How to cite this article: Gripp KW, Hopkins E, Vinkler C, Lev D, Malinger G, Lerman-Sagie T, Dobyns WB. 2009. Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes. Am J Med Genet Part A 149A:868–876.
Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes†
Article first published online: 7 APR 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 5, pages 868–876, May 2009
How to Cite
Gripp, K. W., Hopkins, E., Vinkler, C., Lev, D., Malinger, G., Lerman-Sagie, T. and Dobyns, W. B. (2009), Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes. Am. J. Med. Genet., 149A: 868–876. doi: 10.1002/ajmg.a.32732
- Issue published online: 23 APR 2009
- Article first published online: 7 APR 2009
- Manuscript Accepted: 17 DEC 2008
- Manuscript Received: 18 NOV 2008
- congenital heart disease;
We report on three patients with macrocephaly and polymicrogyria, and additional anomalies seen in megalencephaly polymicrogyria-polydactyly hydrocephalus (MPPH) and macrocephaly capillary malformation (MCM) syndromes. Based on their characteristic brain malformations they were originally diagnosed with MPPH. In one patient the phenotype evolved during early infancy, and ultimately resulted in a diagnosis of MCM. A second was prenatally diagnosed with MPPH, but postnatally visualized capillary malformations led to a diagnosis of MCM. In a third, the original MPPH diagnosis was reconsidered after a critical review revealed additional subtle findings suggestive of MCM. Characteristic brain malformations are thought to distinguish between MPPH with perisylvian polymicrogyria, and MCM with megalencephaly with Chiari 1 malformation. However, polymicrogyria was reported in a significant number of patients with MCM. Conversely, upon review of imaging studies of patients with MPPH, we noted progressive crowding of the posterior fossa and acquired tonsillar herniation, a process deemed characteristic for MCM. Thus, neither polymicrogyria nor acquired tonsillar herniation are distinguishing features, and occur in both disorders. In addition to brain abnormalities, shared findings include cognitive impairment, coarse facial features and postaxial polydactyly. Facial nevus flammeus and cutis marmorata are most noticeable in infancy, and ligamentous laxity and redundant soft tissue are somewhat subjective findings. While asymmetric overgrowth is considered typical for MCM, it is not universally present. These variable and subtle findings can be identified in patients with MPPH. We propose that MPPH and MCM may not represent distinct entities and that the term MPPH-CM syndrome be used to describe this spectrum. © 2009 Wiley-Liss, Inc.