Novel Insights from Clinical Practice Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
Received: June 25, 2014 Accepted after revision: October 2, 2014 Published online: February 25, 2015
Pediatric Glioblastoma Multiforme in Association with Turner’s Syndrome: A Case Report Sara Hanaei a Zohreh Habibi a Farideh Nejat a Fatemeh Sayarifard b Mohammad Vasei c Departments of a Neurosurgery and b Pediatric Endocrinology, Children’s Hospital Medical Center, and c Department of Pathology, Digestive and Liver Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Established Facts • The Ullrich-Turner syndrome is associated with a tendency to develop gonadogenic tumors. • Some extragonadal neoplasms have been sporadically reported in Turner’s syndrome, suggesting an increased risk of oncogenesis in this syndrome.
Novel Insights • An unprecedented case of ‘primary pediatric glioblastoma multiforme’ in a child with ‘Turner’s syndrome’ is represented. • Turner’s syndrome can be supposed to be associated with some neurogenic tumors, including pediatric glioblastoma multiforme.
Abstract The Ullrich-Turner syndrome (complete or partial X-chromosome monosomy) has been found to be associated with an increased rate of some extragonadal neoplasms. Sporadic reports of the Turner syndrome with various brain tumors, including few cases of glioblastoma multiforme, have been
© 2015 S. Karger AG, Basel 1016–2291/15/0501–0038$39.50/0 E-Mail [email protected] www.karger.com/pne
found in the literature. However, published data are insufficient to establish a definite relationship between these tumors and the Turner syndrome. Herein, a rare case of primary pediatric glioblastoma multiforme in a 7-year-old girl with Turner’s syndrome is reported, and various aspects regarding clinical and pathophysiological issues have been discussed. Although Turner’s syndrome is not one of the congenital chromosomal abnormalities which demand routine CNS screening, neurological assessment may be of value in those with relevant clinical findings. © 2015 S. Karger AG, Basel
Zohreh Habibi Department of Neurosurgery, Children’s Hospital Medical Center Tehran University of Medical Sciences 62, Gharib Street, Keshavarz Boulevard, Tehran 1419733151 (Iran) E-Mail Zohreh_h56 @ yahoo.com
Downloaded by: University of Pittsburgh 198.143.32.65 - 8/13/2015 11:32:36 PM
Key Words Turner’s syndrome · Glioblastoma multiforme · Neurooncology · Pediatric brain tumors
Glioblastoma multiforme (GBM) is a clinically and genetically heterogeneous highly malignant brain tumor, which is extremely rare in children compared with the adult population [1]. Few cases of either primary or secondary GBM in Turner’s syndrome (TS) have been reported. However, the data are insufficient to draw any conclusion regarding the risk of GBM in TS patients. Herein, we report a rare case of primary pediatric GBM in a 7-year-old girl with short stature who was ultimately diagnosed with TS. To the best of our knowledge, this is the first report of GBM in a child with TS; few cases were previously reported in adults with TS.
Histopathological examination revealed a highly cellular glial tumor with diffuse area of necrosis adjacent to tumor cells, high pleomorphism and marked anaplasia with giant cell formation, which was compatible with a diagnosis of GBM (fig. 2). Immunohistochemical staining was not needed since histopathological evidence revealed enough typical pathognomonic findings to confirm the GBM diagnosis. The patient was discharged home after 1 week and was scheduled for chemo-radiotherapy 1 month after surgery.
Discussion
Operation Under general anesthesia and in supine position, a tailored craniotomy was performed and a highly vascular tumor with soft consistency was totally resected. The postoperative period was uneventful and the patient was discharged from the intensive care unit without any neurological sequelae after 24 h.
The Ullrich-Turner syndrome or TS, a cytogenetic condition affecting only females, is characterized by complete or partial X-chromosome monosomy [2]. This syndrome occurs 1 in 2,000–3,500 live-born girls and is, in fact, the most common chromosomal abnormality in females [2, 3]. The phenotype usually includes webbed neck, a low posterior hairline, cubitus valgus, short stature and lymphedema [4]. The syndrome is commonly associated with hypergonadotropic hypogonadism due to poorly functioning gonads [5]; a wide range of clinical abnormalities, including cardiac and renal anomalies, may also be found [6]. In patients without pathognomonic clinical features in infancy, the diagnosis may be missed because of a normal phenotype. Furthermore, interpretation of the karyotype responsible for the individual phenotypic expression is very difficult because of mosaicism and, in fact, there is no correlation between the relative number of various cell types and the ultimate phenotype [7]. The patient may have no phenotypic abnormalities other than a short stature, which was also the case in our patient. The risk for neoplastic diseases is increased in some congenital chromosome abnormalities, e.g. Down’s syndrome, 13q syndrome and Klinefelter’s syndrome [7]. Although a tendency to develop gonadogenic tumors has been suggested in TS [3], extragonadal neoplasms such as various neural crest, gastrointestinal and hematologic cancers have also been reported sporadically [4, 8]. A national cohort of women with TS in Great Britain has shown a probably increased risk for bladder cancer, melanoma, uterine corpus cancer, meningioma and childhood brain tumors [2]. Neurogenic tumors have been considered to be the most common nongonadal neoplasms in TS, especially in the pediatric population [3]. Sporadic reports of various neurogenic tumors, such as neuroblastoma, ganglioneuroblastoma, retinoblastoma, malignant melanoma, medulloblastoma, glioma, oligodendroglioma, pheochromocytoma, schwanomma, me-
Glioblastoma Multiforme in Turner’s Syndrome
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
Case Presentation History and Examination A 7-year-old girl, the firstborn child of a nonconsanguineous marriage, presented with short stature together with headache and vomiting since the past few days. She was referred to the Children’s Hospital Medical Center for workup of short stature. Her birth length was 49 cm and her birth weight 2,400 g, which were within the 50th and 3rd percentiles, respectively. Her development was normal since 3 years of age. The patient’s younger sister had normal development from birth without short stature. The family had neither a history of short stature nor of central nervous system (CNS) malignancies in 1st- to 3rd-degree relatives. On admission, her height and weight were 106 cm (mean: 120.8 ± 5.46 cm) and 19.5 kg (mean: 22.4 ± 3.5 kg), which were under the 1st percentile and between the 15th and 25th percentiles, respectively. Genitalia appearance seemed normal and endocrine tests were within the normal range. Based on left-hand and wrist radiographs, her bone age was estimated to be 1 year behind the chronological age. During evaluations for short stature, a saliva test was negative for Barr bodies, and a subsequent genetic investigation revealed a 45 XO karyotype, which confirmed the diagnosis of TS. Deterioration of headache and vomiting led us to perform a neuroimaging study. Brain computed tomography surprisingly showed a space-occupying lesion in the left frontoparietal lobe. Magnetic resonance imaging (MRI) revealed a solid cystic mass lesion concomitant with vasogenic edema and mass effect with hyperintense appearance on T2-weighted sequences (fig. 1a) and a marked heterogeneous enhancement in T1-weighted images following gadolinium injection (fig. 1b, c). Nonetheless, no neurological deficit was found clinically.
39
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Introduction
a
c
b
a
ningioma, craniopharyngioma, primary pituitary adenoma and pituitary hyperplasia due to hypogonadism have been described in the literature [2, 3, 5, 7, 9–13]. However, published data are too few to establish a definite relationship [4]. Potential associations of CNS tumors with TS have been mostly attributed to an increased risk of meningioma, especially in those treated with growth hormone. Even so, pediatric GBM in TS has been rarely reported. We found only two reports of GBM in patients with TS; one in an adult female with multiple nongonadal cancers [7] and the other in a 36-year-old female who developed malignant progression of an earlier anaplastic ganglioglioma [14]. Here, we report a case of primary GBM in a child with TS. The risk of oncogenesis in TS might be related to hormonal factors or the effects of hormonal treatments, which can affect the risk of hormone-related cancers. Although treatment with growth hormone has been corre40
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
b
lated with cancerous lesions in TS children, our patient was not treated with growth hormone before tumor presentation. Further, the chromosomal abnormality itself might affect the risk of cancer. Investigations suggested that the chromosomally abnormal clone was more prone to undergo neoplastic transformation than cytogenetically normal cells [7]. The cancer risks in TS could be potentially correlated to the absence of one or more tumor suppressor genes on the X chromosome [15]. It is possible that TS (first hit) unmasks an abnormality in an X-linked tumor suppressor gene (second hit) [4]. Analyses showed the risk of CNS tumors to be higher in classic 45 XO monosomy (classic TS) than mosaic groups [2], a finding supporting the possible role of monoallelic expression of X-linked genes in tumor formation. Besides, some chromosomal abnormalities which increase the risk of CNS cancers have been occasionally reported in TS. For instance, a deletion on exon 9 of the NF2 gene has been detected in a case of TS with rhabdoid meningioma [11], Hanaei/Habibi/Nejat/Sayarifard/Vasei
Downloaded by: University of Pittsburgh 198.143.32.65 - 8/13/2015 11:32:36 PM
Fig. 2. Diffuse area of necrosis (left) is seen adjacent to tumor cells with high pleomorphism (right). HE. ×250 (a). Marked anaplasia with giant cell formation is noted. HE. ×400 (b).
Color version available online
Fig. 1. T2-weighted MRI reveals a hyperintense solid-cystic mass lesion in the left frontoparietal region accompanied with vasogenic edema and mass effect (a). T1-weighted images after gadolinium injection show marked heterogeneous enhancement of the lesion (b, c).
and a case of TS with ganglioneuroblastoma was diagnosed with germline p53 mutation (Li-Fraumeni syndrome). Rare associations of TS with neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex have been reported, too [6, 16]. Knowledge about the association of CNS tumors with TS is important in terms of counseling parents on disease prognostic implications, and regarding clinical and screening practice during the follow-up of these patients [2]. No screening program has been proposed for TS patients so far, and it is not clear if such a program would improve survival and quality of life. Although routine neuroimaging studies should not be performed in all TS patients, we recommend it in patients with neurological symptoms including headache, seizure and focal neurological deficits. Also, each patient with Turner-like symptoms should be carefully examined for café-au-lait macules and NF-1 phenotypic traits; on the other hand,
chromosome studies should be performed in girls with NF-1 who have short stature and a Ullrich-Turner-like phenotype [17].
Conclusion
Although the exact risk of oncogenesis in TS is not well established, there are some reports of neurogenic tumors in patients with TS. TS is not among the congenital chromosomal abnormalities which demand routine CNS screening, but neurological assessment may be of value in those with relevant clinical findings. Disclosure Statement There was no source of extra-institutional funding in this work, and none of the authors has any potential conflict of interest.
References
Glioblastoma Multiforme in Turner’s Syndrome
6 Hatipoglu N, Kurtoglu S, Kendirci M, Keskin M, Per H: Neurofibromatosis type 1 with overlap Turner syndrome and Klinefelter syndrome. J Trop Pediatr 2010;56:69–72. 7 Ochi H, Takeuchi J, Sandberg AA: Multiple cancers in a Turner’s syndrome with 45,X/ 46,XXp-/46,XX/47,XXX karyotype. Cancer Genet Cytogenet 1985;16:335–339. 8 Tang WJ, Huang Y, Chen L, Zheng S, Dong KR: Small intestinal tubular adenoma in a pediatric patient with Turner syndrome. World J Gastroenterol 2013;19:2122–2125. 9 Farooque A, Atapattu N, Amarasena S, Högler W, English MW, Kirk JM: An association of craniopharyngioma in Turner syndrome. Pediatr Blood Cancer 2013;60:E7–E9. 10 Pendergrass TW, Fraumeni JF Jr: Brain tumors in sibs, one with the Turner syndrome (letter). J Pediatr 1974;85:875. 11 Nozza P, Raso A, Rossi A, Milanaccio C, Pezzolo A, Capra V, Gambini C, Pietsch T: Rhabdoid meningioma of the tentorium with expression of desmin in a 12-year-old Turner syndrome patient. Acta Neuropathol 2005; 110:205–206. 12 Yamazaki M, Sato A, Nishio S, Takeda T, Miyamoto T, Katai M, Hashizume K: Acromegaly accompanied by Turner syndrome with 47,XXX/45,X/46,XX mosaicism. Intern Med 2009;48:447–453.
13 Samaan NA, Stepanas AV, Danziger J, Trujillo J: Reactive pituitary abnormalities in patients with Klinefelter’s and Turner’s syndromes. Arch Intern Med 1979; 139: 198– 201. 14 Naydenov E, Tzekov C, Minkin K, Nachev S: Malignant progression of anaplastic supratentorial ganglioglioma into glioblastoma multiforme in a patient with Turner syndrome. J Neurol Surg A Cent Eur Neurosurg 2012;73:253–255. 15 Wang MG, Zakut R, Yi H, Rosenberg S, McBride OW: Localization of the MAGE1 gene encoding a human melanoma antigen to chromosome Xq28. Cytogenet Cell Genet 1994;67:116–119. 16 S Suttur M, R Mysore S, Krishnamurthy B, B Nallur R: Rare association of Turner syndrome with neurofibromatosis type 1 and tuberous sclerosis complex. Indian J Hum Genet 2009;15:75–77. 17 Schorry EK, Lovell AM, Milatovich A, Saal HM: Ullrich-Turner syndrome and eurofibromatosis-1. Am J Med Genet 1996;66:423– 425.
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
41
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1 Borkar SA, Lakshmiprasad G, Subbarao KC, Sharma MC, Mahapatra AK: Giant cell glioblastoma in the pediatric age group: report of two cases. J Pediatr Neurosci 2013;8:38–40. 2 Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA: Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol 2008;9:239–246. 3 Chen SH, Hung CS, Lo FS, Wang HS, Jung SM, Lui TN: Primitive neuroectodermal tumor of the brain in a girl with Turner syndrome diagnosed after 4 years of growth hormone therapy. Eur J Pediatr 2006; 165: 344– 345. 4 Pivnick EK, Furman WL, Velagaleti GVN, Jenkins JJ, Chase NA, Ribeiro RC: Simultaneous adrenocortical carcinoma and ganglioneuroblastoma in a child with Turner syndrome and germline p53 mutation. J Med Genet 1998;35:328–332. 5 Dötscha J, Schoofa E, Hensenb J, Dörra HG: Prolactinoma causing secondary amenorrhea in a woman with Ullrich-Turner syndrome. Horm Res 1999;51:256–257.
Received: June 25, 2014 Accepted after revision: October 2, 2014 Published online: February 25, 2015
Pediatric Glioblastoma Multiforme in Association with Turner’s Syndrome: A Case Report Sara Hanaei a Zohreh Habibi a Farideh Nejat a Fatemeh Sayarifard b Mohammad Vasei c Departments of a Neurosurgery and b Pediatric Endocrinology, Children’s Hospital Medical Center, and c Department of Pathology, Digestive and Liver Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Established Facts • The Ullrich-Turner syndrome is associated with a tendency to develop gonadogenic tumors. • Some extragonadal neoplasms have been sporadically reported in Turner’s syndrome, suggesting an increased risk of oncogenesis in this syndrome.
Novel Insights • An unprecedented case of ‘primary pediatric glioblastoma multiforme’ in a child with ‘Turner’s syndrome’ is represented. • Turner’s syndrome can be supposed to be associated with some neurogenic tumors, including pediatric glioblastoma multiforme.
Abstract The Ullrich-Turner syndrome (complete or partial X-chromosome monosomy) has been found to be associated with an increased rate of some extragonadal neoplasms. Sporadic reports of the Turner syndrome with various brain tumors, including few cases of glioblastoma multiforme, have been
© 2015 S. Karger AG, Basel 1016–2291/15/0501–0038$39.50/0 E-Mail [email protected] www.karger.com/pne
found in the literature. However, published data are insufficient to establish a definite relationship between these tumors and the Turner syndrome. Herein, a rare case of primary pediatric glioblastoma multiforme in a 7-year-old girl with Turner’s syndrome is reported, and various aspects regarding clinical and pathophysiological issues have been discussed. Although Turner’s syndrome is not one of the congenital chromosomal abnormalities which demand routine CNS screening, neurological assessment may be of value in those with relevant clinical findings. © 2015 S. Karger AG, Basel
Zohreh Habibi Department of Neurosurgery, Children’s Hospital Medical Center Tehran University of Medical Sciences 62, Gharib Street, Keshavarz Boulevard, Tehran 1419733151 (Iran) E-Mail Zohreh_h56 @ yahoo.com
Downloaded by: University of Pittsburgh 198.143.32.65 - 8/13/2015 11:32:36 PM
Key Words Turner’s syndrome · Glioblastoma multiforme · Neurooncology · Pediatric brain tumors
Glioblastoma multiforme (GBM) is a clinically and genetically heterogeneous highly malignant brain tumor, which is extremely rare in children compared with the adult population [1]. Few cases of either primary or secondary GBM in Turner’s syndrome (TS) have been reported. However, the data are insufficient to draw any conclusion regarding the risk of GBM in TS patients. Herein, we report a rare case of primary pediatric GBM in a 7-year-old girl with short stature who was ultimately diagnosed with TS. To the best of our knowledge, this is the first report of GBM in a child with TS; few cases were previously reported in adults with TS.
Histopathological examination revealed a highly cellular glial tumor with diffuse area of necrosis adjacent to tumor cells, high pleomorphism and marked anaplasia with giant cell formation, which was compatible with a diagnosis of GBM (fig. 2). Immunohistochemical staining was not needed since histopathological evidence revealed enough typical pathognomonic findings to confirm the GBM diagnosis. The patient was discharged home after 1 week and was scheduled for chemo-radiotherapy 1 month after surgery.
Discussion
Operation Under general anesthesia and in supine position, a tailored craniotomy was performed and a highly vascular tumor with soft consistency was totally resected. The postoperative period was uneventful and the patient was discharged from the intensive care unit without any neurological sequelae after 24 h.
The Ullrich-Turner syndrome or TS, a cytogenetic condition affecting only females, is characterized by complete or partial X-chromosome monosomy [2]. This syndrome occurs 1 in 2,000–3,500 live-born girls and is, in fact, the most common chromosomal abnormality in females [2, 3]. The phenotype usually includes webbed neck, a low posterior hairline, cubitus valgus, short stature and lymphedema [4]. The syndrome is commonly associated with hypergonadotropic hypogonadism due to poorly functioning gonads [5]; a wide range of clinical abnormalities, including cardiac and renal anomalies, may also be found [6]. In patients without pathognomonic clinical features in infancy, the diagnosis may be missed because of a normal phenotype. Furthermore, interpretation of the karyotype responsible for the individual phenotypic expression is very difficult because of mosaicism and, in fact, there is no correlation between the relative number of various cell types and the ultimate phenotype [7]. The patient may have no phenotypic abnormalities other than a short stature, which was also the case in our patient. The risk for neoplastic diseases is increased in some congenital chromosome abnormalities, e.g. Down’s syndrome, 13q syndrome and Klinefelter’s syndrome [7]. Although a tendency to develop gonadogenic tumors has been suggested in TS [3], extragonadal neoplasms such as various neural crest, gastrointestinal and hematologic cancers have also been reported sporadically [4, 8]. A national cohort of women with TS in Great Britain has shown a probably increased risk for bladder cancer, melanoma, uterine corpus cancer, meningioma and childhood brain tumors [2]. Neurogenic tumors have been considered to be the most common nongonadal neoplasms in TS, especially in the pediatric population [3]. Sporadic reports of various neurogenic tumors, such as neuroblastoma, ganglioneuroblastoma, retinoblastoma, malignant melanoma, medulloblastoma, glioma, oligodendroglioma, pheochromocytoma, schwanomma, me-
Glioblastoma Multiforme in Turner’s Syndrome
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
Case Presentation History and Examination A 7-year-old girl, the firstborn child of a nonconsanguineous marriage, presented with short stature together with headache and vomiting since the past few days. She was referred to the Children’s Hospital Medical Center for workup of short stature. Her birth length was 49 cm and her birth weight 2,400 g, which were within the 50th and 3rd percentiles, respectively. Her development was normal since 3 years of age. The patient’s younger sister had normal development from birth without short stature. The family had neither a history of short stature nor of central nervous system (CNS) malignancies in 1st- to 3rd-degree relatives. On admission, her height and weight were 106 cm (mean: 120.8 ± 5.46 cm) and 19.5 kg (mean: 22.4 ± 3.5 kg), which were under the 1st percentile and between the 15th and 25th percentiles, respectively. Genitalia appearance seemed normal and endocrine tests were within the normal range. Based on left-hand and wrist radiographs, her bone age was estimated to be 1 year behind the chronological age. During evaluations for short stature, a saliva test was negative for Barr bodies, and a subsequent genetic investigation revealed a 45 XO karyotype, which confirmed the diagnosis of TS. Deterioration of headache and vomiting led us to perform a neuroimaging study. Brain computed tomography surprisingly showed a space-occupying lesion in the left frontoparietal lobe. Magnetic resonance imaging (MRI) revealed a solid cystic mass lesion concomitant with vasogenic edema and mass effect with hyperintense appearance on T2-weighted sequences (fig. 1a) and a marked heterogeneous enhancement in T1-weighted images following gadolinium injection (fig. 1b, c). Nonetheless, no neurological deficit was found clinically.
39
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Introduction
a
c
b
a
ningioma, craniopharyngioma, primary pituitary adenoma and pituitary hyperplasia due to hypogonadism have been described in the literature [2, 3, 5, 7, 9–13]. However, published data are too few to establish a definite relationship [4]. Potential associations of CNS tumors with TS have been mostly attributed to an increased risk of meningioma, especially in those treated with growth hormone. Even so, pediatric GBM in TS has been rarely reported. We found only two reports of GBM in patients with TS; one in an adult female with multiple nongonadal cancers [7] and the other in a 36-year-old female who developed malignant progression of an earlier anaplastic ganglioglioma [14]. Here, we report a case of primary GBM in a child with TS. The risk of oncogenesis in TS might be related to hormonal factors or the effects of hormonal treatments, which can affect the risk of hormone-related cancers. Although treatment with growth hormone has been corre40
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
b
lated with cancerous lesions in TS children, our patient was not treated with growth hormone before tumor presentation. Further, the chromosomal abnormality itself might affect the risk of cancer. Investigations suggested that the chromosomally abnormal clone was more prone to undergo neoplastic transformation than cytogenetically normal cells [7]. The cancer risks in TS could be potentially correlated to the absence of one or more tumor suppressor genes on the X chromosome [15]. It is possible that TS (first hit) unmasks an abnormality in an X-linked tumor suppressor gene (second hit) [4]. Analyses showed the risk of CNS tumors to be higher in classic 45 XO monosomy (classic TS) than mosaic groups [2], a finding supporting the possible role of monoallelic expression of X-linked genes in tumor formation. Besides, some chromosomal abnormalities which increase the risk of CNS cancers have been occasionally reported in TS. For instance, a deletion on exon 9 of the NF2 gene has been detected in a case of TS with rhabdoid meningioma [11], Hanaei/Habibi/Nejat/Sayarifard/Vasei
Downloaded by: University of Pittsburgh 198.143.32.65 - 8/13/2015 11:32:36 PM
Fig. 2. Diffuse area of necrosis (left) is seen adjacent to tumor cells with high pleomorphism (right). HE. ×250 (a). Marked anaplasia with giant cell formation is noted. HE. ×400 (b).
Color version available online
Fig. 1. T2-weighted MRI reveals a hyperintense solid-cystic mass lesion in the left frontoparietal region accompanied with vasogenic edema and mass effect (a). T1-weighted images after gadolinium injection show marked heterogeneous enhancement of the lesion (b, c).
and a case of TS with ganglioneuroblastoma was diagnosed with germline p53 mutation (Li-Fraumeni syndrome). Rare associations of TS with neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex have been reported, too [6, 16]. Knowledge about the association of CNS tumors with TS is important in terms of counseling parents on disease prognostic implications, and regarding clinical and screening practice during the follow-up of these patients [2]. No screening program has been proposed for TS patients so far, and it is not clear if such a program would improve survival and quality of life. Although routine neuroimaging studies should not be performed in all TS patients, we recommend it in patients with neurological symptoms including headache, seizure and focal neurological deficits. Also, each patient with Turner-like symptoms should be carefully examined for café-au-lait macules and NF-1 phenotypic traits; on the other hand,
chromosome studies should be performed in girls with NF-1 who have short stature and a Ullrich-Turner-like phenotype [17].
Conclusion
Although the exact risk of oncogenesis in TS is not well established, there are some reports of neurogenic tumors in patients with TS. TS is not among the congenital chromosomal abnormalities which demand routine CNS screening, but neurological assessment may be of value in those with relevant clinical findings. Disclosure Statement There was no source of extra-institutional funding in this work, and none of the authors has any potential conflict of interest.
References
Glioblastoma Multiforme in Turner’s Syndrome
6 Hatipoglu N, Kurtoglu S, Kendirci M, Keskin M, Per H: Neurofibromatosis type 1 with overlap Turner syndrome and Klinefelter syndrome. J Trop Pediatr 2010;56:69–72. 7 Ochi H, Takeuchi J, Sandberg AA: Multiple cancers in a Turner’s syndrome with 45,X/ 46,XXp-/46,XX/47,XXX karyotype. Cancer Genet Cytogenet 1985;16:335–339. 8 Tang WJ, Huang Y, Chen L, Zheng S, Dong KR: Small intestinal tubular adenoma in a pediatric patient with Turner syndrome. World J Gastroenterol 2013;19:2122–2125. 9 Farooque A, Atapattu N, Amarasena S, Högler W, English MW, Kirk JM: An association of craniopharyngioma in Turner syndrome. Pediatr Blood Cancer 2013;60:E7–E9. 10 Pendergrass TW, Fraumeni JF Jr: Brain tumors in sibs, one with the Turner syndrome (letter). J Pediatr 1974;85:875. 11 Nozza P, Raso A, Rossi A, Milanaccio C, Pezzolo A, Capra V, Gambini C, Pietsch T: Rhabdoid meningioma of the tentorium with expression of desmin in a 12-year-old Turner syndrome patient. Acta Neuropathol 2005; 110:205–206. 12 Yamazaki M, Sato A, Nishio S, Takeda T, Miyamoto T, Katai M, Hashizume K: Acromegaly accompanied by Turner syndrome with 47,XXX/45,X/46,XX mosaicism. Intern Med 2009;48:447–453.
13 Samaan NA, Stepanas AV, Danziger J, Trujillo J: Reactive pituitary abnormalities in patients with Klinefelter’s and Turner’s syndromes. Arch Intern Med 1979; 139: 198– 201. 14 Naydenov E, Tzekov C, Minkin K, Nachev S: Malignant progression of anaplastic supratentorial ganglioglioma into glioblastoma multiforme in a patient with Turner syndrome. J Neurol Surg A Cent Eur Neurosurg 2012;73:253–255. 15 Wang MG, Zakut R, Yi H, Rosenberg S, McBride OW: Localization of the MAGE1 gene encoding a human melanoma antigen to chromosome Xq28. Cytogenet Cell Genet 1994;67:116–119. 16 S Suttur M, R Mysore S, Krishnamurthy B, B Nallur R: Rare association of Turner syndrome with neurofibromatosis type 1 and tuberous sclerosis complex. Indian J Hum Genet 2009;15:75–77. 17 Schorry EK, Lovell AM, Milatovich A, Saal HM: Ullrich-Turner syndrome and eurofibromatosis-1. Am J Med Genet 1996;66:423– 425.
Pediatr Neurosurg 2014–15;50:38–41 DOI: 10.1159/000368804
41
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1 Borkar SA, Lakshmiprasad G, Subbarao KC, Sharma MC, Mahapatra AK: Giant cell glioblastoma in the pediatric age group: report of two cases. J Pediatr Neurosci 2013;8:38–40. 2 Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA: Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol 2008;9:239–246. 3 Chen SH, Hung CS, Lo FS, Wang HS, Jung SM, Lui TN: Primitive neuroectodermal tumor of the brain in a girl with Turner syndrome diagnosed after 4 years of growth hormone therapy. Eur J Pediatr 2006; 165: 344– 345. 4 Pivnick EK, Furman WL, Velagaleti GVN, Jenkins JJ, Chase NA, Ribeiro RC: Simultaneous adrenocortical carcinoma and ganglioneuroblastoma in a child with Turner syndrome and germline p53 mutation. J Med Genet 1998;35:328–332. 5 Dötscha J, Schoofa E, Hensenb J, Dörra HG: Prolactinoma causing secondary amenorrhea in a woman with Ullrich-Turner syndrome. Horm Res 1999;51:256–257.
