- Email: [email protected]
MPPH Syndrome: Two New Cases
Case Reports
MPPH Syndrome: Two New Cases Wendy L. Osterling, MD*†, Richard S. Boyer, MD‡, Gary L. Hedlund, DO‡, and James F. Bale, Jr., MD*† This report describes 2 additional cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, a recently recognized disorder of infants and young children with macrocrania, developmental delay/mental retardation, and often epilepsy. Medulloblastoma, a previously unreported feature in megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, developed in one child at 3 years of age. Although the disorder is presumed to be genetic, the cause of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome has not yet been determined. Ó 2011 Elsevier Inc. All rights reserved. Osterling WL, Boyer RS, Hedlund GL, Bale JF, Jr. MPPH syndrome: two new cases. Pediatr Neurol 2011;44: 370-373.
Introduction Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH) syndrome was first reported in 2004 [1]. Since the initial description of 5 unrelated children with the disorder, a small number of other cases has been reported [2-7]. The prominent features consist of megalencephaly, perisylvian polymicrogyria, hydrocephalus, and polydactyly, although there are variations in the extent of these features [6]. Children with megalencephaly and perisylvian polymicrogyria with post-
axial polydactyly and hydrocephalus syndrome often have cortical visual impairment, developmental delay/mental retardation, and epilepsy. Although the precise cause of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome has not been determined, the disorder is presumed genetic. Some authors have recently suggested that this disorder may overlap with macrocephaly-capillary malformation syndrome [6]. In this report, we describe 2 additional children with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome. The first child had a Chiari 1 malformation, a feature shared with macrocephaly-capillary malformation syndrome. Medulloblastoma, a previously unreported association with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, occurred in the second child.
Case Reports Case 1 An infant girl was evaluated because of a head circumference of 42.5 cm (>98th percentile) at birth. Ultrasound of the head suggested mildly enlarged ventricles. Brain magnetic resonance imaging (MRI) at 2 weeks of age confirmed ventriculomegaly and demonstrated extensive cortical dysplasia consisting of polymicrogyria of the frontal, parietal, temporal, and opercular regions bilaterally (Fig 1a-c). Chiari 1 malformation was also present (Fig 1b). Examination revealed frontal bossing and diffuse hypotonia. At 6 months of age, a ventriculoatrial shunt was placed because of progressive ventriculomegaly. At 7 months of age, she had recurring episodes of unprovoked emesis and vertical eye deviation suggesting seizures. An electroencephalogram (EEG) was abnormal, revealing diffuse 3-4 Hz activity and frequent sharp and slow wave discharges from the right hemisphere, especially in sleep. With phenobarbital therapy, the episodes of emesis and eye deviation resolved. However, at 11 months of age, infantile spasms appeared, and an EEG now demonstrated hypsarrhythmia. She was treated with adrenocorticotrophic hormone, 150 units/m2 daily for 2 weeks, and with remission of her infantile spasms, adrenocorticotrophic hormone was gradually withdrawn and discontinued over the subsequent 4 weeks. Her EEG returned to the baseline features, and although the infantile spasms ceased, she continued to have occasional events consisting of brief shoulder movements and eye closure. At 4 years of age, levetiracetam was substituted for phenobarbital. Other than a complex partial seizure, consisting of staring and unresponsiveness after a measles-mumps-rubella immunization at 6 years of age, her seizures remained well controlled.
From the Departments of *Pediatrics, †Neurology, and ‡Radiology, the University of Utah School of Medicine, Salt Lake City, Utah, and Primary Children’s Medical Center, Intermountain Healthcare Inc., Salt Lake City, Utah.
Communication should be addressed to: Dr. Bale; Third Floor; Primary Children’s Medical Center; 100 N Mario Capecchi Drive; Salt Lake City, UT 84113. E-mail: [email protected] Received August 3, 2010; accepted December 7, 2010.
370 PEDIATRIC NEUROLOGY Vol. 44 No. 5
Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2010.12.009 0887-8994/$ - see front matter
Figure 1. Case 1. (A) Axial T2 magnetic resonance imaging (MRI) reveals moderate ventriculomegaly, cavum septum pellucidum, and extensive frontal and parietal cortical thickening compatible with dysplasia. (B) Sagittal T1 MRI reveals upward bowing of the third ventricle, thinning of the corpus callosum, and downward displacement of the cerebellar tonsils compatible with a Chiari 1 malformation. (C) Parasagittal T1 MRI reveals extensive polymicrogyria.
When last assessed at 7 years of age, her general examination was normal except for macrocephaly (occipital-frontal circumference >98th percentile), a gastrostomy feeding tube, and global developmental delay. Neurologic examination revealed bilateral horizontal nystagmus, pseudobulbar palsy, diffuse hypotonia, normal strength, mildly hypoactive (1+) muscle stretch reflexes, and a wide-based gait when she walked with a walker. She cruised independently along furniture, said ‘‘mama’’ nonspecifically, used a fine pincer grasp, and indicated her wants by gestures or behaviors.
Case 2 A 3-month-old boy, the first child of healthy, unrelated parents, was evaluated for macrocephaly. Macrocrania had been identified in utero, but the ventricles were normal in size on the prenatal ultrasound examinations. Computed tomography of the head at 4 weeks of age revealed moderate lateral and third ventricular dilation, prominent extra-axial subarachnoid spaces, and features suggesting cortical dysplasia. Brain MRI at 2 months of age demonstrated moderate ventriculomegaly and extensive bilateral perisylvian cortical dysplasia involving the frontal, parietal, and temporal lobes (Fig 2a,b). Examination at 3 months revealed mildly dysmorphic facial features, large anterior fontanel (at least 5 5 cm), and a head circumference of 44.7 cm (>98th percentile). An extra digit had been amputated at birth from the base of the little finger of one hand. At 2 years of age, he was developmentally delayed with diffuse hypotonia. His motor and verbal development was at the 6-month level. He had a single, brief seizure after varicella vaccination. Because of unexplained episodes of emesis and unresponsiveness at 3 years of age, he underwent an EEG and a repeat brain MRI. The EEG was abnormal, with a multifocal seizure tendency, as well as diffuse and focal cerebral dysfunction. The brain MRI at this time revealed a medulloblastoma (Fig 2c) that subsequently responded well to surgical resection, radiation therapy (total of 2,340 cGy to the neural axis and 5,400 cGy to the posterior fossa), and chemotherapy (ACNS0331 protocol consisting of cycles of vincristine and cyclophosphamide). A spine MRI revealed no metastases. When last assessed at 5 years of age, he remained in remission and had occasional clusters of myoclonic seizures lasting 5 to 6 minutes, which his parents preferred not to treat. Neurologic examination revealed macrocephaly (occipital-frontal circumference >98th percentile), inconsistent visual fixation and pursuit, pseudobulbar palsy, diffuse hypotonia, absent muscle stretch reflexes (secondary to vincristine therapy), and global developmental delay. He was unable to assume a sitting position or stand alone, and he spoke no recognizable words.
Diagnostic Evaluation Both children had normal high-resolution karyotypes without visible duplications or deletions. Comparative genomic hybridization studies were not obtained as a result of lack of insurance support. In both cases, neuroimaging studies revealed cortical dysplasia and extensive polymicrogyria (Figs 1a,c and 2a). Both children had lateral and third ventricular dilation (Figs 1a and 2a), although the degree of ventriculomegaly was modest in the second child and did not require shunt placement. In both cases, the aqueducts of Sylvius and fourth ventricles were small (Figs 1b and 2b), compatible with relative aqueductal obstruction. The myelination patterns were normal in each child. In case 2, the second MRI (Fig 2c) revealed a fourth ventricular tumor that was pathologically confirmed to be a medulloblastoma.
Discussion The children’s features of megalencephaly, polymicrogyria, polydactyly (case 2), and hydrocephalus conform to the clinical definition and descriptions of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome [1]. To date, all reported cases of this syndrome, including both of the children in this report, have had perisylvian polymicrogyria. All but 2 have had hydrocephalus [1-4,7], and at least 6 children, including one described here, have required shunt placements to treat the hydrocephalus. Aqueductal obstruction appears to contribute to hydrocephalus in this syndrome because the fourth ventricle has been normal or small in most cases [1], a feature illustrated in Figures 1b and 2b. Most children, including one in this report, have had postaxial polydactyly. Polymicrogyria occurs in several brain overgrowth syndromes, including Sotos, Weaver, Beckwith-Wiedemann, Simpson-Golabi-Behmel, and macrocephaly-capillary malformation syndromes [8]. Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes are caused by mutations in the 11p15.5 chromosome, whereas Sotos and Weaver syndromes result from microdeletions in the NSD1 gene on chromosome 5. To date, mutations in
Osterling et al: MPPH Syndrome 371
Figure 2. Case 2. (A) Axial T2 magnetic resonance imaging (MRI) at 2 months of age reveals mild ventriculomegaly and extensive frontal and parietal cortical dysplasia compatible with polymicrogyria. (B) Sagittal T2 MRI at 2 months of age reveals thinning of the corpus callosum and a normal cerebellum and fourth ventricle. (C) Axial fluid-attenuated inversion-recovery MRI with intravenous gadolinium contrast at 3 years of age reveals a posterior fossa/ fourth ventricular tumor proven to be a medulloblastoma.
11p15.5 or NSD1 have not been identified in children with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome. Other bilateral polymicrogyria syndromes have been recognized, including central macrogyria, parasagittal parieto-occipital polymicrogyria and epilepsy, frontal polymicrogyria, perisylvian polymicrogyria, and generalized polymicrogyria [8]. Disorders with macrocephaly and polydactyly include Simpson-Golabi-Behmel, Greig, and macrocephalycapillary malformation syndromes. Gripp et al. recently reported that macrocephalycapillary malformation syndrome shares several features with the megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome and suggested that these 2 disorders may represent a spectrum of the same genetic disorder [6]. Crowding of the posterior fossa and Chiari malformation, features of macrocephaly-capillary malformation syndrome [9], were present in patient 1, but she lacked facial capillary malformations or skeletal asymmetries, features commonly observed in children with macrocephaly-capillary malformation syndrome. Identification of a specific genetic abnormality in children with either megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome or macrocephaly-capillary malformation syndrome will eventually enable investigators to determine whether these syndromes are manifestations of the same genetic disorder. Case 2 differs from all prior cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome in the occurrence of a posterior fossa tumor. Although this may represent a random event, the observation suggests that clinicians should remain alert for the possibility of posterior fossa or other central nervous system tumors in children with either
372 PEDIATRIC NEUROLOGY Vol. 44 No. 5
megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome or macrocephaly-capillary malformation syndrome. Central nervous system tumors resembling meningiomas have been observed in at least 2 children with macrocephalycapillary malformation syndrome [9], indicating that central nervous system tumors may be additional clinical manifestations of these rare syndromes. The authors thank the parents of both children for their reading of the article. The cases were presented as a poster at the 133rd Annual Meeting of the American Neurological Association, Salt Lake City, UT, October 2008, and published as an abstract for this meeting (Osterling WL, Boyer R, Hedlund G, Bale JF. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH) syndrome: Two new cases and literature review. Ann Neurol 2008;64:S63).
References [1] Mirzaa G, Dodge NN, Glass I, et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: A rare brain malformation syndrome associated with mental retardation and seizures. Neuropediatrics 2004;35:353-9. [2] Colombani M, Chouchane M, Pitelet G, et al. A new case of megalencephaly and perisylvian polymicrogyria with post-axial polydactyly and hydrocephalus. Eur J Med Genet 2006;49:466-71. [3] Tohyama J, Akasaka N, Saito N, Yoshimura J, Nishiyama K, Kato M. Megalencephaly and polymicrogyria with polydactyly syndrome. Pediat Neurol 2007;37:148-51. [4] Garavelli L, Gaureschi E, Errico S, et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): Report of a new case. Neuropediatrics 2007; 38:200-3. [5] Pisano T, Meloni M, Cianchetti C, Falchi M, Nucaro A, Pruna D. Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome: A new case with syndactyly. J Child Neurol 2008;23:916-8. [6] Gripp KW, Hopkins E, Vinkler C, et al. Significant overlap and possible identity of macrocephaly capillary malformation and
megalencephaly, polymicrogyria-polydactyly hydrocephalus syndromes. Am J Med Genet 2009;149A:868-76. [7] Tore HG, McKinney AM, Nagar VA, Lohman B, Truwit CL, Raybaud C. Syndrome of megalencephaly, polydactyly, and polymicrogyria lacking frank hydrocephalus, with associated MR imaging findings. AJNR Am J Neuroradiol 2009;30:1620-2.
[8] Barkovich AJ. Malformations secondary to abnormal cortical organization. Polymicrogyria. In: Barkovich AJ. Pediatric neuroimaging. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2000:311-7. [9] Conway RL, Pressman BD, Dobyns WB, et al. Neuroimaging features in macrocephaly-capillary malformation syndrome, a longitudinal study of 17 patients. Am J Med Genet A 2007;143A:2981-3008.
Osterling et al: MPPH Syndrome 373
MPPH Syndrome: Two New Cases Wendy L. Osterling, MD*†, Richard S. Boyer, MD‡, Gary L. Hedlund, DO‡, and James F. Bale, Jr., MD*† This report describes 2 additional cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, a recently recognized disorder of infants and young children with macrocrania, developmental delay/mental retardation, and often epilepsy. Medulloblastoma, a previously unreported feature in megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, developed in one child at 3 years of age. Although the disorder is presumed to be genetic, the cause of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome has not yet been determined. Ó 2011 Elsevier Inc. All rights reserved. Osterling WL, Boyer RS, Hedlund GL, Bale JF, Jr. MPPH syndrome: two new cases. Pediatr Neurol 2011;44: 370-373.
Introduction Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH) syndrome was first reported in 2004 [1]. Since the initial description of 5 unrelated children with the disorder, a small number of other cases has been reported [2-7]. The prominent features consist of megalencephaly, perisylvian polymicrogyria, hydrocephalus, and polydactyly, although there are variations in the extent of these features [6]. Children with megalencephaly and perisylvian polymicrogyria with post-
axial polydactyly and hydrocephalus syndrome often have cortical visual impairment, developmental delay/mental retardation, and epilepsy. Although the precise cause of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome has not been determined, the disorder is presumed genetic. Some authors have recently suggested that this disorder may overlap with macrocephaly-capillary malformation syndrome [6]. In this report, we describe 2 additional children with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome. The first child had a Chiari 1 malformation, a feature shared with macrocephaly-capillary malformation syndrome. Medulloblastoma, a previously unreported association with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome, occurred in the second child.
Case Reports Case 1 An infant girl was evaluated because of a head circumference of 42.5 cm (>98th percentile) at birth. Ultrasound of the head suggested mildly enlarged ventricles. Brain magnetic resonance imaging (MRI) at 2 weeks of age confirmed ventriculomegaly and demonstrated extensive cortical dysplasia consisting of polymicrogyria of the frontal, parietal, temporal, and opercular regions bilaterally (Fig 1a-c). Chiari 1 malformation was also present (Fig 1b). Examination revealed frontal bossing and diffuse hypotonia. At 6 months of age, a ventriculoatrial shunt was placed because of progressive ventriculomegaly. At 7 months of age, she had recurring episodes of unprovoked emesis and vertical eye deviation suggesting seizures. An electroencephalogram (EEG) was abnormal, revealing diffuse 3-4 Hz activity and frequent sharp and slow wave discharges from the right hemisphere, especially in sleep. With phenobarbital therapy, the episodes of emesis and eye deviation resolved. However, at 11 months of age, infantile spasms appeared, and an EEG now demonstrated hypsarrhythmia. She was treated with adrenocorticotrophic hormone, 150 units/m2 daily for 2 weeks, and with remission of her infantile spasms, adrenocorticotrophic hormone was gradually withdrawn and discontinued over the subsequent 4 weeks. Her EEG returned to the baseline features, and although the infantile spasms ceased, she continued to have occasional events consisting of brief shoulder movements and eye closure. At 4 years of age, levetiracetam was substituted for phenobarbital. Other than a complex partial seizure, consisting of staring and unresponsiveness after a measles-mumps-rubella immunization at 6 years of age, her seizures remained well controlled.
From the Departments of *Pediatrics, †Neurology, and ‡Radiology, the University of Utah School of Medicine, Salt Lake City, Utah, and Primary Children’s Medical Center, Intermountain Healthcare Inc., Salt Lake City, Utah.
Communication should be addressed to: Dr. Bale; Third Floor; Primary Children’s Medical Center; 100 N Mario Capecchi Drive; Salt Lake City, UT 84113. E-mail: [email protected] Received August 3, 2010; accepted December 7, 2010.
370 PEDIATRIC NEUROLOGY Vol. 44 No. 5
Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2010.12.009 0887-8994/$ - see front matter
Figure 1. Case 1. (A) Axial T2 magnetic resonance imaging (MRI) reveals moderate ventriculomegaly, cavum septum pellucidum, and extensive frontal and parietal cortical thickening compatible with dysplasia. (B) Sagittal T1 MRI reveals upward bowing of the third ventricle, thinning of the corpus callosum, and downward displacement of the cerebellar tonsils compatible with a Chiari 1 malformation. (C) Parasagittal T1 MRI reveals extensive polymicrogyria.
When last assessed at 7 years of age, her general examination was normal except for macrocephaly (occipital-frontal circumference >98th percentile), a gastrostomy feeding tube, and global developmental delay. Neurologic examination revealed bilateral horizontal nystagmus, pseudobulbar palsy, diffuse hypotonia, normal strength, mildly hypoactive (1+) muscle stretch reflexes, and a wide-based gait when she walked with a walker. She cruised independently along furniture, said ‘‘mama’’ nonspecifically, used a fine pincer grasp, and indicated her wants by gestures or behaviors.
Case 2 A 3-month-old boy, the first child of healthy, unrelated parents, was evaluated for macrocephaly. Macrocrania had been identified in utero, but the ventricles were normal in size on the prenatal ultrasound examinations. Computed tomography of the head at 4 weeks of age revealed moderate lateral and third ventricular dilation, prominent extra-axial subarachnoid spaces, and features suggesting cortical dysplasia. Brain MRI at 2 months of age demonstrated moderate ventriculomegaly and extensive bilateral perisylvian cortical dysplasia involving the frontal, parietal, and temporal lobes (Fig 2a,b). Examination at 3 months revealed mildly dysmorphic facial features, large anterior fontanel (at least 5 5 cm), and a head circumference of 44.7 cm (>98th percentile). An extra digit had been amputated at birth from the base of the little finger of one hand. At 2 years of age, he was developmentally delayed with diffuse hypotonia. His motor and verbal development was at the 6-month level. He had a single, brief seizure after varicella vaccination. Because of unexplained episodes of emesis and unresponsiveness at 3 years of age, he underwent an EEG and a repeat brain MRI. The EEG was abnormal, with a multifocal seizure tendency, as well as diffuse and focal cerebral dysfunction. The brain MRI at this time revealed a medulloblastoma (Fig 2c) that subsequently responded well to surgical resection, radiation therapy (total of 2,340 cGy to the neural axis and 5,400 cGy to the posterior fossa), and chemotherapy (ACNS0331 protocol consisting of cycles of vincristine and cyclophosphamide). A spine MRI revealed no metastases. When last assessed at 5 years of age, he remained in remission and had occasional clusters of myoclonic seizures lasting 5 to 6 minutes, which his parents preferred not to treat. Neurologic examination revealed macrocephaly (occipital-frontal circumference >98th percentile), inconsistent visual fixation and pursuit, pseudobulbar palsy, diffuse hypotonia, absent muscle stretch reflexes (secondary to vincristine therapy), and global developmental delay. He was unable to assume a sitting position or stand alone, and he spoke no recognizable words.
Diagnostic Evaluation Both children had normal high-resolution karyotypes without visible duplications or deletions. Comparative genomic hybridization studies were not obtained as a result of lack of insurance support. In both cases, neuroimaging studies revealed cortical dysplasia and extensive polymicrogyria (Figs 1a,c and 2a). Both children had lateral and third ventricular dilation (Figs 1a and 2a), although the degree of ventriculomegaly was modest in the second child and did not require shunt placement. In both cases, the aqueducts of Sylvius and fourth ventricles were small (Figs 1b and 2b), compatible with relative aqueductal obstruction. The myelination patterns were normal in each child. In case 2, the second MRI (Fig 2c) revealed a fourth ventricular tumor that was pathologically confirmed to be a medulloblastoma.
Discussion The children’s features of megalencephaly, polymicrogyria, polydactyly (case 2), and hydrocephalus conform to the clinical definition and descriptions of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome [1]. To date, all reported cases of this syndrome, including both of the children in this report, have had perisylvian polymicrogyria. All but 2 have had hydrocephalus [1-4,7], and at least 6 children, including one described here, have required shunt placements to treat the hydrocephalus. Aqueductal obstruction appears to contribute to hydrocephalus in this syndrome because the fourth ventricle has been normal or small in most cases [1], a feature illustrated in Figures 1b and 2b. Most children, including one in this report, have had postaxial polydactyly. Polymicrogyria occurs in several brain overgrowth syndromes, including Sotos, Weaver, Beckwith-Wiedemann, Simpson-Golabi-Behmel, and macrocephaly-capillary malformation syndromes [8]. Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes are caused by mutations in the 11p15.5 chromosome, whereas Sotos and Weaver syndromes result from microdeletions in the NSD1 gene on chromosome 5. To date, mutations in
Osterling et al: MPPH Syndrome 371
Figure 2. Case 2. (A) Axial T2 magnetic resonance imaging (MRI) at 2 months of age reveals mild ventriculomegaly and extensive frontal and parietal cortical dysplasia compatible with polymicrogyria. (B) Sagittal T2 MRI at 2 months of age reveals thinning of the corpus callosum and a normal cerebellum and fourth ventricle. (C) Axial fluid-attenuated inversion-recovery MRI with intravenous gadolinium contrast at 3 years of age reveals a posterior fossa/ fourth ventricular tumor proven to be a medulloblastoma.
11p15.5 or NSD1 have not been identified in children with megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome. Other bilateral polymicrogyria syndromes have been recognized, including central macrogyria, parasagittal parieto-occipital polymicrogyria and epilepsy, frontal polymicrogyria, perisylvian polymicrogyria, and generalized polymicrogyria [8]. Disorders with macrocephaly and polydactyly include Simpson-Golabi-Behmel, Greig, and macrocephalycapillary malformation syndromes. Gripp et al. recently reported that macrocephalycapillary malformation syndrome shares several features with the megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome and suggested that these 2 disorders may represent a spectrum of the same genetic disorder [6]. Crowding of the posterior fossa and Chiari malformation, features of macrocephaly-capillary malformation syndrome [9], were present in patient 1, but she lacked facial capillary malformations or skeletal asymmetries, features commonly observed in children with macrocephaly-capillary malformation syndrome. Identification of a specific genetic abnormality in children with either megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome or macrocephaly-capillary malformation syndrome will eventually enable investigators to determine whether these syndromes are manifestations of the same genetic disorder. Case 2 differs from all prior cases of megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome in the occurrence of a posterior fossa tumor. Although this may represent a random event, the observation suggests that clinicians should remain alert for the possibility of posterior fossa or other central nervous system tumors in children with either
372 PEDIATRIC NEUROLOGY Vol. 44 No. 5
megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus syndrome or macrocephaly-capillary malformation syndrome. Central nervous system tumors resembling meningiomas have been observed in at least 2 children with macrocephalycapillary malformation syndrome [9], indicating that central nervous system tumors may be additional clinical manifestations of these rare syndromes. The authors thank the parents of both children for their reading of the article. The cases were presented as a poster at the 133rd Annual Meeting of the American Neurological Association, Salt Lake City, UT, October 2008, and published as an abstract for this meeting (Osterling WL, Boyer R, Hedlund G, Bale JF. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH) syndrome: Two new cases and literature review. Ann Neurol 2008;64:S63).
References [1] Mirzaa G, Dodge NN, Glass I, et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: A rare brain malformation syndrome associated with mental retardation and seizures. Neuropediatrics 2004;35:353-9. [2] Colombani M, Chouchane M, Pitelet G, et al. A new case of megalencephaly and perisylvian polymicrogyria with post-axial polydactyly and hydrocephalus. Eur J Med Genet 2006;49:466-71. [3] Tohyama J, Akasaka N, Saito N, Yoshimura J, Nishiyama K, Kato M. Megalencephaly and polymicrogyria with polydactyly syndrome. Pediat Neurol 2007;37:148-51. [4] Garavelli L, Gaureschi E, Errico S, et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): Report of a new case. Neuropediatrics 2007; 38:200-3. [5] Pisano T, Meloni M, Cianchetti C, Falchi M, Nucaro A, Pruna D. Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome: A new case with syndactyly. J Child Neurol 2008;23:916-8. [6] Gripp KW, Hopkins E, Vinkler C, et al. Significant overlap and possible identity of macrocephaly capillary malformation and
megalencephaly, polymicrogyria-polydactyly hydrocephalus syndromes. Am J Med Genet 2009;149A:868-76. [7] Tore HG, McKinney AM, Nagar VA, Lohman B, Truwit CL, Raybaud C. Syndrome of megalencephaly, polydactyly, and polymicrogyria lacking frank hydrocephalus, with associated MR imaging findings. AJNR Am J Neuroradiol 2009;30:1620-2.
[8] Barkovich AJ. Malformations secondary to abnormal cortical organization. Polymicrogyria. In: Barkovich AJ. Pediatric neuroimaging. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2000:311-7. [9] Conway RL, Pressman BD, Dobyns WB, et al. Neuroimaging features in macrocephaly-capillary malformation syndrome, a longitudinal study of 17 patients. Am J Med Genet A 2007;143A:2981-3008.
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