Neuropediatrics 2004; 35(6): 353-359
DOI: 10.1055/s-2004-830497
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus: A Rare Brain Malformation Syndrome Associated with Mental Retardation and Seizures

G. Mirzaa1 , N. N. Dodge2 , I. Glass3 , C. Day4 , K. Gripp5 , L. Nicholson5 , V. Straub6 , T. Voit6 , W. B. Dobyns7
  • 1Arabian Gulf University, College of Medicine and Medical Sciences, Manama, Bahrain
  • 2Department of Pediatrics, Texas Scottish Rite Hospital, Dallas, Texas, USA
  • 3Department of Pediatrics, Division of Medical Genetics, University of Washington School of Medicine, Seattle, Washington, USA
  • 4Division of Genetics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • 5DuPont de Nemours Institute, Providence, Rhode Island, USA
  • 6Department of Pediatrics and Pediatric Neurology, University of Essen, Essen, Germany
  • 7Departments of Human Genetics, Neurology and Pediatrics, The University of Chicago, Chicago, Illinois, USA
Further Information

Publication History

Received: October 8, 2004

Accepted after Revision: November 3, 2004

Publication Date:
03 January 2005 (online)


Background and Objective: Megalencephaly (MEG) or enlarged brain occurs as a mild familial variant with normal brain structure, but otherwise is an uncommon human brain malformation that may be associated with significant developmental and neurological problems. It has been classified into anatomic and metabolic subtypes. The clinical findings associated with anatomic megalencephaly have been variable and few distinct subtypes have been described. We report five unrelated children with severe congenital MEG associated with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD).

Methods: The clinical records and brain MRI of five patients have been reviewed.

Results: All patients had striking MEG that was symmetric in three of the five patients, and mildly asymmetric in two. The birth OFC was between + 2 and + 4 SD. The gyral pattern was irregular with microgyri typical of PMG, which was most severe in the perisylvian region in all five patients. Four of the five had hydrocephalus treated with a shunt. Subsequently, one of the shunted patients had small ventricles while the others had mildly to moderately enlarged lateral ventricles. Three of the five patients had postaxial polydactyly of all four limbs. The corpus callosum was dysmorphic in one patient with a fused rostrum and genu, and intact although mildly thin in the others. None were abnormally thick. All patients had severe mental retardation; three had seizures and another had an epileptiform EEG.

Conclusion: We believe this constellation of findings (MEG-PMG-POLY-HYD) comprises a new and distinct malformation syndrome that we designate the MPPH syndrome.


MD William B. Dobyns

The University of Chicago
Department of Human Genetics · Room 319 CLSC

920 E. 58th Street

Chicago, Illinois 60637


Email: [email protected]