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Quadrigeminal Cistern Arachnoid Cyst in a Patient With Kabuki Syndrome
Quadrigeminal Cistern Arachnoid Cyst in a Patient With Kabuki Syndrome Bülent Kara, MD*, Hülya Kayserili, MD†, Murat I˙mer, MD‡, Mine Çalıs¸kan, MD‡, and Meral Özmen, MD‡ Kabuki syndrome is a rare dysmorphic disorder characterized by peculiar facial appearance, developmental delay, skeletal abnormalities, mental retardation, and dermatoglyphic abnormalities. Neurologic anomalies are frequently observed. This report presents a 2-yearold male with Kabuki syndrome who had a quadrigeminal cistern arachnoid cyst: the second case of such an association to be reported in the literature. © 2006 by Elsevier Inc. All rights reserved. Kara B. Quadrigeminal cistern arachnoid cyst in a patient with kabuki syndrome. Pediatr Neurol 2006;34:478-480.
Introduction Kabuki syndrome is a multiple congenital anomaly/ mental retardation syndrome (OMIM 147920) characterized by craniofacial, dermatoglyphic, and skeletal abnormalities [1]. The characteristic facial features consist of long palpebral fissures with eversion of the lateral third of the lower eyelids, which are reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form [2]. It was first described in 1981 by Niikawa et al. [3]. More than 350 cases have been reported worldwide [1]. The etiology of Kabuki syndrome is undetermined [1]. Most cases are sporadic, but rare familial cases fitting autosomal dominant inheritance have been reported [4,5]. No bio-
From *Department of Pediatrics, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey; †Department of Genetics and ‡Division of Child Neurology, Istanbul University, Istanbul Medical Faculty, Çapa, Istanbul, Turkey.
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chemical or genetic marker is currently known for Kabuki syndrome, and the diagnosis is made purely on a clinical basis [5,6]. Neurologic anomalies are frequently reported for Kabuki syndrome. This study describes a patient with Kabuki syndrome with a quadrigeminal cistern arachnoid cyst identified on cranial magnetic resonance imaging.
Case Report A 13-month-old male was referred for developmental delay and recurrent urinary tract infections. He was born at term by normal spontaneous delivery after an uneventful pregnancy as the first child of healthy, nonconsanguineous parents. Maternal age was 25, paternal age was 24. Family history was unremarkable. Birth weight was 2700 gm; birth height and head circumference were not recorded. He had a history of respiratory distress for the first 4 postnatal days not necessitating mechanical ventilation, and temper tantrums in the first year of life. At 12 months of age, developmental delay was observed. At 2 years of age his weight was 9000 gm (below the third percentile; mean for 12 months), height was 77 cm (below the third percentile; mean for 14 months), and head circumference was 43.3 cm (below the third percentile; mean for 9 months). Physical examination revealed the following: blue sclerae, long palpebral fissures, laterally sparse eyebrows, depressed and wide nasal bridge, prominent ala nasi, prominent/anteriorly rotated and low-set ears, high palate, small and fan-shaped hands, brachydactyly, strabismus, persistent fetal finger pads, hemangioma on the neck, 3 ⫻ 4 cm hypopigmented lesion on right scapulae, 2 ⫻ 3 cm hyperpigmented lesion on left femur, simian crease on left, plantar edema, pes planus, nail dystrophy of toes, cryptorchidism, and micropenis (2.5 cm; below the 10th percentile) (Fig 1). Neurologic examination was normal except ataxic gait, visual loss, vomiting, headache, severe motor development, and language delay. Other system examinations were within normal limits. Abdominal ultrasonography revealed right ectopic pelvic kidney, and voiding cysto-urethrogram demonstrated grade 2 vesicoureteral reflux on the right. A small ventricular septal defect was detected on echocardiography. Metabolic screening, thyroid hormones, ophthalmologic examination, and hearing assessment were normal. Dysmorphic features were evaluated as Kabuki syndrome at
Communications should be addressed to: Dr. Kara; Ömerpas¸a Caddesi Güvenç Sokak Burç; Apartmanı No 17; Daire 3, 34730; Göztepe, Kadıköy; Istanbul, Turkey. E-mail: [email protected] Received July 6, 2005; accepted November 14, 2005.
© 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2005.11.006 ● 0887-8994/06/$—see front matter
Figure 1. Dysmorphic features of the patient with Kabuki syndrome; long palpebral fissures, laterally sparse eyebrows, depressed and wide nasal bridge, prominent ala nasi.
genetic consultation. Karyotype was 46,XY, with no chromosomal abnormalities. Cranial magnetic resonance imaging revealed a 4.8 ⫻ 7 ⫻ 7 cm arachnoidal cyst originated from the quadrigeminal cistern extending to the interhemispheric fissure. Cystoperitoneal shunt implantation was performed because of visual loss and the symptoms of increased intracranial pressure such as headache and vomiting (Fig 2). The patient manifested no symptoms after the operation, and his ventriculoperitoneal shunt is working efficiently. Discussion Niikawa et al. collected data from 62 patients with Kabuki syndrome from 33 institutions and described five cardinal manifestations: (1) a peculiar face in all cases, characterized by eversion of the lower lateral eyelid, arched eyebrows with sparse and dispersed lateral one third, depressed nasal tip, and prominent ears; (2) skeletal anomalies in 92% including brachydactyly V and spinal deformity with or without sagittal cleft vertebrae; (3) dermatoglyphic abnormalities in 93%, including increased
digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; (4) mild to moderate mental retardation in 92%; and (5) postnatal growth deficiency in 83% [7]. None of these cardinal manifestations except for the facies are absolutely necessary for diagnosis [6]. Typical dysmorphic features, brachydactyly, fingertip pads, growth, and mental retardation of the patient in this case report were compatible with the diagnosis of Kabuki syndrome. Central nervous system involvement is frequently reported in Kabuki syndrome [5]. Intellectual disability is the cardinal manifestation of the syndrome [5]. Other neurologic abnormalities include microcephaly, early hypotonia, feeding problems, cerebellar and brainstem atrophy, optic nerve atrophy, brachycephaly, VI nerve palsy, communication problems, and epilepsy [4,5,8,9]. Recent studies suggest that neurologic manifestations are probably more frequent in non-Asian patients [6]. Arachnoid cyst is rarely associated with Kabuki syndrome. Chu et al. first reported a 5-year-old Caucasian male with Kabuki syndrome who required surgery for a giant left temporoparietal arachnoid cyst at age 5½ years [10]. Our patient, who also had arachnoid cyst originating from the quadrigeminal cistern extending to the interhemispheric fissure, is the second patient with arachnoid cyst and Kabuki syndrome association in the literature. There could have been more cases reported with arachnoid cyst, if all the cases had been evaluated thoroughly for central nervous system malformations. In the clinical practice of neurology, central nervous system imaging is not a routine investigation when there is a definite diagnosis or no newly developing neurologic symptoms are present. The etiology of Kabuki syndrome appears to be genetic in etiology. However, little or no evidence of a genetic abnormality, neither chromosomal nor mendelian, can be established [2]. Most cases are sporadic. Autosomal dominant inheritance has been implicated in rare familial cases [5]. In a small number of patients, 13 various chromo-
Figure 2. Cranial computed tomography image illustrating the quadrigeminal cistern arachnoid cyst; 7 days (a) and 2 years (b) after cystoperitoneal shunt implantation.
Kara et al: Arachnoid Cyst and Kabuki Syndrome 479
somal abnormalities have been reported as a ring X or ring Y chromosome, inversion of Y chromosome, 45,X karyotype, unbalanced translocation of 6q and 12q, balanced translocation between 15q and 17q, inversion of 4p, pseudodicentric chromosome 13, and interstitial deletion of the short arm of chromosome 1 [6,8]. Milunsky and Huang revealed 8p22-8p23.1 duplication in six unrelated Kabuki syndrome patients with comparative genomic hybridization and bacterial artificial chromosome–fluorescent in situ hybridization [1]. Further reports did not support 8p22-8p23.1 duplication [11,12]. There was no other patient with Kabuki syndrome in the patient’s family, and 46,XY normal male karyotype was revealed at 550 band level. Epilepsy occurs in 16% to 39% of patients, and no specific epileptic syndrome has been reported [5,9]. Although no typical electroencephalographic finding was documented, temporo-occipital spikes in sleep electroencephalography in three Kabuki syndrome patients was reported by Oksanen et al. [5]. There was no history of seizure in the 2-year-old patient described in the present case study, and sleep electroencephalography was normal, but it is known that seizure may develop later in life in Kabuki syndrome. Neuroimaging often reveals mild enlargement of cerebral ventricles as a result of cerebral atrophy [6]. Cortical malformations, especially polymicrogyria, have been rarely described [6,9]. Cranial magnetic resonance imaging of the patient demonstrated normal findings except arachnoid cyst. Neurologic manifestations, such as mental retardation and epilepsy, are well-known characteristics of Kabuki syndrome. Although structural cerebral malformations are occasionally encountered, identification of these anomalies provides early and effective intervention for some of these anomalies and contributes to a better quality of life. Once the clinical diagnosis of Kabuki syndrome is established, further studies, electroencephalography and cranial
480
PEDIATRIC NEUROLOGY
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neuroimaging, should be performed as a part of follow-up assessment.
References [1] Milunsky JM, Huang XL. Unmasking Kabuki syndrome: Chromosome 8p22-8p23.1 duplication revealed by comparative genomic hybridization and BAC-FISH. Clin Genetic 2003;64:509. [2] Online Mendelian Inheritance in Man (OMIM): http:// www.ncbi.nlm.gov/OMIM/. Kabuki syndrome, MIM %147920. Center for Medical Genetics, Johns Hopkins University, Baltimore, MD, and the National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD. [3] Niikawa N, Matsuura N, Fukushima T, Ohsawa T, Kaljii T. Kabuki make-up syndrome: A syndrome with mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-9. [4] London Dysmorphology Database (version 1.0). 2003. Winter R, Baraitzer M, eds. London Medical Database. London: London Dysmorphology Database. [5] Oksanen VE, Arvio MA, Peippo MM, Valanne LK, Sainio KO. Temporo-occipital spikes: A typical EEG finding in Kabuki syndrome. Pediatr Neurol 2004;30:67-70. [6] Powell HWR, Hart PE, Sisodiya SM. Epilepsy and perisylvian polymicrogyria in a patient with Kabuki syndrome. Dev Med Child Neurol 2003;45:841-3. [7] Niikawa N, Kuroki Y, Kaljii T, et al. Kabuki make-up (NiikawaKuroki) syndrome: A study of 62 patients. Am J Med Genet 1988;31: 565-89. [8] Van Lierde KM, Borsel JV, von Caunwenberge P. Speech patterns in Kabuki make-up syndrome. J Commun Disord 2000;33:447– 62. [9] Gennaro GD, Condoluci C, Casali C, Ciccarelli O, Albertini G. Epilepsy and polymicrogyria in Kabuki make-up (Niikawa-Kuroki) syndrome. Pediatr Neurol 1999;566-8. [10] Chu DC, Finley SC, Young DW, Proud VK. CNS malformation in a child with Kabuki (Niikawa-Kuroki) syndrome. Am J Med Genet 1997;72:205-9. [11] Sanlaville D, Genevieve D, Bernardin C, et al. Failure to detect an 8p22-8p23.1 duplication in patients with Kabuki (Niikawa-Kuroki) syndrome. Eur J Hum Genet 2005;13:690-3. [12] Engelen JJ, Vaes-Peeters G, Schrander-Stumpel CT. Kabuki syndrome is not caused by an 8p duplication: A cytogenetic study in 20 patients. Am J Med Genet A 2005;132:276-7.
Introduction Kabuki syndrome is a multiple congenital anomaly/ mental retardation syndrome (OMIM 147920) characterized by craniofacial, dermatoglyphic, and skeletal abnormalities [1]. The characteristic facial features consist of long palpebral fissures with eversion of the lateral third of the lower eyelids, which are reminiscent of the make-up of actors of Kabuki, a Japanese traditional theatrical form [2]. It was first described in 1981 by Niikawa et al. [3]. More than 350 cases have been reported worldwide [1]. The etiology of Kabuki syndrome is undetermined [1]. Most cases are sporadic, but rare familial cases fitting autosomal dominant inheritance have been reported [4,5]. No bio-
From *Department of Pediatrics, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey; †Department of Genetics and ‡Division of Child Neurology, Istanbul University, Istanbul Medical Faculty, Çapa, Istanbul, Turkey.
478
PEDIATRIC NEUROLOGY
Vol. 34 No. 6
chemical or genetic marker is currently known for Kabuki syndrome, and the diagnosis is made purely on a clinical basis [5,6]. Neurologic anomalies are frequently reported for Kabuki syndrome. This study describes a patient with Kabuki syndrome with a quadrigeminal cistern arachnoid cyst identified on cranial magnetic resonance imaging.
Case Report A 13-month-old male was referred for developmental delay and recurrent urinary tract infections. He was born at term by normal spontaneous delivery after an uneventful pregnancy as the first child of healthy, nonconsanguineous parents. Maternal age was 25, paternal age was 24. Family history was unremarkable. Birth weight was 2700 gm; birth height and head circumference were not recorded. He had a history of respiratory distress for the first 4 postnatal days not necessitating mechanical ventilation, and temper tantrums in the first year of life. At 12 months of age, developmental delay was observed. At 2 years of age his weight was 9000 gm (below the third percentile; mean for 12 months), height was 77 cm (below the third percentile; mean for 14 months), and head circumference was 43.3 cm (below the third percentile; mean for 9 months). Physical examination revealed the following: blue sclerae, long palpebral fissures, laterally sparse eyebrows, depressed and wide nasal bridge, prominent ala nasi, prominent/anteriorly rotated and low-set ears, high palate, small and fan-shaped hands, brachydactyly, strabismus, persistent fetal finger pads, hemangioma on the neck, 3 ⫻ 4 cm hypopigmented lesion on right scapulae, 2 ⫻ 3 cm hyperpigmented lesion on left femur, simian crease on left, plantar edema, pes planus, nail dystrophy of toes, cryptorchidism, and micropenis (2.5 cm; below the 10th percentile) (Fig 1). Neurologic examination was normal except ataxic gait, visual loss, vomiting, headache, severe motor development, and language delay. Other system examinations were within normal limits. Abdominal ultrasonography revealed right ectopic pelvic kidney, and voiding cysto-urethrogram demonstrated grade 2 vesicoureteral reflux on the right. A small ventricular septal defect was detected on echocardiography. Metabolic screening, thyroid hormones, ophthalmologic examination, and hearing assessment were normal. Dysmorphic features were evaluated as Kabuki syndrome at
Communications should be addressed to: Dr. Kara; Ömerpas¸a Caddesi Güvenç Sokak Burç; Apartmanı No 17; Daire 3, 34730; Göztepe, Kadıköy; Istanbul, Turkey. E-mail: [email protected] Received July 6, 2005; accepted November 14, 2005.
© 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2005.11.006 ● 0887-8994/06/$—see front matter
Figure 1. Dysmorphic features of the patient with Kabuki syndrome; long palpebral fissures, laterally sparse eyebrows, depressed and wide nasal bridge, prominent ala nasi.
genetic consultation. Karyotype was 46,XY, with no chromosomal abnormalities. Cranial magnetic resonance imaging revealed a 4.8 ⫻ 7 ⫻ 7 cm arachnoidal cyst originated from the quadrigeminal cistern extending to the interhemispheric fissure. Cystoperitoneal shunt implantation was performed because of visual loss and the symptoms of increased intracranial pressure such as headache and vomiting (Fig 2). The patient manifested no symptoms after the operation, and his ventriculoperitoneal shunt is working efficiently. Discussion Niikawa et al. collected data from 62 patients with Kabuki syndrome from 33 institutions and described five cardinal manifestations: (1) a peculiar face in all cases, characterized by eversion of the lower lateral eyelid, arched eyebrows with sparse and dispersed lateral one third, depressed nasal tip, and prominent ears; (2) skeletal anomalies in 92% including brachydactyly V and spinal deformity with or without sagittal cleft vertebrae; (3) dermatoglyphic abnormalities in 93%, including increased
digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; (4) mild to moderate mental retardation in 92%; and (5) postnatal growth deficiency in 83% [7]. None of these cardinal manifestations except for the facies are absolutely necessary for diagnosis [6]. Typical dysmorphic features, brachydactyly, fingertip pads, growth, and mental retardation of the patient in this case report were compatible with the diagnosis of Kabuki syndrome. Central nervous system involvement is frequently reported in Kabuki syndrome [5]. Intellectual disability is the cardinal manifestation of the syndrome [5]. Other neurologic abnormalities include microcephaly, early hypotonia, feeding problems, cerebellar and brainstem atrophy, optic nerve atrophy, brachycephaly, VI nerve palsy, communication problems, and epilepsy [4,5,8,9]. Recent studies suggest that neurologic manifestations are probably more frequent in non-Asian patients [6]. Arachnoid cyst is rarely associated with Kabuki syndrome. Chu et al. first reported a 5-year-old Caucasian male with Kabuki syndrome who required surgery for a giant left temporoparietal arachnoid cyst at age 5½ years [10]. Our patient, who also had arachnoid cyst originating from the quadrigeminal cistern extending to the interhemispheric fissure, is the second patient with arachnoid cyst and Kabuki syndrome association in the literature. There could have been more cases reported with arachnoid cyst, if all the cases had been evaluated thoroughly for central nervous system malformations. In the clinical practice of neurology, central nervous system imaging is not a routine investigation when there is a definite diagnosis or no newly developing neurologic symptoms are present. The etiology of Kabuki syndrome appears to be genetic in etiology. However, little or no evidence of a genetic abnormality, neither chromosomal nor mendelian, can be established [2]. Most cases are sporadic. Autosomal dominant inheritance has been implicated in rare familial cases [5]. In a small number of patients, 13 various chromo-
Figure 2. Cranial computed tomography image illustrating the quadrigeminal cistern arachnoid cyst; 7 days (a) and 2 years (b) after cystoperitoneal shunt implantation.
Kara et al: Arachnoid Cyst and Kabuki Syndrome 479
somal abnormalities have been reported as a ring X or ring Y chromosome, inversion of Y chromosome, 45,X karyotype, unbalanced translocation of 6q and 12q, balanced translocation between 15q and 17q, inversion of 4p, pseudodicentric chromosome 13, and interstitial deletion of the short arm of chromosome 1 [6,8]. Milunsky and Huang revealed 8p22-8p23.1 duplication in six unrelated Kabuki syndrome patients with comparative genomic hybridization and bacterial artificial chromosome–fluorescent in situ hybridization [1]. Further reports did not support 8p22-8p23.1 duplication [11,12]. There was no other patient with Kabuki syndrome in the patient’s family, and 46,XY normal male karyotype was revealed at 550 band level. Epilepsy occurs in 16% to 39% of patients, and no specific epileptic syndrome has been reported [5,9]. Although no typical electroencephalographic finding was documented, temporo-occipital spikes in sleep electroencephalography in three Kabuki syndrome patients was reported by Oksanen et al. [5]. There was no history of seizure in the 2-year-old patient described in the present case study, and sleep electroencephalography was normal, but it is known that seizure may develop later in life in Kabuki syndrome. Neuroimaging often reveals mild enlargement of cerebral ventricles as a result of cerebral atrophy [6]. Cortical malformations, especially polymicrogyria, have been rarely described [6,9]. Cranial magnetic resonance imaging of the patient demonstrated normal findings except arachnoid cyst. Neurologic manifestations, such as mental retardation and epilepsy, are well-known characteristics of Kabuki syndrome. Although structural cerebral malformations are occasionally encountered, identification of these anomalies provides early and effective intervention for some of these anomalies and contributes to a better quality of life. Once the clinical diagnosis of Kabuki syndrome is established, further studies, electroencephalography and cranial
480
PEDIATRIC NEUROLOGY
Vol. 34 No. 6
neuroimaging, should be performed as a part of follow-up assessment.
References [1] Milunsky JM, Huang XL. Unmasking Kabuki syndrome: Chromosome 8p22-8p23.1 duplication revealed by comparative genomic hybridization and BAC-FISH. Clin Genetic 2003;64:509. [2] Online Mendelian Inheritance in Man (OMIM): http:// www.ncbi.nlm.gov/OMIM/. Kabuki syndrome, MIM %147920. Center for Medical Genetics, Johns Hopkins University, Baltimore, MD, and the National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD. [3] Niikawa N, Matsuura N, Fukushima T, Ohsawa T, Kaljii T. Kabuki make-up syndrome: A syndrome with mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-9. [4] London Dysmorphology Database (version 1.0). 2003. Winter R, Baraitzer M, eds. London Medical Database. London: London Dysmorphology Database. [5] Oksanen VE, Arvio MA, Peippo MM, Valanne LK, Sainio KO. Temporo-occipital spikes: A typical EEG finding in Kabuki syndrome. Pediatr Neurol 2004;30:67-70. [6] Powell HWR, Hart PE, Sisodiya SM. Epilepsy and perisylvian polymicrogyria in a patient with Kabuki syndrome. Dev Med Child Neurol 2003;45:841-3. [7] Niikawa N, Kuroki Y, Kaljii T, et al. Kabuki make-up (NiikawaKuroki) syndrome: A study of 62 patients. Am J Med Genet 1988;31: 565-89. [8] Van Lierde KM, Borsel JV, von Caunwenberge P. Speech patterns in Kabuki make-up syndrome. J Commun Disord 2000;33:447– 62. [9] Gennaro GD, Condoluci C, Casali C, Ciccarelli O, Albertini G. Epilepsy and polymicrogyria in Kabuki make-up (Niikawa-Kuroki) syndrome. Pediatr Neurol 1999;566-8. [10] Chu DC, Finley SC, Young DW, Proud VK. CNS malformation in a child with Kabuki (Niikawa-Kuroki) syndrome. Am J Med Genet 1997;72:205-9. [11] Sanlaville D, Genevieve D, Bernardin C, et al. Failure to detect an 8p22-8p23.1 duplication in patients with Kabuki (Niikawa-Kuroki) syndrome. Eur J Hum Genet 2005;13:690-3. [12] Engelen JJ, Vaes-Peeters G, Schrander-Stumpel CT. Kabuki syndrome is not caused by an 8p duplication: A cytogenetic study in 20 patients. Am J Med Genet A 2005;132:276-7.