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Here, we report the neuroimaging findings and neurological changes in 17 unpublished patients with Macrocephaly-Capillary Malformation (M-CM).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.

Diffusion Imaging of the Congenitally Thickened Corpus Callosum

“…Syndromic conditions associated with enlargement of the corpus callosum include NF type 1, Cohen syndrome, and M-CMTC. [18][19][20] In NF type 1, the large commissural tracts may result from a lack of the normal postnatal apoptotic cell pruning documented in the young rhesus monkey and in mice. 21,22 Cohen syndrome is characterized by failure to thrive, early-onset hypotonia, microcephaly, moderate-to-profound psychomotor retardation, and typical facial features.…”

“…19 M-CMTC is a rare congenital syndrome of unknown etiology associated with enlargement of a portion or the entire corpus callosum. 20 Neuroimaging in this rare disorder has shown cerebellar tonsillar herniation associated with rapid brain growth and progressive crowding of the posterior fossa during infancy along with focal cortical dysplasia, polymicrogyria primarily involving the periSylvian and insular regions, and cerebral and/or cerebellar asymmetric overgrowth. 20 None of the 4 cases reported herein had other clinical or imaging stigmata of NF type 1, microcephaly, or evidence of M-CMTC, though 1 subject did have bifrontal and peri-Sylvian polymicrogyria.…”

Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome

“…The patient presented in this report had impressive intracranial capillary vascular malformations; these malformations have not been previously reported, although there are reports of other internal vascular anomalies 10 and dilated transverse sinus. 2 Chiari I malformations are not a diagnostic criterion of MCAP. However, they have been reported in this disorder as a result of brain overgrowth.…”

Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP) - pure coincidence?

“…For example, in MCAP syndrome, many benign vascular tumors (described as hemangiomas, angiomata and angiomyolipomas), 5 but also two meningeomas, 1,18 as well as a few malignant tumors have been reported (two children with Wilms tumor 19,20 and leukemia in an 18-year-old 1 ).…”