Megalencephaly‐capillary malformation (MCAP) and megalencephaly‐polydactyly‐polymicrogyria‐hydrocephalus (MPPH) syndromes: Two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis

Abstract

The macrocephaly-capillary malformation syndrome (M-CM), which we here propose to rename the megalencephaly-capillary malformation syndrome (MCAP; alternatively the megalencephalycapillary malformation-polymicrogyria syndrome), and the more recently described megalencephaly-polymicrogyriapolydactyly-hydrocephalus syndrome (MPPH) are two megalencephaly (MEG) disorders that involve a unique constellation of physical and neuroimaging anomalies. We compare the features in 42 patients evaluated for physical and neuroimaging characteristics of MCAP and MPPH and propose a more global view of these syndromes based on classes of developmental abnormalities that include primary MEG and growth dysregulation, developmental vascular anomalies (primarily capillary malformations), distal limb anomalies (such as syndactyly and polydactyly), cortical brain malformations (most distinctively polymicrogyria, PMG), and variable connective tissue dysplasia. Based on these classes of developmental abnormalities, we propose that MCAP diagnostic criteria include progressive How to Cite this Article:

De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia

“…In fact, atypical absences, myoclonic jerks, generalized tonic-clonic or complex febrile seizures are reported in these individuals. 5,14 Our patient showed focal seizures characterized by dyscognitive features with a critical onset in the right hemisphere. As described in asymmetrical bilateral PMG, our case had epilepsy laterality with more severe and difficult-to-treat seizures.…”

“…14 Other patterns occur such as focal PMG or PMG involving bilateral frontal lobes. 1, 14 Although the extent of PMG involvement is bilateral, many patients show a mildly asymmetric presentation, as observed in our case.…”

“…14 Other patterns occur such as focal PMG or PMG involving bilateral frontal lobes. 1, 14 Although the extent of PMG involvement is bilateral, many patients show a mildly asymmetric presentation, as observed in our case. 5 The proband's brain MRI revealed PMG with broad cerebral involvement extending to the frontoparietal cortex; in addition a sulcus with cortical-white matter blurring in the anterior right insula and abnormal white matter signal in right anterolateral temporal lobe, and an infolding of thick cortex with cortical blurring in the right frontal operculum are consistent with FCD, 15 a malformation not yet described in MPPH.…”

Hemihypertrophy Spectrum

“…MCAP is characterized by primary megalencephaly, prenatal overgrowth, brain and body asymmetry, digital anomalies consisting of syndactyly with or without postaxial polydactyly, cutaneous vascular malformations, connective tissue dysplasia involving the skin, joints and subcutaneous tissue, and cortical brain malformations, most commonly polymicrogyria [11,12]. This disorder is also known as the macrocephaly-capillary malformation (MCM) syndrome [13].…”

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

“…It has first been described as macrocephaly-cutis marmorata (M-CM) teleangiectatica syndrome in 1997 1,2 and been renamed in 2007 to M-CM syndrome. 3 In order to reflect the very large brain size-rather than simply a large head-Mirzaa et al 4 proposed to re-rename the syndrome as MCAP syndrome, which is the current nomenclature until today.…”