithelium by H&E and immunohistochemistry using antibodies created specifically to act against Shh and BMP4.

Results

More than 95% of the embryos administered ATRA had ARM; rectoprostatic urethral fistula, rectocloacal fistula, and short tail were the most frequent anomalies in the mouse embryos. On E14, normal mouse embryos had normal rectum and anus in which the epithelium of the anorectum was positive for Shh, and the mesenchyme was positive for BMP4. In the ARM embryos, however, the epithelium of the anorectum was negative for Shh, and the mesenchyme was also negative for BMP4.

Conclusions

In normal hindgut development, Shh from the epithelium induces BMP4 expression in the mesenchyme, which differentiates into the lamina propria and the submucosa. In ARM embryos, expressions of Shh and BMP4 could not be found in those regions of the hindgut. Therefore, these findings indicate that Shh and BMP4, which appear to play a crucial role in organogenesis of the hindgut, were disturbed in the cell signaling pathway between the epithelium and the mesenchyme layers.     

Is surgery necessary for asymptomatic tethered cord in anorectal malformation patients?

Background

Evidence supporting routine surgery for asymptomatic tethered cord in patients with anorectal malformation (ARM) is, at best, speculative. The authors therefore examined whether untethering is indicated for asymptomatic tethered cord in patients with ARM.

Methods

A retrospective analysis of all patients with ARM (n = 223) between 1992 and 2002 was conducted. During the same period, 435 patients had surgery for tethered cord.

Results

Tethered cord was detected radiologically in 22 (9.8%); 8 patients with a low conus, and 14 with a low conus with and thickened filum. Seven of 22 patients underwent untethering; 3 prophylatic (14%) and 4 for neuro/motor function deficits (18%). All 4 symptomatic patients had significant clinical improvement in their neuro/motor functions after surgery. However, bowel and urinary functions remained unchanged in all 7 patients with a mean follow-up of 6.4 years (range, 4 to 8 years). Fifteen patients with radiologically diagnosed tethered cord remain asymptomatic with a mean follow-up of 2.7 years (range, 8 months to 10 years).

Conclusions

Neuro/motor functions clearly improved with surgery in symptomatic patients. However, bowel and urinary functions remained unchanged after surgery. Only 4 ARM patients with tethered cord required surgery, whereas prophylactic surgery appears to have minimal benefit. Expectant conservative approach in the management of asymptomatic tethered cord patient appears to be safe.     

Impact of spinal cord malformation on bladder function in children with anorectal malformations

Purpose

Risk factors for the presence of neurogenic bladder dysfunction (NBD) in children born with high anorectal malformations (ARMs), were investigated, to identify the need for urodynamics in these patients.

Material and Methods

The study included 37 patients with high ARMs (21 boys and 16 girls). Bladder function was evaluated with urodynamics both before and after anorectoplasty (posterior sagittal anorectoplasty [PSARP]). All patients were investigated with spinal radiograph. Spinal ultrasound was performed in the neonatal period, and magnetic resonance imaging was added in case of abnormal ultrasound or urodynamics and in case of cloacal malformation.

Results

In ARM patients with rectourethral and vestibular fistulas and cloacas, NBD was identified in 9 children (25%). The bladder dysfunction was innate in all cases except in one girl with cloaca, indicating that the risk of iatrogenic denervation seems minimal using the PSARP technique. All children with innate NBD had a spinal cord malformation either as spinal cord regression or tethering with or without a lipoma. Concerning vertebral status, almost all children with NBD had partial sacral agenesis. Abnormal perineal appearance was highly correlated to NBD in boys, especially in those with a spinal cord regression malformation. Innate NBD was not found in any child with normal spinal cord.

Conclusion

From these results, we suggest that spinal ultrasound and perineal inspection are used as screening procedures for NBD in children with ARM. Urodynamic investigation is recommended only when spinal cord anomalies or other signs indicative of NBD are present. In case of spinal cord malformation, repeated urodynamics during follow-up is mandatory because of the risk for developing tethered cord syndrome.     

Spinal dysraphism with anorectal malformation: lumbosacral magnetic resonance imaging evaluation of 120 patients

Purpose

We evaluated the prevalence of spinal dysraphism (SD) in patients with anorectal malformation (ARM) by magnetic resonance imaging (MRI).

Methods

From January 2002 to March 2009, 120 patients with ARM who underwent anorectal reconstruction were evaluated for SD with sacral plain film, spinal ultrasonography (US), and lumbosacral MRI. We adopted Krickenbeck international classification of ARM.

Results

Spinal dysraphism was present in 41 (34.2%) of 120 patients with ARM, 3 (13.0%) of 23 patients with perineal fistula, 7 (29.2%) of 24 patients with vestibular fistula, 4 (36.4%) of 11 patients with rectovesical fistula, 18 (40.9%) of 44 patients with rectourethral fistula, and 9 (60.0%) of 15 patients with cloacal anomaly (P = .04). Among 41 patients having SD detected by MR, 26 patients (26/41; 63.4%) underwent detethering surgery for tethered spinal cord. The mean sacral ratio (SR) in patients who underwent detethering surgery (0.54 ± 0.19) was significantly lower than in patients who did not undergo detethering surgery (0.69 ± 0.13; P < .001). The optimal cutoff for the SR value predicting SD requiring detethering surgery was 0.605, with sensitivity of 65.4% and specificity of 77.7%.

Conclusions

Spinal dysraphism is common in patients with ARM, and its prevalence is higher in patients with complex ARM. Spinal anomalies can occur even with benign types of ARM and, therefore, that all patients should be screened. Magnetic resonance imaging is useful in detecting occult SD that may be missed by conventional radiologic evaluation, physical examination, and spinal US. We further recommend a lumbosacral MRI examination in those whose SR is lower than 0.6.     

Magnetic resonance angiographic localization of the artery of Adamkiewicz for spinal cord blood supply

Background

The purpose of this study was to determine whether the artery of Adamkiewicz (ARM) can be detected by magnetic resonance angiography and to determine the usefulness of preoperative magnetic resonance angiography evaluation of the ARM.

Methods

Between April 2000 and December 2003, 120 patients underwent magnetic resonance angiography for detection of the ARM. The morphology of the anterior spinal artery at the ARM junction, as revealed by magnetic resonance angiography, in 99 patients in whom ARM was preoperatively detected was classified into the following three types: noncontinuation of the anterior spinal artery above the ARM junction (type A), continuation of the anterior spinal artery above and below the ARM junction (type B), and noncontinuation of the anterior spinal artery below the ARM junction (type C).

Results

The ARMs were detected in 99 (83%) of 120 patients, and from a total of 110 ARMs 105 (95%) originated from intercostal arteries branching from the left side and 94 (86%) originated between Th9 and Th11. Two ARMs were found in 11 (11%) of 99 patients in whom ARMs were detected. In 107 patients, who underwent magnetic resonance angiography to reveal the morphology of the anterior spinal artery at the ARM junction, the patterns of the anterior spinal artery were type A in 59 patients (55%), type B in 21 patients (20%), type C in 3 patients (3%) and not classified in 24 patients (22%). No spinal cord injury occurred in patients in whom the ARM had been preoperatively detected.

Conclusions

Preoperative detection of the ARM is possible by magnetic resonance angiography and is very useful for reducing the incidence of ischemic injury of the spinal cord.     

Normal and abnormal embryonic development of the anorectum in rats

Background

The embryologic and pathologic aspect of anorectal malformation (ARM) remains poorly understood. There is no universally accepted theory to explain anorectal embryology and the abnormal development that produces ARM. The aim of this study was to observe the developmental processes of anorectum in rats and to explore the abnormal embryonic development that leads to ARM.

Methods

Rat embryos with ARM were obtained by treating pregnant rats with administration of ethylenethiourea (ETU). Normal rat embryos and embryos with ARM from gestational days 12.5 to 20 were sectioned serially and sagittally and stained with H & E. The relevant structure including cloaca and urorectal septum (URS) were examined in a temporospatial sequence.

Results

Characteristics of anorectum development in ARM rat embryos treated by ETU were as follows: (1) URS never fused with cloaca membrane. (2) Dorsal cloacal membrane was maldeveloped. (3) Cloacal configuration was abnormal. (4) Tail groove never appeared. All type of ARM was the rectourethal fistula and common cloaca in ETU-treated rat embryos and was discernible on gestation day 16.

Conclusions

Absence of the tail groove and maldevelopment of the dorsal cloacal membrane, cloacal configuration, and urorectal septum are likely to be responsible for the formation of ARM. Failure of fusion of the URS with cloacal membrane is the immediate reason for rectourethral fistula or common cloaca in ETU-treated rats.     

Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations

Background/Purpose

Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (myogenic regulatory factors [MRFs]) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARMs), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM.

Methods

Anorectal malformation embryos were obtained from the 10.5th embryonal day (E10.5) to the 7.0th postnatal day (D7.0) in a natural mutant strain (Sd/+, RSV/Le). Serial frozen sections were prepared for immunohistochemistry using specific antibodies to M-cadherin, myoD, Myogenin, myosin heavy chain, and alfa-actin molecule.

Results

In normal mice, embryonal caudal somites differentiated into myogenic stem cells and migrated to the pelvic floor between E11.0 and E14.0. In the ARM mice, however, caudal somites were irregularly arranged and MRF expressions in myogenic cells were markedly decreased in the dorsocaudal region at E11.5 to E13.0, leading to hypoplastic pelvic floor muscles.

Conclusions

The maldevelopment of pelvic floor muscles in ARM is derived from a deficient supply of myogenic stem cells, with impaired MRF expression. These results suggest that myogenic stem cells, available from bone marrow contents, may be used for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.     

Establishment of a rescue program for anorectal malformations induced by retinoic acid in mice

Aims of Study

Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice.

Methods

Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining.

Results

In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C.

Conclusion

The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future.     

Preliminary report on the International Conference for the Development of Standards for the Treatment of Anorectal Malformations

Background

Anorectal malformations (ARM) are common congenital anomalies seen throughout the world. Comparison of outcome data has been hindered because of confusion related to classification and asssessment systems.

Methods

The goals of the Krinkenbeck Conference on ARM was to develop standards for an International Classification of ARM based on a modification of fistula type and adding rare and regional variants, and design a system for comparable follow up studies.

Results

Lesions were classified into major clinical groups based on the fistula location (perineal, recto-urethral, recto-vesical, vestibular), cloacal lesions, those with no fistula and anal stenosis. Rare and regional variants included pouch colon, rectal atresia or stenosis, rectovaginal fistula, H-fistula and others. Groups would be analyzed according to the type of procedure performed stratified for confounding associated conditions such as sacral anomalies and tethered cord. A standard method for postoperative assessment of continence was determined.

Conclusions

A new International diagnostic classification system, operative groupings and a method of postoperative assessment of continence was developed by consensus of a large contingent of participants experienced in the management of patients with ARM. These methods should allow for a common standardization of diagnosis and comparing postoperative results.     

Development of the pelvic floor muscles of murine embryos with anorectal malformations

Background/Purpose: Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory molecules play key roles during embryogenesis. To determine possible myogenic abnormalities in anorectal malformations (ARM), the authors investigated the pelvic muscle development in murine embryos affected with ARM. Methods: ARM embryos were induced by all-trans retinoic acid (ATRA) on the ninth gestational day (E9.0). Embryonal specimens were obtained from the uteri between E10.5 and E16.0, and the frozen sections were prepared for immunohistochemistry using antibodies specific for MyoD, myogenin, and PGP9.5 molecules. Results: In ARM embryos, the neural tube was irregularly branched and formed an anomalous mass in the sacral region. Embryonal caudal somites differentiated into myogenic cells to form proper myotubes in the pelvis corresponding to the developmental stages between E12.5 and E15.0 both in affected embryos and the controls. Conclusions: In ARM embryos, an impaired anatomic framework of the pelvis was caused by neural maldevelopment, whereas muscle development proceeded physiologically. These results support the hypothesis that pelvic floor muscles may function in ARM children, in whom neural abnormalities such as meningomyelocele or tethered spinal cord have been ruled out, if the surgical correction is appropriately completed.     

Adriamycin induces notochord hypertrophy with conservation of sonic hedgehog expression in abnormal ectopic notochord in the adriamycin rat model

Background/purpose

The Adriamycin rat model (ARM) is a well-established model of the Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb (VACTERL) association. The notochord, which expresses Sonic Hedgehog (Shh), has been found to be grossly malformed with ventral ectopic branches in the foregut region of embryos in the ARM. The authors designed this study to test the hypothesis that Shh-expressing ectopic notochord could contribute to an increased volume of notochord relative to total embryo volume, resulting in an increased concentration of Shh in the notochord of affected embryos.

Methods

Adriamycin was administered intraperitoneally to rats on days 7 (E7), E8, and E9 of gestation and saline to control animals. Embryos recovered at E12 and E14 were examined immunohistochemically for Shh expression. Quantitative morphology using the Cavalieri technique was performed to determine embryo and notochord volume.

Results

Embryos in both Adriamycin and control groups at E12 and E14 showed comparable levels of Shh expression in notochord at all locations. The percentage of notochord per embryo was significantly increased in Adriamycin embryos at E12 and E14 compared with equivalent controls.

Conclusions

These data suggest that Adriamycin induces notochord hypertrophy. With all regions of the notochord secreting Shh, this could result in a higher concentration gradient of Shh in close abnormal proximity to the foregut, possibly contributing to the malformations found in the VACTERL association.     

Notable sequential alterations in notochord volume during development in the Adriamycin rat model

Background/Purpose

The Adriamycin rat model (ARM) is a well-established model of the vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb association. An important finding in the ARM is that Adriamycin induces abnormal notochord morphology in the region of the foregut. Having recently demonstrated notochord hypertrophy in ARM embryos, the authors designed this study to assess notochord volume sequentially from gestational days 10 to 14 (E10-E14) to test the hypothesis that notochord hypertrophy occurs maximally soon after Adriamycin administration.

Methods

Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats on E7, E8, and E9. Control animals were given saline. Embryos were recovered at E10, E11, E12, E13, and E14 and embedded in paraffin. Quantitative morphology using the Cavalieri technique was performed on hematoxylin and eosin-stained transverse serial sections to determine total embryo and total notochord volume.

Results

The percentage volume of notochord per embryo was significantly increased (P < .05) in Adriamycin-treated embryos at all gestational time frames from E10 to E14 when compared with equivalent controls. This increased volume of notochord was found to be maximal at E11.

Conclusions

These data support the authors' previous finding that Adriamycin induces notochord hypertrophy and suggest that notochord volume is increased relative to embryo volume soon after Adriamycin administration and is maximal on E11. The abnormal increase in notochord volume during the critical phase of development may interfere with organogenesis, resulting in the vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb association.     

Embryonic development of the striated muscle complex in rats with anorectal malformations

Purpose

Many patients with anorectal malformations (ARMs) continue to have postoperative anal dysfunction. The striated muscle complex (SMC) is one of the most important factors that influence defecation function. To explore the development of SMC in ARMs, the authors investigated the pelvic muscle development in rat embryos affected with ARMs.

Methods

Anorectal malformation embryos were induced by ethylenethiourea on the 10th gestational day (E10). Normal rat embryos and embryos with ARMs from E13 to E21 were serial-sectioned in the sagittal, transverse, and coronal planes, stained with H&;E and immunohistochemistry staining using specific antibodies to myogenin. Temporal and spatial sequence was carried out on SMC.

Results

On E16, in normal group, SMC appeared fibroid structure in normal rats; SMC arose from bulbocavernosus muscle and ran backward, parallel to the perineal skin, and loosely surrounded the anal canal and urethra. Although in ARM rats the rectum was absent, the location and appearance of SMC were similar to the normal group. On E18, in normal group, SMC musculature became much thicker than on E16 and SMC gave off 2 branches outside anterior to the rectum. Striated muscle complex surrounded the rectum more tightly. However, in ARM rats, obvious changes of SMC could be noted. In detail, SMC in ARMs were characterized by abnormal location, appearance, and path. Striated muscle complex shifted obviously cephalad, ventrally, and medianward and converged inferior to the rectal terminus and posterior to the urethra. The distance between SMC musculature and the perineal skin increased. This structure surrounded the fiberlike tissue posterior to the urethra. Under high-power view, there was connective tissue among intermuscular bundles, and the structure was disordered. During the following gestational days, SMC in normal and ARM groups continued their own tendency, respectively.

Conclusions

This study illustrated the development of the SMC in normal and ARM rats. On E16, the location and appearance of SMC in ARM rats were similar to the normal rats, and at this time, the ectopic rectal orifice could be noted. From E18 on, the maldevelopment of SMC could be observed in ARM rats. These observations suggested that the morphological changes of SMC take place after the occurrence of abnormal anorectum.     

Reduction of caudal traction force using dural sac opening rather than spinal cord detethering for tethered cord syndrome caused by lipomyelomeningocele: a case report

Background context

A few reports have addressed tethered cord syndrome. Detethering surgery has been performed in these cases because abnormal tension on the spinal cord causes neurologic and urologic symptoms.

Purpose

To discuss the surgical treatment of tethered cord syndrome with the belief that the tension on the cord can be decreased by shifting tethered cord to the dorsal side.

Study design

A patient with tethered cord syndrome was surgically treated by shifting the tethered cord to the dorsal side by harnessing the lumbar lordosis instead of detethering.

Methods

We performed surgery to shift the tethered cord to the dorsal side by harnessing the lumbar lordosis to decrease the tension on the spinal cord.

Results

The tethered cord that was pressed to the ventral side because of a lipoma was shifted dorsally by laminectomy and opening of the dural sac. Pain and numbness were alleviated immediately after surgery.

Conclusions

The method used in the present case, that is, shifting the tethered cord and lipoma to the dorsal side by harnessing the lumbar lordosis instead of detethering, is a viable treatment option for tethered cord syndrome.     

Scanning electron microscopy of fetal murine myelomeningocele reveals growth and development of the spinal cord in early gestation and neural tissue destruction around birth

Background

Previous studies demonstrated that the spinal cord within a fetal myelomeningocele (MMC) lesion suffers progressive destruction during gestation. This study aims at elucidating thispathophysiologic feature on a cellular and ultrastructural level in a model of genetically determinedMMC.

Methods

Curly tail/loop tail mouse fetuses at various gestational stages and neonates were analyzed electron-microscopically to document time-point and nature of neural tissue development and pathologic alterations within the MMC.

Results

At embryonic day (E) 8.5 and E9.5, round cells displaying multiple microvilli covered the entire region of interest, and some specimens showed initial stages of neurulation. At E10.5, neurulation was terminated in normal animals, whereas the neural placode remained unfolded in MMC fetuses and became distinguishable from adjacent epidermal layers. At E15.5, an apparently normal differentiation was found. Until this time-point, there was no tissue damage or inflammation. Thereafter, increasingly severe tissue alterations were identified with ongoing gestation leading to almost complete loss of neural tissue at birth.

Conclusion

We show here in fetal mice with MMC that, apart from absent neurulation, growth and development of the otherwise perfectly intact exposed spinal cord appear normal in early gestation, whereas later, the unprotected neural tissue is progressively destroyed.     

A 39-month follow-up study to evaluate the safety and efficacy in kidney transplant recipients treated with modified-release tacrolimus (FK506E)-based immunosuppression regimen

Background

We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E.

Methods

Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation.

Results

In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment.

Conclusion

This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective.     

Increased heritability of certain types of anorectal malformations

Purpose

Various lines of evidence point to genetic causes for the diverse spectrum of anorectal malformations (ARMs); we therefore studied patterns of heritability in a large case series.

Methods

We searched our ARM database for all patients having family members with congenital anomalies. This group was analyzed to determine the type of ARM and the specific anomalies in affected family members.

Results

Thirty-nine of 1606 patients (2.4%) had a family member with a congenital anomaly. The associated non-ARM anomalies included sacral masses and gynecologic, hematologic, esophageal, duodenal, renal, and spinal anomalies. Of these, 24 patients (1.4%) had 1 or more family members with an ARM. Among females with a positive family history, 73% of patients had either a vestibular or perineal fistula, compared with only 36% in patients without a family history (P = .0004). Among males, 35% had perineal fistulas compared with only 10% of those without affected family members (P = .0051).

Conclusions

A positive family history in 1.4% is supportive of a strong genetic component to ARM. The risk of having an affected family member is significantly increased in the presence of a vestibular or perineal fistula. These new data allow for more informed counseling of families with an ARM and support the need for further genetic studies.     

Cervical cord compression by hereditary multiple exostosis: case report and review of literature

Background

Hereditary multiple exostosis (HME) is an hereditary disease, characterized by the presence of multiple osteochondromas; 7% of patients with HME have a spinal disease. Through this observation, the authors discuss the diagnostic and therapeutic aspects of this rare lesion.

Case report

A 45-year-old woman, operated 10 years ago for an exostosis of the right fibula and left femur. She has since few years paresthesia of all four limbs with distal predominance, walking fatigability kind of spinal claudication. The MRI shows a voluminous osteoma at the second cervical vertebra compressing the spinal cord. The patient was operated with macroscopically complete resection of the exostosis and C2 laminectomy.

Conclusion

The cervical exostosis associated with HME is a rare disease. The clinical symptomatology is dominated by spinal cord compression and surgical treatment allows excellent clinical results.