Leiomyomatosis peritonealis disseminata in association with Currarino syndrome?
© Nappi et al; licensee BioMed Central Ltd. 2006
Received: 27 October 2005
Accepted: 10 May 2006
Published: 10 May 2006
Leiomyomatosis peritonealis disseminata (LPD) is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity. No reports of multiple congenital malformations associated with LPD have been found in the English literature.
A 27 year-old patient referred to our gynaecology unit for pelvic pain, amenorrhoea, stress incontinence, chronic constipation and recurrent intestinal and urinary infections. Multiple congenital malformations had previously been diagnosed. Most of these had required surgical treatment in her early life: anorectal malformation with rectovestibular fistula, ectopic right ureteral orifice, megadolichoureter and hemisacrum.
An ultrasound scan and computed tomography performed in our department showed an irregular, polylobate, complex 20 cm mass originating from the right pelvis that reached the right hypochondrium and the epigastrium. The patient underwent laparotomy. The three largest abdominal-pelvic masses and multiple independent nodules within the peritoneum were progressively removed. The histological diagnosis was of LPD.
The case we report is distinctive in that a rare acquired disease, LPD, coexists with multiple congenital malformations recalling a particular subgroup of caudal regression syndrome: the Currarino syndrome.
Leiomyomatosis peritonealis disseminata (LPD), also known as diffuse peritoneal leiomyomatosis, is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity . These nodules, though histologically benign, cannot be distinguished macroscopically from peritoneal carcinomatosis.
The aetiology is thought to be smooth muscle metaplasia of the subperitoneal mesenchyme . About 100 documented cases were found in the English language literature; LPD patients are mainly females of reproductive age , and only rarely have cases affecting men been reported [4, 5]. The condition is associated with high levels of exogenous and endogenous female gonadal steroids (e.g. pregnancy, prolonged exposure to oral contraceptives and/or combined hormonal replacement therapy, granulomatous cell tumours of the ovary) [4, 6], indicating that oestrogens and progestins play an important role in the pathogenesis of LPD as they do in leiomyomata uteri. Most LPD cases are clinically benign, and in some instances the lesions may partially or completely regress [5, 7]. Alternatively, LPD may progress, recur or (rarely) undergo malignant transformation .
We report a case of a patient affected by LPD in whom multiple congenital malformations recalling Currarino syndrome (CS; OMIM 176450) were previously diagnosed. CS is a rare form of caudal regression syndrome (CRS), consisting in anorectal malformation (ARM), sacral bone deformity and presacral mass . The gene responsible for CS is HLXB9 [10, 11], which encodes a transcription factor and is expressed in the anterior horn regions of the spinal cord in human embryos.
A 27 year-old nulliparous Caucasian female was referred to our Gynaecology Unit with a 7-month history of pelvic pain and amenorrhoea. She also complained of stress incontinence, chronic constipation and recurrent intestinal and urinary infections. Her previous history was characterised by several congenital malformations, most of which had required surgical treatment. Neonatally, she had undergone anoplasty for an anorectal malformation with a rectovestibular fistula. Two months after birth, a laparotomy showed a hydronephrosis caused by obstruction of the ectopic right ureteral orifice, which had also caused megadolichoureter and recurrent urinary sepsis. A cutaneous ureterostomy was performed to improve renal function. However, two months later, she underwent a further laparotomy following an urography showing decreased renal function. Right nephrectomy was performed. The histological diagnosis was chronic pyelonephritis.
Furthermore, she had been diagnosed with right hand thumb torsion of the metacarpal-phalangeal articulation with hypotrophy of the tenar eminence, valgus and hemisacrum (type IV sacral malformation) , and a bladder dysfunction that was treated pharmacologically. A standard karyotype on peripheral blood cells showed a normal female karyotype (46 XX) with no numerical or structural chromosomal abnormalities.
An ultrasound performed in our department showed a complex mass originating from the right pelvis that reached the right hypochondrium and the epigastrium. The transverse extension was more than 20 cm. Fluid was noted in the Douglas pouch. Computerized tomography (CT) of the abdomen and pelvis confirmed a suspicious irregular polylobate complex mass of 24 × 19.5 × 13.5 cm; uterus and adnexa were not identified. Chest X-ray and CT were negative for pleural effusion or lung metastasis.
The final diagnosis, confirmed by two independent pathologists with expertise on smooth-muscle cell tumours, was LPD.
Among the features typical of CS, our patient presented only hemisacrum and anorectal malformation. These findings suggested that the patient might have harboured a pathological mutation in the HLXB9 gene. We therefore performed Polymerase Chain Reaction (PCR) amplification of the three exons, intron-exon boundaries, intron 2, and the entire 5' and 3' untranslated regions (UTR) of the gene. The amplified PCR products were sequenced and analysed using a CEQ2000XL DNA Analysis System (Beckmann Coulter, Fullerton, CA, USA). We identified no variations with respect to the reference sequence (GenBank accession number NM 005515), except for the variant *164^65insC in the 3' UTR. This variation was also present in pooled DNA from 10 healthy individuals, demonstrating that it is a benign polymorphism.
The aetiology of LPD is unknown, but it is thought to originate from metaplasia of submesothelial, multipotent mesenchymal cells. The developing leiomyomatous nodules probably arise from Mueller's epithelium, which is distributed throughout the subperitoneal mesenchyme. In cases of individual predisposition and hormonal stimulation, Muellerian derivatives proliferate along lines of myofibrous differentiation [6, 13].
LPD is most common in women of reproductive age. More than half of all patients are pregnant or taking oral contraceptives at the time of diagnosis .
Quade et al. showed that LPD has molecular-genetic and cytogenetic features suggesting that individual tumourlets are monoclonal, with a pathogenesis similar to leiomyomata uteri. In LPD, the smooth muscle cells are influenced by oestrogens [7, 15], and sex steroid receptors have been identified in nearly all cases . LPD can be associated with other oestrogen-dependent diseases including endometriosis, ovarian clear cell carcinoma, endometrial carcinoma  and ovarian fibrothecoma . Recently, two cases of development of LPD and ovarian Brenner tumour during tamoxifen therapy have been reported [18–22].
Although LPD is most common in premenopausal women, cases have been reported in postmenopausal women using  or not using [13, 24, 25] hormone replacement therapy (HRT). The identification of luteinizing hormone (LH) receptors in LPD nodules from a postmenopausal woman suggests that the typical postmenopausal increase in LH levels might affect the pathogenesis of this condition .
Recently, familial occurrence of LPD has been described, showing an autosomal dominant model with varying degrees of penetrance .
Most patients with LPD present without specific symptoms and many documented cases of LPD have been discovered incidentally during surgery (caesarean section, laparotomy or laparoscopy). Sometimes patients may present with mostly non-specific symptoms, such as irregular, heavy uterine bleeding and pain or a mass in the lower abdomen , discomfort, urinary frequency (due to the effect of the mass on the bladder), gastrointestinal bleeding and peritonitis (following erosion of LPD implants in the bowel wall) [7, 13, 18, 28]. Sometimes patients experience symptoms directly related to LPD: urosepsis secondary to obstruction of the ureters, and an acute abdomen due to ovarian torsion .
Sonographic and CT findings reported in the literature include non-specific, solid, and complex soft tissue masses that are often large and mimic a leiomyomatous uterus. In some cases, the masses grow in a fashion similar to that of normal uterine parenchyma, whereas others demonstrate heterogeneous enhancement. Diagnosis may be confused with peritoneal carcinomatosis if the masses are present diffusely throughout the abdomen and pelvis. Peritoneal carcinomatosis, however, is often associated with tumour cake, ascites and liver metastases, which have not been reported with LPD .
Magnetic Resonance (MR) findings include masses similar in signal intensity to skeletal muscle or uterine parenchyma, and when sarcomatous transformation occurs these are not significantly different from the features of benign implants. If the masses are located in the pelvis adjacent to the iliac vessels, they may be confused with lymphadenopathy [5, 14, 30–33]. Moreover, some multiple, pedunculated leiomyomas arising from the uterus may mimic LPD implants. Final diagnosis relies on histological examination  and immunohistochemical evaluation.
Sometimes, LPD may recur in patients taking HRT [13, 24, 25] even after hysterectomy and bilateral salpingo-oophorectomy , or in patients who have undergone in vitro fertilization . Matthews and Speers reported a patient who died after a fourth recurrence of LPD and distant metastases 10 years after hysterectomy. Each recurrence seems to be more likely to produce morphological evidence of sarcoma .
Malignant transformation of LPD is uncommon and only ten cases have been documented in the English literature [8, 29]. Of these, only three occurred in postmenopausal women [29, 36]. The interval between initial detection of LPD and the development of sarcoma varies from synchronous diagnosis to 8 years. In most reports of malignant LPD, no history of oestrogen exposure was found. Bekkers hypothesized that LPD without exogenous or increased endogenous oestrogen exposure, and without expression of ER/PR by tumour cells, may represent a different entity carrying a higher risk of malignant transformation .
On the basis of these observations, we can affirm that no established guidelines exist regarding the management of LPD. However, therapy needs to be individualised according to the patient's age, hormonal and reproductive status and symptomatology. Different drugs (gonadotropin realising hormone agonist, megestrol acetate, danazol) have been considered in some cases but with poor results. If intestinal and bladder mass effect symptoms are prominent, a surgical approach is indicated .
We report a case of LPD diagnosed in a young lady who has never used oral contraceptives and was referred to our department because of pelvic pain, amenorrhoea, stress incontinence and chronic constipation. This case is unusual in the coexistence of this rare acquired condition with multiple congenital malformations, which had been diagnosed in our patient during her early life. A MEDLINE search of the English language literature revealed no report of associations between multiple malformations and LPD.
Most of the congenital malformations diagnosed in our patient seem to indicate a particular subgroup of the caudal regression syndrome (CRS): the Currarino syndrome (CS). CRS is a congenital heterogeneous constellation of caudal anomalies that include varying degrees of agenesis of the spinal column, anorectal malformations, genitourinary anomalies and pulmonary hypoplasia. The combination of hemisacrum, anorectal malformation (ARM), and presacral mass constitutes CS . The hemisacrum with its peculiar radiological aspect ("scimitar sign") is pathognomonic of CS [9, 38]. The most frequent type of ARM is the rectoperineal fistula, according to the Pena classification . The presacral tumour may be an anterior meningocoele (68%), a benign teratoma (18%), an enteric cyst, a dermoid cyst, a lipoma, hamartoma, or, rarely, a leimyosarcoma . Other associated anomalies in CS include tethering of the cord, hydrocephalus, duplex ureter, vesicoureteric reflux, hydronephrosis, neurogenic bladder, bicornuate uterus, rectovaginal fistula, hereditary spherocytosis, etc. [38, 41].
Currarino's syndrome is phenotypically very variable. It has been classified into three different types :
- Complete: full expression, presenting with hemisacrum, anorectal malformation and presacral mass;
- Mild: hemisacrum and only one of the other malformations (i.e. anorectal malformations or presacral mass);
- Minimal: only hemisacrum is present.
Girls are more commonly affected (80% of cases). Complete CS is commonly diagnosed in the first decade of life, whereas mild or minimal CS is diagnosed predominantly in adults [38, 42–44]. Genetically, CS is an autosomal dominant with incomplete penetrance. The gene responsible for the syndrome, HLXB9, has recently been mapped to the terminal portion of the long arm of chromosome 7 (7q36) [10, 11, 45]. It encodes a transcription factor expressed in the anterior horn regions of the spinal cord in human embryos. Mutational studies of the HLXB9 gene in a limited number of familial and sporadic CS patients have shown no obvious phenotype-genotype correlation [11, 45–47].
The absence of mutations within the coding sequence of the HLXB9 gene does not totally exclude the possibility that our patient might represent an atypical sporadic case of CS. First, the presence of hemisacrum, anorectal malformation, long-term chronic constipation and hydroureteronephrosis represent typical features of mild CS. Second, in contrast to the familial form of CS, in which almost all patients show mutations in the HLXB9 gene, mutations are much rarer in sporadic cases [45–47]. Mutations outside the coding region, partial deletions of the gene and especially genetic heterogeneity may contribute to this phenomenon . As previously reported, some CS cases carry hemizygous deletions of HLXB9. Since we lacked the facilities for microsatellite typing, we cannot exclude haploinsufficiency in our patient. Moreover, other candidate genes could be involved in sporadic CS cases; in particular, genes involved in the same pathways as HLXB9, such as ISL1 and LIM3, which were not investigated here .
Alternatively, since previous studies excluded the involvement of HLXB9 in CRS  and we failed to identify any HLXB9 mutation, we might more generally consider our patient to be a rare case of association between CRS and LPD.
The case we report is distinctive in that a rare acquired disease, LPD, coexists with multiple congenital malformations recalling a particular subgroup of the caudal regression syndrome: the Currarino syndrome (CS). Whether this association is coincidental or the expression of a common aetiopathogenetic mechanism remains to be ascertained.
Leiomyomatosis peritonealis disseminata
Caudal Regression Syndrome
Epithelial Membrane Antigen
Polymerase Chain Reaction
Hormone Replacement Therapy
- Enzinger SM, Weiss SW: Soft tissue tumours-text book. 1996, Mosby: New York, 479-483. 3Google Scholar
- Drake A, Dhundee J, Buckley CH, Woolas R: Disseminated leiomyomatosis peritonealis in association with ooestrogen secreting ovarian fibrothecoma. Brit J Obstet Gynaecol. 2001, 108: 661-664. 10.1016/S0306-5456(00)00132-7.Google Scholar
- Bekkers RL, Willemsen WN, Schijf CP, Massuger LF, Bulten J, Merkus JM: Leiomyomatosis peritonealis disseminata: does malignanttrasformation occur? A literature review. Gynecol Oncol. 1999, 75: 158-163. 10.1006/gyno.1999.5490.View ArticlePubMedGoogle Scholar
- Yamaguchi T, Imamura Y, Yamamoto T, Fukuda M: Leiomyomatosis peritonealis disseminata with malignant change in a man. Pathol Int. 2003, 53: 179-185. 10.1046/j.1440-1827.2003.01452.x.View ArticlePubMedGoogle Scholar
- Lausen I, Jensen OJ, Andersen E, Lindahl F: Disseminated peritoneal leiomyomatosis with malignant change, in a male. Virchows Arch A Pathol Anat Histopathol. 1990, 417: 173-5. 10.1007/BF02190536.View ArticlePubMedGoogle Scholar
- Herrero J, Kamali P, Kirschbaum M: Leiomyomatosis peritonealis disseminata associated with endometriosis: a case report and literature review. Eur J Obstet Gynecol Reprod Biol. 1998, 76: 189-191. 10.1016/S0301-2115(97)00173-5.View ArticlePubMedGoogle Scholar
- Hales HA, Peterson CM, Jones KP, Quinn JD: Leiomyomatsis peritonealis disseminata treated with a gonadotropin-releasing hormone agonist: a case report. Am J Obstet Gynecol. 1992, 167: 515-516.View ArticlePubMedGoogle Scholar
- Sharma P, Chaturvedi KU, Gupta R, Nigam S: Leiomyomatosis peritonealis disseminata with malignant change in a post-menopausal woman. Gynecol Oncol. 2004, 95: 742-745. 10.1016/j.ygyno.2004.09.007.View ArticlePubMedGoogle Scholar
- Currarino G, Coln D, Votteler T: Triad of anorectal, sacral, and presacral anomalies. AJR Am J Roentgenol. 1981, 137: 395-398.View ArticlePubMedGoogle Scholar
- Lynch SA, Bond PM, Copp AJ, Kirwan WO, Nour S, Balling R, Mariman E, Burn J, Strachan T: A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. Nat Genet. 1995, 11: 93-95. 10.1038/ng0995-93.View ArticlePubMedGoogle Scholar
- Ross AJ, Ruiz-Perez V, Wang Y, Hagan DM, Scherer S, Lynch SA, Lindsay S, Custard E, Belloni E, Wilson DI, Wadey R, Goodman F, Orstavik KH, Monclair T, Robson S, Reardon W, Burn J, Scambler P, Strachan T: A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998, 20: 358-361. 10.1038/3828.View ArticlePubMedGoogle Scholar
- Pang D: Sacral agenesis and caudal spinal cord malformations. Neurosurgery. 1993, 32: 755-779.View ArticlePubMedGoogle Scholar
- Nguyen K: Disseminated Leiomyomatosis peritonealis: report of a case in a postmenopausal woman. Canadian J Surg. 1993, 36: 46-48.Google Scholar
- Akkersdijk GJ, Flu PK, Giard RW, van Lent M, Wallenburg HC: Malignant leiomyomatosis peritonealis disseminata. Am J Obstet Gynecol. 1990, 163: 591-593.View ArticlePubMedGoogle Scholar
- Quade BJ, McLachlin CM, Wright VS, Zucherman J, Mutter GL, Morton CC: Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome inactivation and cytogenetics of a clinically benign smooth muscle proliferation. Am J Pathol. 1997, 150: 2153-2166.PubMedPubMed CentralGoogle Scholar
- Butnor KJ, Burchette JL, Robboy SJ: Progesterone receptor activity in leiomyomatosis peritonealis disseminata. Int J Gynecol Pathol. 1999, 18: 259-264.View ArticlePubMedGoogle Scholar
- Guarch R, Puras A, Ceres R, Isaac MA, Nogales FF: Ovarian endometriosis and clear cell carcinoma, leiomyomatosis peritonealis disseminata, and endometrial adenocarcinoma: an unusual, pathogenetically related association. Int J Gynecol Pathol. 2001, 20: 267-270. 10.1097/00004347-200107000-00010.View ArticlePubMedGoogle Scholar
- Bristow RE, Montz FJ: Leiomyomatosis peritonealis disseminata and ovarian Brenner tumour associated with tamoxifen use. Int J Gynecol Cancer. 2001, 11: 312-315. 10.1046/j.1525-1438.2001.011004312.x.View ArticlePubMedGoogle Scholar
- Dilts PV, Hopkins MP, Chang AE, Cody RL: Rapid growth of leiomyoma in patient receiving tamoxifen. Am J Obstet Gynecol. 1992, 166: 167-168.View ArticlePubMedGoogle Scholar
- Kang J, Baxi L, Heller D: Tamoxifen-induced growth of leiomyomas. A case report. J Reprod Med. 1996, 41: 119-120.PubMedGoogle Scholar
- Schwartz LB, Rutkowski N, Horan C, Nachtigall LE, Snyder J, Goldstein SR: Use of transvaginal ultrasonography to monitor the effects of tamoxifen on uterine leiomyoma size and ovarian cyst formation. J Ultrasound Med. 1998, 17: 699-703.PubMedGoogle Scholar
- Danikas D, Goudas VT, Rao CV, Brief DK: Luteinizing hormone receptor expression in leiomyomatosis peritonealis disseminata. Obstet Gynecol. 2000, 95: 1009-1011. 10.1016/S0029-7844(99)00587-6.PubMedGoogle Scholar
- Heinig J, Neff A, Cirkel U, Klockenbusch W: Recurrent leiomyomatosis peritonealis disseminata after hysterectomy and bilateral salpingo-oophorectomy during combined hormone replacement therapy. Eur J Obstet Gynecol Reprod Biol. 2003, 111: 216-218. 10.1016/S0301-2115(03)00237-9.View ArticlePubMedGoogle Scholar
- Rajab KE, Aradi AN, Datta BN: Postmenopausal leimyomatosis peritonealis disseminata. Int J Gynaecol Obstet. 2000, 68: 271-272. 10.1016/S0020-7292(99)00203-9.View ArticlePubMedGoogle Scholar
- Strinic T, Kuzmic-Prusac I, Eterovic D, Jakic J, Scukanec M: Leiomyomatosis peritonealis disseminata in a postmenopausal woman. Arch Gynecol Obstet. 2000, 264: 97-98. 10.1007/s004040000070.View ArticlePubMedGoogle Scholar
- Halama N, Grauling-Halama SA, Daboul I: Familial clustering of Leiomyomatosis peritonealis disseminata: an unknown genetic syndrome?. BMC Gastroenterol. 2005, 13: 33-10.1186/1471-230X-5-33.View ArticleGoogle Scholar
- Zhu L, Li B: Clinico-pathologic study of leiomyomatosis peritonealis disseminate. Zhonghua Bing Li Xue Za Zhi. 1996, 25: 270-272.PubMedGoogle Scholar
- Buckshee K, Verma A, Karak AK: Leiomyomatosis peritonealis disseminata. Int J Gynaecol Obstet. 1998, 61: 191-192. 10.1016/S0020-7292(98)00046-0.View ArticlePubMedGoogle Scholar
- Fulcher AS, Szucs RA: Leiomyomatosis peritonealis disseminata complicated by sarcomatous transformation and ovarian torsion: presentation of two cases and review of the literature. Abdom Imaging. 1998, 23: 640-644. 10.1007/s002619900421.View ArticlePubMedGoogle Scholar
- Bourgain C, Pierre E, De Vits A, Amy JJ, Kloppel G: Disseminated peritoneal leiomyomatosis. An unusual case. Pathol Res Pract. 1994, 190: 500-504.View ArticlePubMedGoogle Scholar
- Kokcu A, Alvur Y, Baris YS, Kuskonmaz I: Leiomyomatosis peritonealis disseminata. Acta Obstet Gynecol. 1994, 73: 81-83.View ArticleGoogle Scholar
- Papadatos D, Taourel P, Bret PM: CT of leiomyomatosis peritonealis disseminata mimicking peritoneal carcinomatosis. AJR. 1996, 167: 475-476.View ArticlePubMedGoogle Scholar
- Abulafia O, Angel C, Sherer DM, Fultz PJ, Bonfiglio TA, DuBeshter B: Computed tomography of leiomyomatosis peritonealis disseminata with malignant transformation. Am J Obstet Gynecol. 1993, 169: 52-54.View ArticlePubMedGoogle Scholar
- Nogales FF, Matilla A, Carrascal E: Leiomyomatosis peritonealis disseminata. An ultrastructural study. Am J Clin Pathol. 1978, 69: 452-457.View ArticlePubMedGoogle Scholar
- Deering S, Miller B, Kopelman JN, Reed M: Recurrent leiomyomatosis peritonealis disseminata exacerbated by in vitro fertilization. Am J Obstet Gynecol. 2000, 182: 725-726. 10.1067/mob.2000.101978.View ArticlePubMedGoogle Scholar
- Raspagliesi F, Quattrone P, Grosso G, Cobellis L, Di Re E: Malignant degeneration in leiomyomatosis peritonealis disseminata. Gynecol Oncol. 1996, 61: 272-274. 10.1006/gyno.1996.0138.View ArticlePubMedGoogle Scholar
- Ghosh K, Dorigo O, Bristow R, Berek J: A radical debulking of leiomyomatosis peritonealis disseminata from a colonic obstruction: a case report and review of the literature. J Am Coll Surg. 2000, 191: 212-215. 10.1016/S1072-7515(00)00350-1.View ArticlePubMedGoogle Scholar
- Martucciello G, Torre M, Belloni E, Lerone M, Pini Prato A, Cama A, Jasonni V: Currarino sindrome: proposal of a diagnostic and therapeutic protocol. J Pediatr Surg. 2004, 39: 1305-1311. 10.1016/j.jpedsurg.2004.05.003.View ArticlePubMedGoogle Scholar
- Pena A: Anorectal malformations. Semin Pediatr Surg. 1995, 4: 35-37.PubMedGoogle Scholar
- Baltogiannis N, Mavridis G, Soutis M, Keramidas D: Currarino triad associated with Hirschsprung's disease. J Pediatr Surg. 2003, 38: 1086-1089. 10.1016/S0022-3468(03)00199-4.View ArticlePubMedGoogle Scholar
- O'Riordain DS, O'Connell PR, Kirwan WO: Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. Br J Surg. 1991, 78: 536-538.View ArticlePubMedGoogle Scholar
- Kenefick JS: Hereditary sacral agenesis associated with presacral tumours. Br J Surg. 1973, 60: 271-274.View ArticlePubMedGoogle Scholar
- Norum J, Wist E, Bostad L: Incomplete Currarino syndrome with a presacral leiomyosarcoma. Acta Oncol. 1991, 30: 987-988.View ArticlePubMedGoogle Scholar
- Tamayo JA, Arraez MA, Villegas I, Ruiz J, Rodriguez E, Fernandez O: Partial Currarino syndrome in a non-pediatric patient. A rare cause of bacterial meningitis. Neurologia. 1999, 14: 460-462.PubMedGoogle Scholar
- Belloni E, Martucciello G, Verderio D, Ponti E, Seri M, Jasonni V, et al: Involvement of the HLXB9 homeobox gene in Currarino syndrome. Am J Hum Genet. 2000, 66: 312-319. 10.1086/302723.View ArticlePubMedPubMed CentralGoogle Scholar
- Hagan DM, Ross AJ, Strachan T, Lynch SA, Ruiz-Perez V, Wang YM, et al: Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene. Am J Hum Genet. 2000, 66: 1504-1515. 10.1086/302899.View ArticlePubMedPubMed CentralGoogle Scholar
- Kochling J, Karbasiyan M, Reis A: Spectrum of mutations and genotype-phenotype analysis in Currarino syndrome. Eur J Hum Genet. 2001, 9: 599-605. 10.1038/sj.ejhg.5200683.View ArticlePubMedGoogle Scholar
- Merello E, De Marco P, Mascelli S, Raso A, Calevo MG, Torre M, Cama A, Lerone M, Martucciello G, Capra V: HLXB9 homeobox gene and caudal regression syndrome. Birth Defects Res A Clin Mol Teratol. 2006, 23:Google Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/127/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.