- Email: [email protected]
Tremor and Deep Brain Nuclei Hyperintensities in Kabuki Syndrome
Tremor and Deep Brain Nuclei Hyperintensities in Kabuki Syndrome Christopher Grunseich, MD*, Thomas M. Fishbein, MD†, Frank Berkowitz, MD‡, and Ejaz A. Shamim, MD, MS*§ Kabuki syndrome is a rare congenital disorder first described in 1981. Case reports indicate multiple congenital abnormalities: skeletal anomalies, cognitive impairment, characteristic facial appearance, and peculiar dermatoglyphic patterns. We describe a patient with Kabuki syndrome who presented with physiologic tremor in her distal upper extremities. Cranial magnetic resonance imaging revealed symmetric T2-hyperintense lesions with mildly restricted diffusion in the lentiform nuclei, red nuclei, and dentate nuclei bilaterally. Although multiple abnormalities of the central nervous system were reported previously in Kabuki syndrome, this patient is the first, to the best of our knowledge, with the unique findings that we observed. Ó 2010 by Elsevier Inc. All rights reserved. Grunseich C, Fishbein TM, Berkowitz F, Shamim EA. Tremor and deep brain nuclei hyperintensities in Kabuki syndrome. Pediatr Neurol 2010;43:148-150.
Introduction Kabuki (makeup) syndrome was first described in a Japanese patient population by Niikawa et al. [1]. Patients with Kabuki syndrome manifest multiple congenital abnormalities, including characteristic facies with long palpebral fissures, eversion of the lower lateral eyelids, enlarged ears,
and depressed nasal tips. The cause remains unknown, and although several genetic loci were previously investigated, the causative genetic loci remain unidentified. In addition to the classic facial findings, patients with Kabuki syndrome also manifest characteristic skeletal abnormalities, short stature, abnormal dentition, and other visceral anomalies that may necessitate organ transplants [2]. Multiple abnormalities of the central nervous system were also reported, including Chiari I malformation [3], agenesis of the corpus callosum and atrophy of the hippocampus [4], and central hypoplasia [5]. Several clinical neurologic findings were also reported in patients with Kabuki syndrome, including sensorineural hearing loss, seizures, chorea [6], and expressive language impairment [7]. A review of 300 patients with Kabuki syndrome stated that 87% demonstrate some cognitive impairment, 30% demonstrate hypotonia, 25% demonstrate microcephaly, and 8% demonstrate seizures [8]. As a result of organ failure (which is common), patients may require multiorgan transplants and chronic immunosuppressive medication. Although choreiform movements and bilateral dysmetria were evident in the upper extremities of a patient with Kabuki syndrome and anti-phospholipid antibodies [6], the physiologic tremor observed in our patient was not previously described, to the best of our knowledge. Magnetic resonance imaging hyperintensities in the dentate nuclei, lentiform nuclei, and red nuclei were also not previously reported in patients with Kabuki syndrome, to the best of our knowledge. These findings may represent an underlying abnormality present in a subset of patients presenting with Kabuki syndrome phenotype. Case Report The patient, a 27-year-old woman with Kabuki syndrome, presented to us with generalized seizures. Although the patient had manifested a febrile seizure at age 6 years, and had previously received phenytoin and phenobarbital for 3 years, she had, until recently, been seizure free with no need for antiepileptic medication. The breakthrough seizure occurred the day before her admission, and was witnessed by the family, who described convulsions, blank staring, and postictal confusion. Her appetite had decreased before her admission, and her parents reported that she had been more somnolent for the 2 days before her arrival at the hospital. No documentation existed of fever or chills, and she had just completed a course of ciprofloxacin for a urinary tract infection. The etiology of her breakthrough seizure was thought to be secondary to her hyponatremia (sodium concentration in the 120s mmol/L) and concurrent urinary tract infection. During her hospital course, a very fine, symmetric, physiologic tremor was evident in both upper extremities, although it did not hinder her in
From the *Department of Neurology, †Transplant Institute, and ‡ Department of Radiology, Georgetown University Hospital, Washington, DC; and §Department of Neurology, Kaiser Permanente, Suitland, Maryland.
Communications should be addressed to: Dr. Shamim; Department of Neurology, Kaiser Permanente; Mid-Atlantic Permanente Medical Group 5100; Suitland, MD 20746. E-mail: [email protected] Received October 14, 2009; accepted March 29, 2010.
148 PEDIATRIC NEUROLOGY Vol. 43 No. 2
Ó 2010 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2010.03.019 0887-8994/$—see front matter
any way. She had initially received levetiracetam for seizure management, which was subsequently changed to phenytoin because of her increased agitation and behavioral changes. Magnetic resonance imaging of the brain was performed to evaluate the etiology of her seizures, which revealed symmetric, T2-hyperintense lesions with mildly restricted diffusion in the lentiform nuclei, red nuclei, and dentate nuclei bilaterally (Fig 1). Subtle T2-hyperintensity was also evident in the corpus callosum. Electroencephalography did not reveal seizure discharges, and the hand tremor that was observed during the recording was not associated with any epileptiform discharges. She did not manifest further seizures during her hospital course. On physical examination, she exhibited characteristic features of Kabuki syndrome, including long palpebral fissures, arched eyebrows, and fetal fingertip pads (Fig 2). On neurologic examination, her Mini-Mental State Examination score was 28 out of 30. Her cranial nerves were intact. Her motor examination produced nonfocal results in both upper extremities, and she exhibited a fine, symmetric, physiologic tremor during sustained posturing. The tremor disappeared completely with movement. Her reflexes were symmetric. Her coordination was intact, with no evident dysmetria, intention tremor, or choreiform movements. A hematoma had developed in her right leg in 2007, and she had developed a foot drop in this leg after surgical correction, requiring the use of an ankle-foot orthosis. The remainder of her gait evaluation was unremarkable. She had been hospitalized in 2008 for intestinal pseudo-obstruction because of Kabuki syndrome, and subsequently required a liver transplant after developing liver failure because of parenteral nutrition. After her transplant, she also developed graft vs host disease, necessitating treatment with tacrolimus. Her serum tacrolimus levels were 3-7 ng/dL during our evaluation. Extensive evaluations with normal results involved serum copper, anti-cardiolipin antibodies, hepatitis B and C, Epstein-Barr virus, Lyme disease, selenium, liver function abnormalities, iron testing, ammonia, cerebral spinal fluid testing, lactate levels, and pyruvate levels. Cytomegalovirus polymerase chain reaction testing of her blood had produced positive results during a previous evaluation, but all subsequent testing and cytomegalovirus cultures produced negative results after treatment, including tests of her spinal fluid. Lupus anticoagulant testing produced positive results, and the antinuclear antibody testing produced positive results at a <1:40 titer. Her prothrombin time was mildly elevated to 14.8 seconds, and her partial thromboplastin time was normal. Her level of serum total carnitine was elevated, at 102 mmol/L (normal range, 31-67 mmol/L), and her free carnitine level was elevated, at 100 mmol/L (normal range, 25-55 mmol/L). A computed tomography scan of her head produced unremarkable results. A thrombophilia workup (involving protein C, protein S, factor II, homocysteine, factor V Leiden, and methyltetrahydrofolate reductase) produced negative results. Her serum phenytoin levels remained therapeutic during hospitalization.
Discussion We describe a patient with Kabuki syndrome who manifested multiple deep brain nuclei hyperintensities and physiologic tremor. Although involvement in the corpus callosum was previously reported [4], the pattern of nuclei involvement that we describe was not previously described. The constellation of our patient’s imaging findings suggests that the pathophysiology of Kabuki syndrome may preferentially affect the deep brain nuclei, and that several potential mechanisms could be contributory. The physiologic tremor was likely caused by multiple medications. One potential mechanism to explain the pattern of deep brain nuclei hyperintensities on magnetic resonance imaging may involve an autoimmune etiology. Multiple autoimmune abnormalities were reported in Kabuki syndrome, including hemolytic anemia, idiopathic thrombocytopenic purpura, thyroiditis, and vitiligo [9]. The presence of antiphospholipid antibodies in association with chorea in Kabuki syndrome was also reported by Gidwani et al. [6]. In the patient described by Gidwani et al. [6], multiple antiphospholipid antibodies were evident, including lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein. Microvascular thrombosis in the basal ganglia or direct immune action against the neuronal membranes may hypothetically contribute to the chorea. Our patient’s lupus anticoagulant test did produce positive results, suggesting that autoantibodies could be targeting the deep brain nuclei. However, our patient did not manifest chorea. Another mechanism to explain the pattern of deep brain nuclei hyperintensities may involve an underlying mitochondrial abnormality that preferentially affects the deep brain nuclei of patients with Kabuki syndrome. Growing evidence exists that mitochondrial degeneration could also preferentially affect the deep brain nuclei in Parkinson disease and Huntington disease. Although the tremor in these patients is not similar to that observed in our patient, the same general subcortical location may be shared between these disease processes. The pathogenesis of
Figure 1. Fluid-attenuated inversion recovery magnetic resonance images indicate hyperintensity within the bilateral red nuclei (left), dentate nuclei (middle), and lentiform nuclei (right).
Grunseich et al: Tremor and Hyperintensities in Kabuki Syndrome 149
should be undertaken, for a better determination of their prevalence and underlying etiology. Although the etiology of the Kabuki syndrome remains unclear, this entity may constitute a heterogeneous disease presenting with similar clinical phenotypes. Perhaps this heterogeneity constitutes part of the reason that a common genetic etiology has not been identified. A subset of patients with Kabuki syndrome may manifest mitochondrial abnormalities, as evidenced by our findings. A better understanding of this heterogeneous clinical syndrome requires more research. We thank the patient and her family for agreeing to the publication of the patient’s details and images. We refrain from using identifiable images of the patient, at the request of her family. Figure 2. Fetal fat pads, as previously described in patients with Kabuki syndrome. References
Parkinson disease may involve abnormal deep brain nuclei mitochondrial function, as indicated by defects in mitochondrial respiratory complex I function in patients with idiopathic Parkinson disease [10]. Evidence also exists that mitochondrial defects impair energy metabolism in Huntington disease, resulting in increased oxidative damage [11]. Our patient exhibited normal levels of lactate and pyruvate, which does not support the idea of a mitochondrial etiology. However, her total and free carnitine levels were elevated, which can occur in patients with carnitine palmitoyl transferase 1 deficiency. However, our patient does not present other laboratory evidence to suggest carnitine palmitoyl transferase deficiency, e.g., elevated liver function tests, hyperammonia, or hypoglycemia [12]. Although brain nuclei hyperintensities may have contributed to the patient’s tremor, tacrolimus could also account for the underlying etiology of her tremor. Tremor can develop in approximately 40% of patients on tacrolimus therapy, and may become severe to the extent that it affects handwriting [13]. Although the tremor may have occurred secondary to the tacrolimus, the magnetic resonance imaging findings are unlikely to be related to any neurotoxicity. The most common imaging feature from patients receiving tacrolimus comprises posterior leukoencephalopathy [14]. Case reports that documented imaging findings in association with tacrolimus usually reported subcortical white matter involvement and an onset of signs within 2 weeks of commencing tacrolimus [14,15]. Our patient demonstrated imaging findings in the deep brain nuclei, in contrast to the tacrolimus-associated findings. Because abnormalities of the central nervous system were reported in several patients with Kabuki syndrome, we recommend obtaining magnetic resonance imaging in any patient with Kabuki syndrome whose neurologic findings include tremor. The imaging findings that we report were not observed in other patients with Kabuki syndrome, and further investigation of these findings in this population
150 PEDIATRIC NEUROLOGY Vol. 43 No. 2
[1] Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: A syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-9. [2] Digilio MC, Marino B, Toscano A, Giannotti A, Dallapiccola B. Congenital heart defects in Kabuki syndrome. Am J Med Genet 2001; 100:269-74. [3] Ciprero LK, Clayton-Smith J, Donnai D, Zimmerman AR, Zachai HE, Ming EJ. Symptomatic Chiari I malformation in Kabuki syndrome. Am J Med Genet [A] 2005;132A:273-5. [4] Ben-Omran T, Teebi AS. Structural central nervous system (CNS) anomalies in Kabuki syndrome. Am J Med Genet [A] 2005; 137A:100-3. [5] Oksanen VE, Arvio MA, Peppo MM, Valanne LK, Sainio KO. Temporo-occipital spikes: A typical EEG finding in Kabuki syndrome. Pediatr Neurol 2004;30:67-70. [6] Gidwani P, Segal E, Shanske A, Driscoll C. Chorea associated with antiphospholipid antibodies in a patient with Kabuki syndrome. Am J Med Genet [A] 2007;143A:1338-41. [7] Defloor T, Borsel JV, Schrander-Stumpel CTRM, Curfs LMG. Expressive language in children with Kabuki syndrome. Am J Med Genet [A] 2005;132A:256-9. [8] Wessels MW, Brooks AS, Hoogeboom J, Niermeijer MF, Willems PJ. Kabuki syndrome: A review study of three hundred patients. Clin Dysmorphol 2002;11:95-102. [9] Ming JE, Russell KL, McDonal-McGinn DM, Zachai EH. Autoimmune disorders in Kabuki syndrome. Am J Med Genet [A] 2005; 132A:260-2. [10] Hattori N, Tanaka M, Ozawa T, Mizuno Y. Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson’s disease. Ann Neurol 1991;30:563-71. [11] Browne SE, Bowling AC, MacGarvey U, et al. Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997;41:646-53. [12] Longo N, Filippo CADS, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet [C] Semin Med Genet 2006;142C:77-85. [13] Wijdicks EF. Neurotoxicity of immunosuppressive drugs. Liver Transplant 2001;7:937-42. [14] Toroscik HV, Curless RG, Post J, Tzakis AG, Pearse L. FK506induced leukoencephalopathy in children with organ transplants. Neurology 1999;52:1497-500. [15] Oliverio PJ, Restrepo L, Mitchell SA, Tornatore CS, Frankel SR. Reversible tacrolimus-induced neurotoxicity isolated to the brain stem. AJNR 2000;21:1251-4.
Introduction Kabuki (makeup) syndrome was first described in a Japanese patient population by Niikawa et al. [1]. Patients with Kabuki syndrome manifest multiple congenital abnormalities, including characteristic facies with long palpebral fissures, eversion of the lower lateral eyelids, enlarged ears,
and depressed nasal tips. The cause remains unknown, and although several genetic loci were previously investigated, the causative genetic loci remain unidentified. In addition to the classic facial findings, patients with Kabuki syndrome also manifest characteristic skeletal abnormalities, short stature, abnormal dentition, and other visceral anomalies that may necessitate organ transplants [2]. Multiple abnormalities of the central nervous system were also reported, including Chiari I malformation [3], agenesis of the corpus callosum and atrophy of the hippocampus [4], and central hypoplasia [5]. Several clinical neurologic findings were also reported in patients with Kabuki syndrome, including sensorineural hearing loss, seizures, chorea [6], and expressive language impairment [7]. A review of 300 patients with Kabuki syndrome stated that 87% demonstrate some cognitive impairment, 30% demonstrate hypotonia, 25% demonstrate microcephaly, and 8% demonstrate seizures [8]. As a result of organ failure (which is common), patients may require multiorgan transplants and chronic immunosuppressive medication. Although choreiform movements and bilateral dysmetria were evident in the upper extremities of a patient with Kabuki syndrome and anti-phospholipid antibodies [6], the physiologic tremor observed in our patient was not previously described, to the best of our knowledge. Magnetic resonance imaging hyperintensities in the dentate nuclei, lentiform nuclei, and red nuclei were also not previously reported in patients with Kabuki syndrome, to the best of our knowledge. These findings may represent an underlying abnormality present in a subset of patients presenting with Kabuki syndrome phenotype. Case Report The patient, a 27-year-old woman with Kabuki syndrome, presented to us with generalized seizures. Although the patient had manifested a febrile seizure at age 6 years, and had previously received phenytoin and phenobarbital for 3 years, she had, until recently, been seizure free with no need for antiepileptic medication. The breakthrough seizure occurred the day before her admission, and was witnessed by the family, who described convulsions, blank staring, and postictal confusion. Her appetite had decreased before her admission, and her parents reported that she had been more somnolent for the 2 days before her arrival at the hospital. No documentation existed of fever or chills, and she had just completed a course of ciprofloxacin for a urinary tract infection. The etiology of her breakthrough seizure was thought to be secondary to her hyponatremia (sodium concentration in the 120s mmol/L) and concurrent urinary tract infection. During her hospital course, a very fine, symmetric, physiologic tremor was evident in both upper extremities, although it did not hinder her in
From the *Department of Neurology, †Transplant Institute, and ‡ Department of Radiology, Georgetown University Hospital, Washington, DC; and §Department of Neurology, Kaiser Permanente, Suitland, Maryland.
Communications should be addressed to: Dr. Shamim; Department of Neurology, Kaiser Permanente; Mid-Atlantic Permanente Medical Group 5100; Suitland, MD 20746. E-mail: [email protected] Received October 14, 2009; accepted March 29, 2010.
148 PEDIATRIC NEUROLOGY Vol. 43 No. 2
Ó 2010 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2010.03.019 0887-8994/$—see front matter
any way. She had initially received levetiracetam for seizure management, which was subsequently changed to phenytoin because of her increased agitation and behavioral changes. Magnetic resonance imaging of the brain was performed to evaluate the etiology of her seizures, which revealed symmetric, T2-hyperintense lesions with mildly restricted diffusion in the lentiform nuclei, red nuclei, and dentate nuclei bilaterally (Fig 1). Subtle T2-hyperintensity was also evident in the corpus callosum. Electroencephalography did not reveal seizure discharges, and the hand tremor that was observed during the recording was not associated with any epileptiform discharges. She did not manifest further seizures during her hospital course. On physical examination, she exhibited characteristic features of Kabuki syndrome, including long palpebral fissures, arched eyebrows, and fetal fingertip pads (Fig 2). On neurologic examination, her Mini-Mental State Examination score was 28 out of 30. Her cranial nerves were intact. Her motor examination produced nonfocal results in both upper extremities, and she exhibited a fine, symmetric, physiologic tremor during sustained posturing. The tremor disappeared completely with movement. Her reflexes were symmetric. Her coordination was intact, with no evident dysmetria, intention tremor, or choreiform movements. A hematoma had developed in her right leg in 2007, and she had developed a foot drop in this leg after surgical correction, requiring the use of an ankle-foot orthosis. The remainder of her gait evaluation was unremarkable. She had been hospitalized in 2008 for intestinal pseudo-obstruction because of Kabuki syndrome, and subsequently required a liver transplant after developing liver failure because of parenteral nutrition. After her transplant, she also developed graft vs host disease, necessitating treatment with tacrolimus. Her serum tacrolimus levels were 3-7 ng/dL during our evaluation. Extensive evaluations with normal results involved serum copper, anti-cardiolipin antibodies, hepatitis B and C, Epstein-Barr virus, Lyme disease, selenium, liver function abnormalities, iron testing, ammonia, cerebral spinal fluid testing, lactate levels, and pyruvate levels. Cytomegalovirus polymerase chain reaction testing of her blood had produced positive results during a previous evaluation, but all subsequent testing and cytomegalovirus cultures produced negative results after treatment, including tests of her spinal fluid. Lupus anticoagulant testing produced positive results, and the antinuclear antibody testing produced positive results at a <1:40 titer. Her prothrombin time was mildly elevated to 14.8 seconds, and her partial thromboplastin time was normal. Her level of serum total carnitine was elevated, at 102 mmol/L (normal range, 31-67 mmol/L), and her free carnitine level was elevated, at 100 mmol/L (normal range, 25-55 mmol/L). A computed tomography scan of her head produced unremarkable results. A thrombophilia workup (involving protein C, protein S, factor II, homocysteine, factor V Leiden, and methyltetrahydrofolate reductase) produced negative results. Her serum phenytoin levels remained therapeutic during hospitalization.
Discussion We describe a patient with Kabuki syndrome who manifested multiple deep brain nuclei hyperintensities and physiologic tremor. Although involvement in the corpus callosum was previously reported [4], the pattern of nuclei involvement that we describe was not previously described. The constellation of our patient’s imaging findings suggests that the pathophysiology of Kabuki syndrome may preferentially affect the deep brain nuclei, and that several potential mechanisms could be contributory. The physiologic tremor was likely caused by multiple medications. One potential mechanism to explain the pattern of deep brain nuclei hyperintensities on magnetic resonance imaging may involve an autoimmune etiology. Multiple autoimmune abnormalities were reported in Kabuki syndrome, including hemolytic anemia, idiopathic thrombocytopenic purpura, thyroiditis, and vitiligo [9]. The presence of antiphospholipid antibodies in association with chorea in Kabuki syndrome was also reported by Gidwani et al. [6]. In the patient described by Gidwani et al. [6], multiple antiphospholipid antibodies were evident, including lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein. Microvascular thrombosis in the basal ganglia or direct immune action against the neuronal membranes may hypothetically contribute to the chorea. Our patient’s lupus anticoagulant test did produce positive results, suggesting that autoantibodies could be targeting the deep brain nuclei. However, our patient did not manifest chorea. Another mechanism to explain the pattern of deep brain nuclei hyperintensities may involve an underlying mitochondrial abnormality that preferentially affects the deep brain nuclei of patients with Kabuki syndrome. Growing evidence exists that mitochondrial degeneration could also preferentially affect the deep brain nuclei in Parkinson disease and Huntington disease. Although the tremor in these patients is not similar to that observed in our patient, the same general subcortical location may be shared between these disease processes. The pathogenesis of
Figure 1. Fluid-attenuated inversion recovery magnetic resonance images indicate hyperintensity within the bilateral red nuclei (left), dentate nuclei (middle), and lentiform nuclei (right).
Grunseich et al: Tremor and Hyperintensities in Kabuki Syndrome 149
should be undertaken, for a better determination of their prevalence and underlying etiology. Although the etiology of the Kabuki syndrome remains unclear, this entity may constitute a heterogeneous disease presenting with similar clinical phenotypes. Perhaps this heterogeneity constitutes part of the reason that a common genetic etiology has not been identified. A subset of patients with Kabuki syndrome may manifest mitochondrial abnormalities, as evidenced by our findings. A better understanding of this heterogeneous clinical syndrome requires more research. We thank the patient and her family for agreeing to the publication of the patient’s details and images. We refrain from using identifiable images of the patient, at the request of her family. Figure 2. Fetal fat pads, as previously described in patients with Kabuki syndrome. References
Parkinson disease may involve abnormal deep brain nuclei mitochondrial function, as indicated by defects in mitochondrial respiratory complex I function in patients with idiopathic Parkinson disease [10]. Evidence also exists that mitochondrial defects impair energy metabolism in Huntington disease, resulting in increased oxidative damage [11]. Our patient exhibited normal levels of lactate and pyruvate, which does not support the idea of a mitochondrial etiology. However, her total and free carnitine levels were elevated, which can occur in patients with carnitine palmitoyl transferase 1 deficiency. However, our patient does not present other laboratory evidence to suggest carnitine palmitoyl transferase deficiency, e.g., elevated liver function tests, hyperammonia, or hypoglycemia [12]. Although brain nuclei hyperintensities may have contributed to the patient’s tremor, tacrolimus could also account for the underlying etiology of her tremor. Tremor can develop in approximately 40% of patients on tacrolimus therapy, and may become severe to the extent that it affects handwriting [13]. Although the tremor may have occurred secondary to the tacrolimus, the magnetic resonance imaging findings are unlikely to be related to any neurotoxicity. The most common imaging feature from patients receiving tacrolimus comprises posterior leukoencephalopathy [14]. Case reports that documented imaging findings in association with tacrolimus usually reported subcortical white matter involvement and an onset of signs within 2 weeks of commencing tacrolimus [14,15]. Our patient demonstrated imaging findings in the deep brain nuclei, in contrast to the tacrolimus-associated findings. Because abnormalities of the central nervous system were reported in several patients with Kabuki syndrome, we recommend obtaining magnetic resonance imaging in any patient with Kabuki syndrome whose neurologic findings include tremor. The imaging findings that we report were not observed in other patients with Kabuki syndrome, and further investigation of these findings in this population
150 PEDIATRIC NEUROLOGY Vol. 43 No. 2
[1] Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: A syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-9. [2] Digilio MC, Marino B, Toscano A, Giannotti A, Dallapiccola B. Congenital heart defects in Kabuki syndrome. Am J Med Genet 2001; 100:269-74. [3] Ciprero LK, Clayton-Smith J, Donnai D, Zimmerman AR, Zachai HE, Ming EJ. Symptomatic Chiari I malformation in Kabuki syndrome. Am J Med Genet [A] 2005;132A:273-5. [4] Ben-Omran T, Teebi AS. Structural central nervous system (CNS) anomalies in Kabuki syndrome. Am J Med Genet [A] 2005; 137A:100-3. [5] Oksanen VE, Arvio MA, Peppo MM, Valanne LK, Sainio KO. Temporo-occipital spikes: A typical EEG finding in Kabuki syndrome. Pediatr Neurol 2004;30:67-70. [6] Gidwani P, Segal E, Shanske A, Driscoll C. Chorea associated with antiphospholipid antibodies in a patient with Kabuki syndrome. Am J Med Genet [A] 2007;143A:1338-41. [7] Defloor T, Borsel JV, Schrander-Stumpel CTRM, Curfs LMG. Expressive language in children with Kabuki syndrome. Am J Med Genet [A] 2005;132A:256-9. [8] Wessels MW, Brooks AS, Hoogeboom J, Niermeijer MF, Willems PJ. Kabuki syndrome: A review study of three hundred patients. Clin Dysmorphol 2002;11:95-102. [9] Ming JE, Russell KL, McDonal-McGinn DM, Zachai EH. Autoimmune disorders in Kabuki syndrome. Am J Med Genet [A] 2005; 132A:260-2. [10] Hattori N, Tanaka M, Ozawa T, Mizuno Y. Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in Parkinson’s disease. Ann Neurol 1991;30:563-71. [11] Browne SE, Bowling AC, MacGarvey U, et al. Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997;41:646-53. [12] Longo N, Filippo CADS, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet [C] Semin Med Genet 2006;142C:77-85. [13] Wijdicks EF. Neurotoxicity of immunosuppressive drugs. Liver Transplant 2001;7:937-42. [14] Toroscik HV, Curless RG, Post J, Tzakis AG, Pearse L. FK506induced leukoencephalopathy in children with organ transplants. Neurology 1999;52:1497-500. [15] Oliverio PJ, Restrepo L, Mitchell SA, Tornatore CS, Frankel SR. Reversible tacrolimus-induced neurotoxicity isolated to the brain stem. AJNR 2000;21:1251-4.