Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.
The macrocephaly-capillary malformation syndrome (M-CM), which we here propose to rename the megalencephaly-capillary malformation syndrome (MCAP; alternatively the megalencephaly-capillary malformation-polymicrogyria syndrome), and the more recently described megalencephaly-polymicrogyria-polydactyly-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 MEG with either vascular anomalies or syndactyly. In parallel, we propose that MPPH diagnostic criteria include progressive MEG and PMG, absence of the vascular anomalies and syndactyly characteristic of MCAP, and absence of brain heterotopia.
Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA. gmirzaa@bsd.uchicago
Ghayda M
GM
Mirzaa
Robert L
RL
Conway
Karen W
KW
Gripp
Tally
T
Lerman-Sagie
Dawn H
DH
Siegel
Linda S
LS
deVries
Dorit
D
Lev
Nancy
N
Kramer
Elizabeth
E
Hopkins
John M
JM
Graham
William B
WB
Dobyns
D001921:Brain / Q000254:growth & development / Q000473:pathology*; D002196:Capillaries / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003240:Connective Tissue Diseases / Q000175:diagnosis* / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000175:diagnosis / Q000473:pathology*; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D054220:Malformations of Cortical Development / Q000175:diagnosis / Q000473:pathology; D058627:Megalencephaly / Q000145:classification / Q000175:diagnosis* / Q000473:pathology*; D009024:Morphogenesis; D059906:Neuroimaging / Q000379:methods; D017689:Polydactyly / Q000175:diagnosis / Q000473:pathology; D013576:Syndactyly / Q000175:diagnosis / Q000473:pathology