Neuroimaging findings in macrocephaly–capillary malformation: A longitudinal study of 17 patients
ABSTRACT Here, we report the neuroimaging findings and neurological changes in 17 unpublished patients with Macrocephaly-Capillary Malformation (M-CM). This syndrome has been traditionally known as Macrocephaly-Cutis Marmorata Telangiectatica Congenita (M-CMTC), but we explain why M-CM is a more accurate term for this overgrowth syndrome. We analyzed the 17 patients with available brain MRI or CT scans and compared their findings with features identified by a comprehensive review of published cases. White matter irregularities with increased signal on T2-weighted images were commonly observed findings. A distinctive feature in more than half the patients was cerebellar tonsillar herniation associated with rapid brain growth and progressive crowding of the posterior fossa during infancy. In four such cases, we confirmed that the tonsillar herniation was an acquired event. Concurrently, with the development of these findings, ventriculomegaly (frequently obstructive) and dilated dural venous sinuses were observed in conjunction with prominent Virchow-Robin spaces in many of those in whom cerebellar tonsil herniation had developed. We postulate that this constellation of unusual features suggests a dynamic process of mechanical compromise in the posterior fossa, perhaps initiated by a rapidly growing cerebellum, which leads to congestion of the venous drainage with subsequently compromised cerebrospinal fluid reabsorption, all of which increases the posterior fossa pressure and leads to acquired tonsillar herniation. We make a distinction between congenital Chiari I malformation and acquired cerebellar tonsil herniation in this syndrome. We also observed numerous examples of abnormal cortical morphogenesis, including focal cortical dysplasia, polymicrogyria which primarily involved the perisylvian and insular regions, and cerebral and/or cerebellar asymmetric overgrowth. Other findings included a high frequency of cavum septum pellucidum or vergae, thickened corpus callosum, prominent optic nerve sheaths and a single case of venous sinus thrombosis. One patient was found to have a frontal perifalcine mass resembling a meningioma at age 5 years. This is the second apparent occurrence of this specific tumor in M-CM.
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ABSTRACT: Overgrowth syndromes can be associated with asymmetry, obesity and various vascular malformations. Macrocephaly-Capillary Malformation (M-CM) is a more recently defined overgrowth syndrome characterized by cutaneous capillary malformation occurring in association with macrocephaly with tendency to progressive enlargement, abnormalities of somatic growth with body asymmetry including brain asymmetry, developmental delay, typical face with full cheeks, nevus flammeus of the nose and/or philtrum and upper lip, joint laxity, thickened subcutaneous tissue and 2/3 syndactyly of the toes. We evaluated three patients who demonstrated characteristic features of the disorder. Patients seen in the Genetic clinic of a tertiary care center were subjects of the analysis. We present three cases of overgrowth syndrome with common features of macrocephaly, capillary malformation, dysmorphic face and abnormal neurocognitive profile. These features are consistent with the newly defined M-CM syndrome. This condition must be differentiated from other overgrowth syndromes for appropriate surveillance for known complications and genetic counseling. We discuss the diagnostic criteria for the disorder and also recommend to include typical face with full cheeks, nevus flammeus of the nose and/or philtrum and upper lip, considering it as minor criterion on the basis of findings in present cases. One of the cases had bluish white iris which has not been described earlier.Journal of the neurological sciences 02/2012; 313(1-2):178-81. DOI:10.1016/j.jns.2011.09.039 · 2.26 Impact Factor
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ABSTRACT: Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear. Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation. Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.Child s Nervous System 11/2014; DOI:10.1007/s00381-014-2589-y · 1.16 Impact Factor
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ABSTRACT: Central nervous system anomalies in Pfeiffer syndrome (PS) due to mutations in the FGFR2 gene are poorly understood, even though PS is often associated with serious cognitive impairment. The aim of this study is to describe the neuropathological phenotype in PS. We present four severe fetal cases of sporadic PS with FGFR2 mutations who underwent termination followed by fetopathological and neuropathological examination. We studied the expression pattern of Fgfr2 in the mouse brain using radioactive fluorescence in situ hybridization. PS is associated with brain deformations due to the abnormal skull shape, but FGFR2 mutations also induce specific brain developmental anomalies: megalencephaly, midline disorders, amygdala, and hippocampus malformations, and ventricular wall alterations. The expression pattern of Fgfr2 in mice matches the distribution of malformations in humans. The brain anomalies in PS result from the combination of mechanical deformations and intrinsic developmental disorders due to FGFR2 hyperactivity. Several similarities are noted between these anomalies and the brain lesions observed in other syndromes due to mutations in FGF-receptor genes. The specific involvement of the hippocampus and the amygdala should encourage the precise cognitive screening of patients with mild forms of PS. © 2012 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 11/2012; 158A(11):2797-806. DOI:10.1002/ajmg.a.35598 · 2.05 Impact Factor