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

Andrea D. Praticò
1   Unit 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
2   Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
,
Agata Polizzi
3   Institute of Neurological Sciences, National Research Council, Catania, Italy
,
Stefania Salafia
4   Unit of Pediatrics, Lentini Hospital, Lentini, Italy
,
Elena R. Praticò
5   Unit of Pediatrics, Carpi Hospital, Carpi, Italy
,
Maria Teresa Garozzo
1   Unit 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
1   Unit 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
1   Unit 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
6   Unit of Paediatric Radiology, AOU “Policlinico-Vittorio Emanuele,” Catania, Italy
,
Concetta Pirrone
7   Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
,
Antonio Zanghì
8   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania Italy
,
Agata Fiumara
9   Unit of Clinical Pediatrics, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Martino Ruggieri
1   Unit 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
10   Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro,” Bari, Italy
› Author Affiliations
Further Information

Publication History

05 January 2018

05 May 2018

Publication Date:
20 August 2018 (online)

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.

 
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