Megalencephaly Capillary Malformation Syndrome

Andrea D. Praticò; Agata Polizzi; Stefania Salafia; Elena R. Praticò; Maria Teresa Garozzo; Federica Sullo; Stefano Catanzaro; Giuseppe Belfiore; Concetta Pirrone; Antonio Zanghì; Agata Fiumara; Martino Ruggieri; Nicoletta Resta

doi:10.1055/s-0038-1667010

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2018; 16(05): 328-337
DOI: 10.1055/s-0038-1667010

Review Article

Georg Thieme Verlag KG Stuttgart · New York

Megalencephaly Capillary Malformation Syndrome

Authors

Andrea D. Praticò

¹Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy

²Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
Agata Polizzi

³Institute of Neurological Sciences, National Research Council, Catania, Italy
Stefania Salafia

⁴Unit of Pediatrics, Lentini Hospital, Lentini, Italy
Elena R. Praticò

⁵Unit of Pediatrics, Carpi Hospital, Carpi, Italy
Maria Teresa Garozzo

¹Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Federica Sullo

¹Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Stefano Catanzaro

¹Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Giuseppe Belfiore

⁶Unit of Paediatric Radiology, AOU “Policlinico-Vittorio Emanuele,” Catania, Italy
Concetta Pirrone

⁷Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
Antonio Zanghì

⁸Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania Italy
Agata Fiumara

⁹Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Martino Ruggieri

¹Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Nicoletta Resta

¹⁰Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro,” Bari, Italy

Abstract

Megalencephaly capillary malformation polymicrogyria (MCAP) syndrome is characterized by the sporadic occurrence of congenital and progressive megalencephaly, brain malformations including polymicrogyria, pre- and postnatal overgrowth with body asymmetry, cutaneous vascular malformations (including capillary malformation and cutis marmorata), digital anomalies connective tissue dysplasia (including skin and joint laxity), and developmental delay. In the past 10 years, the specific cause of the disease has been found in gain-of-function mutations of PIK3CA gene, mostly somatic/postzygotic but in rare cases also de novo germline. Such gene encodes for PI3K, a critical member of the PI3K-AKT-mTOR pathway: genetic changes lead to an over-activation of this signaling system, with increased vascular, limb, and brain cell development, progression, and survival. Interestingly, mutations in the same gene can cause other clinically heterogeneous syndromes, including CLOVE syndrome, macrodactyly, focal adipose overgrowth, epidermal nevi, facial infiltrating lipomatosis: all these syndromes (even if heterogeneous) are now considered a unique spectrum, known as PIK3CA-related overgrowth syndrome. On the contrary, a disease strictly similar to MCAP, characterized by megalencephaly, polymicrogyria, polydactyly, and hydrocephalus has been found to be caused by mutations in two other PI3K-AKT-mTOR-releted genes, AKT3 and PIK3R2, and for this reason is not included in the upper mentioned group of syndromes. With the exception of neurosurgery strategies for hydrocephalus and posterior fossa overcrowding, therapeutic options are nowadays limited, even if gene-targeted treatment protocols have been proposed and protocols with such agents (i.e., Arq092) are currently ongoing in small groups of patients with promising results.

Keywords

megalencephaly - polymicrogyria - capillary malformations - hydrocephalus - AKT-PI3K-mTOR - developmental delay

Full Text

References

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