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

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

› Author Affiliations

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

References
1 Mirzaa GM, Dobyns WB. The “megalencephaly-capillary malformation” (MCAP) syndrome: the nomenclature of a highly recognizable multiple congenital anomaly syndrome. Am J Med Genet A 2013; 161A (08) 2115-2116
2 Clayton-Smith J, Kerr B, Brunner H. , et al. Macrocephaly with cutis marmorata, haemangioma and syndactyly–a distinctive overgrowth syndrome. Clin Dysmorphol 1997; 6 (04) 291-302
3 Gerritsen MJ, Steijlen PM, Brunner HG, Rieu P. Cutis marmorata telangiectatica congenita: report of 18 cases. Br J Dermatol 2000; 142 (02) 366-369
4 Moore CA, Toriello HV, Abuelo DN. , et al. Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities. Am J Med Genet 1997; 70 (01) 67-73
5 Lapunzina P, Gairí A, Delicado A. , et al. Macrocephaly-cutis marmorata telangiectatica congenita: report of six new patients and a review. Am J Med Genet A 2004; 130A (01) 45-51
6 Toriello HV, Mulliken JB. Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM). Am J Med Genet A 2007; 143A (24) 3009
7 Conway RL, Pressman BD, Dobyns WB. , et al. Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients. Am J Med Genet A 2007; 143A (24) 2981-3008
8 Rivière JB, Mirzaa GM, O'Roak BJ. , et al; Finding of Rare Disease Genes (FORGE) Canada Consortium. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 2012; 44 (08) 934-940
9 Keppler-Noreuil KM, Rios JJ, Parker VE. , et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A 2015; 167A (02) 287-295
10 Ruggieri M, Polizzi A. From Aldrovandi's “Homuncio” (1592) to Buffon's girl (1749) and the “Wart Man” of Tilesius (1793): antique illustrations of mosaicism in neurofibromatosis?. J Med Genet 2003; 40 (03) 227-232
11 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
12 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
13 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: first descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet A 2018; 176 (03) 515-550
14 Ruggieri M, Praticò AD, Serra A. , et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
15 Stephan MJ, Hall BD, Smith DW, Cohen Jr MM. Macrocephaly in association with unusual cutaneous angiomatosis. J Pediatr 1975; 87 (03) 353-359
16 Mirzaa GM, Conway RL, Gripp KW. , et al. Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am J Med Genet A 2012; 158A (02) 269-291
17 Choi YC, Yum MS, Kim MJ, Lee YJ, Ko TS. Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea. Korean J Pediatr 2016; 59 (Suppl. 01) S152-S156
18 Ruggieri M, Gabriele AL, Polizzi A. , et al. Natural history of neurofibromatosis type 2 with onset before the age of 1 year. Neurogenetics 2013; 14 (02) 89-98
19 Ruggieri M, Polizzi A, Spalice A. , et al. The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 2015; 87 (05) 401-410
20 Ruggieri M, Praticò AD, Evans DGE. Diagnosis, management and new therapeutic options in childhood neurofibromatosis type 2 and related disorders. Semin Pediatr Neurol 2015; 22 (04) 240-258
21 Ruggieri M, Praticò AD, Serra A. , et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
22 Caltabiano R, Magro G, Polizzi A. , et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
23 Ruggieri M, Iannetti P, Clementi M. , et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
24 Ruggieri M. Familial hypomelanosis of ito: implications for genetic counselling. Am J Med Genet 2000; 95 (01) 82-84
25 Ruggieri M, Magro G, Ruggieri M, Polizzi A. Tumors and hypomelanosis of Ito. Arch Pathol Lab Med 2001; 125 (05) 599-601
26 Ruggieri M, Mastrangelo M, Spalice A. , et al. Bilateral (opercular and paracentral lobular) polymicrogyria and neurofibromatosis type 1. Am J Med Genet A 2011; 155A (03) 582-585
27 Pavone P, Praticò AD, Ruggieri M, Falsaperla R. Hypomelanosis of Ito: a round on the frequency and type of epileptic complications. Neurol Sci 2015; 36 (07) 1173-1180
28 Ruggieri M, Pavone P, Polizzi A. , et al. Ophthalmological manifestations in segmental neurofibromatosis type 1. Br J Ophthalmol 2004; 88 (11) 1429-1433
29 Ruggieri M, Pavone V, De Luca D, Franzò A, Tiné A, Pavone L. Congenital bone malformations in patients with neurofibromatosis type 1 (Nf1). J Pediatr Orthop 1999; 19 (03) 301-305
30 Ruggieri M, Polizzi A. Segmental neurofibromatosis. J Neurosurg 2000; 93 (03) 530-532
31 Polizzi A, Pavone P, Ciancio E, La Rosa C, Sorge G, Ruggieri M. Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediatr Endocrinol Metab 2005; 18 (10) 1019-1025
32 Pavone P, Praticò AD, Gentile G. , et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
33 Ruggieri M. Cutis tricolor: congenital hyper- and hypopigmented lesions in a background of normal skin with and without associated systemic features: further expansion of the phenotype. Eur J Pediatr 2000; 159 (10) 745-749
34 Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutières syndrome. Pediatr Neurol 2001; 24 (04) 300-302
35 Ruggieri M. Mosaic (segmental) neurofibromatosis type 1 (NF1) and type 2 (NF2): no longer neurofibromatosis type 5 (NF5). Am J Med Genet 2001; 101 (02) 178-180
36 Segal D, Heary RF, Sabharwal S, Barry MT, Ming X. Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome. J Neurosurg Pediatr 2016; 18 (01) 79-82
37 Akcar N, Adapinar B, Dinleyici C, Durak B, Ozkan IR. A case of macrocephaly-cutis marmorata telangiectatica congenita and review of neuroradiologic features. Ann Genet 2004; 47 (03) 261-265
38 Dinleyici EC, Tekin N, Aksit MA, Kilic Z, Adapinar B, Bozan G. Macrocephaly-Cutis marmorata telangiectatica congenita with atrial septal aneurysm and magnetic resonance imaging (MRI) findings. Pediatr Int 2004; 46 (03) 366-367
39 Nyberg RH, Uotila J, Kirkinen P, Rosendahl H. Macrocephaly-cutis marmorata telangiectatica congenita syndrome–prenatal signs in ultrasonography. Prenat Diagn 2005; 25 (02) 129-132
40 Mirzaa GM, Rivière JB, Dobyns WB. Megalencephaly syndromes and activating mutations in the PI3K-AKT pathway: MPPH and MCAP. Am J Med Genet C Semin Med Genet 2013; 163C (02) 122-130
41 Giuliano F, David A, Edery P. , et al. Macrocephaly-cutis marmorata telangiectatica congenita: seven cases including two with unusual cerebral manifestations. Am J Med Genet A 2004; 126A (01) 99-103
42 Ercan TE, Oztunc F, Celkan T. , et al. Macrocephaly-capillary malformation syndrome in a newborn with tetralogy of fallot and sagittal sinus thrombosis. J Child Neurol 2013; 28 (01) 115-119
43 Baralle D, Firth H. A case of the new overgrowth syndrome--macrocephaly with cutis marmorata, haemangioma and syndactyly. Clin Dysmorphol 2000; 9 (03) 209-211
44 Papetti L, Tarani L, Nicita F. , et al. Macrocephaly-capillary malformation syndrome: description of a case and review of clinical diagnostic criteria. Brain Dev 2012; 34 (02) 143-147
45 Ruggieri M, Milone P, Pavone P. , et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
46 Ruggieri M, Polizzi A, Strano S. , et al. Mixed vascular nevus syndrome: a report of four new cases and a literature review. Quant Imaging Med Surg 2016; 6 (05) 515-524
47 Barbagallo M, Ruggieri M, Incorpora G. , et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
48 Ruggieri M, D'Arrigo G, Abbate M, Distefano A, Upadhyaya M. Multiple coronary artery aneurysms in a child with neurofibromatosis type 1. Eur J Pediatr 2000; 159 (07) 477-480
49 Ruggieri M, Packer RJ. Why do benign astrocytomas become malignant in NF1?. Neurology 2001; 56 (07) 827-829
50 Ruggieri M, Polizzi A. Choroidal abnormalities and mental retardation in neurofibromatosis type 1. Lancet 2001; 357 (9252): 311-312
51 Ruggieri M, Pavone V, Tiné A. , et al. Ossifying fibroma of the skull in a patient with neurofibromatosis type 1. Case report. J Neurosurg 1996; 85 (05) 941-944
52 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
53 Ruggieri M, Iannetti F, Polizzi A. , et al. Cataracts in the setting of a newly recognised neurocutaneous malformation syndrome with cutis tricolor. Br J Ophthalmol 2009; 93: 175-176
54 Ruggieri M, Roggini M, Kennerknecht I, Polizzi A, Distefano A, Pavone V. Spectrum of skeletal abnormalities in a complex malformation syndrome with “cutis tricolor” (Ruggieri-Happle syndrome). Acta Paediatr 2011; 100 (01) 121-127
55 Nicita F, Spalice A, Roggini M. , et al. Complex malformation (Ruggieri-Happle) phenotype with “cutis tricolor” in a 10-year-old girl. Brain Dev 2012; 34 (10) 869-872
56 Ruggieri M, Polizzi A, Schepis C. , et al. Cutis tricolor: a literature review and report of five new cases. Quant Imaging Med Surg 2016; 6 (05) 525-534
57 Lionetti E, Pavone P, Kennerknecht I. , et al. Neurological manifestations in individuals with pure cutaneous or syndromic (Ruggieri-Happle syndrome) phenotypes with “cutis tricolor”: a study of 14 cases. Neuropediatrics 2010; 41 (02) 60-65
58 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langerhans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
59 Pavone P, Praticò AD, Rizzo R. , et al. A clinical review on megalencephaly: A large brain as a possible sign of cerebral impairment. Medicine (Baltimore) 2017; 96 (26) e6814
60 Pavone P, Praticò AD, Vitaliti G. , et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
61 Pavone P, Nigro F, Falsaperla R. , et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
62 Brancati F, Travaglini L, Zablocka D. , et al; International JSRD Study Group. RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders. Clin Genet 2008; 74 (02) 164-170
63 Vogels A, Devriendt K, Legius E. , et al. The macrocephaly-cutis marmorata telangiectatica congenita syndrome. Long-term follow-up data in 4 children and adolescents. Genet Couns 1998; 9 (04) 245-253
64 Cohen Jr MM, Neri G, Weksberg R. Overgrowth syndromes. Oxford Monographs on Medical Genetics. New York, NY: Oxford University Press; 2002: 206
65 Swarr DT, Khalek N, Treat J. , et al. Expanding the differential diagnosis of fetal hydrops: an unusual prenatal presentation of megalencephaly-capillary malformation syndrome. Prenat Diagn 2013; 33 (10) 1010-1012
66 Reardon W, Harding B, Winter RM, Baraitser M. Hemihypertrophy, hemimegalencephaly, and polydactyly. Am J Med Genet 1996; 66 (02) 144-149
67 Carcao M, Blaser SI, Grant RM, Weksberg R, Siegel-Bartelt J. MRI findings in macrocephaly-cutis marmorata telangiectatica congenita. Am J Med Genet 1998; 76 (02) 165-167
68 Franceschini P, Licata D, Di Cara G, Guala A, Franceschini D, Genitori L. Macrocephaly-Cutis marmorata telangiectatica congenita without cutis marmorata?. Am J Med Genet 2000; 90 (04) 265-269
69 Polizzi A, Pavone P, Iannetti P, Manfré L, Ruggieri M. Septo-optic dysplasia complex: a heterogeneous malformation syndrome. Pediatr Neurol 2006; 34 (01) 66-71
70 Ruggieri M, Tigano G, Mazzone D, Tiné A, Pavone L. Involvement of the white matter in hypomelanosis of Ito (incontinentia pigmenti achromiens). Neurology 1996; 46 (02) 485-492
71 Salpietro V, Mankad K, Kinali M. , et al. Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study. J Pediatr Endocrinol Metab 2014; 27 (1-2): 107-115
72 Garavelli L, Leask K, Zanacca C. , et al. MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature. Genet Couns 2005; 16 (02) 117-128
73 Salpietro V, Polizzi A, Di Rosa G. , et al. Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications. Int J Endocrinol 2014; 2014: 282489
74 Ruggieri M, Rizzo R, Pavone P, Baieli S, Sorge G, Happle R. Temporal triangular alopecia in association with mental retardation and epilepsy in a mother and daughter. Arch Dermatol 2000; 136 (03) 426-427
75 Matricardi S, Spalice A, Salpietro V. , et al. Epilepsy in the setting of full trisomy 18: a multicenter study on 18 affected children with and without structural brain abnormalities. Am J Med Genet C Semin Med Genet 2016; 172 (03) 288-295
76 Iannetti P, Parisi P, Spalice A, Ruggieri M, Zara F. Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. Epilepsy Res 2009; 85 (01) 89-95
77 Ruggieri M, McShane MA. Parental view of epilepsy in Angelman syndrome: a questionnaire study. Arch Dis Child 1998; 79 (05) 423-426
78 Ruggieri M, Polizzi A, Pavone L, Musumeci S. Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998; 101 (1 Pt 1): 112-119
79 Distefano G, Praticò AD. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy. Ital J Pediatr 2010; 36: 63
80 Pavone P, Falsaperla R, Ruggieri M. , et al. Clinical course of NMDAr encephalitis and effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15: 84-89
81 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
82 Sorge G, Ruggieri M, Polizzi A, Scuderi A, Di Pietro M. SHORT syndrome: a new case with probable autosomal dominant inheritance. Am J Med Genet 1996; 61 (02) 178-181
83 Robertson SP, Gattas M, Rogers M, Adès LC. Macrocephaly–cutis marmorata telangiectatica congenita: report of five patients and a review of the literature. Clin Dysmorphol 2000; 9 (01) 1-9
84 Luk HM, Lo IF, Lai CW, Yeung WL, Lam ST. Macrocephaly-capillary malformation: a report of four Chinese patients and literature review. Clin Dysmorphol 2012; 21 (02) 64-68
85 Yano S, Watanabe Y. Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome. Am J Med Genet 2001; 102 (02) 149-152
86 Kuint J, Globus O, Ben Simon GJ, Greenberger S. Macrocephaly-capillary malformation presenting with fetal arrhythmia. Pediatr Dermatol 2012; 29 (03) 384-386
87 Howells R, Curran A, Jardine P, Newbury-Ecob R, Sandhu B. Mesenteric angina complicating a mesodermal anomaly. Eur J Paediatr Neurol 2000; 4 (04) 181-183
88 Mégarbané A, Haddad J, Lyonnet S, Clayton-Smith J. Child with overgrowth, pigmentary streaks, polydactyly, and intestinal lymphangiectasia: macrocephaly-cutis marmorata telangiectatica congenita syndrome or new disorder?. Am J Med Genet A 2003; 116A (02) 184-187
89 Thong MK, Thompson E, Keenan R. , et al. A child with hemimegalencephaly, hemihypertrophy, macrocephaly, cutaneous vascular malformation, psychomotor retardation and intestinal lymphangiectasia--a diagnostic dilemma. Clin Dysmorphol 1999; 8 (04) 283-286
90 Trifiletti RR, Incorpora G, Polizzi A, Cocuzza MD, Bolan EA, Parano E. Aicardi syndrome with multiple tumors: a case report with literature review. Brain Dev 1995; 17 (04) 283-285
91 Spalice A, Ruggieri M, Grosso S. , et al. Dysembryoplastic neuroepithelial tumors: a prospective clinicopathologic and outcome study of 13 children. Pediatr Neurol 2010; 43 (06) 395-402
92 Schwartz IV, Felix TM, Riegel M, Schüler-Faccini L. Atypical macrocephaly-cutis marmorata telangiectatica congenita with retinoblastoma. Clin Dysmorphol 2002; 11 (03) 199-202
93 Cohen Jr MM. A comprehensive and critical assessment of overgrowth and overgrowth syndromes. In Harris H, Hirschhorn K. , eds: “Advances in Human Genetics”. Vol. 18. New York: Plenum Press; 1989: 181-303 and 373–376
94 Lederer D, Rack K, Boulanger S, Battisti O, Verellen-Dumoulin C. Discordant monozygotic twins for macrocephaly-capillary malformation. Am J Med Genet A 2012; 158A (06) 1509-1511
95 Kok K, Nock GE, Verrall EA. , et al. Regulation of p110delta PI 3-kinase gene expression. PLoS One 2009; 4 (04) e5145
96 Loconte DC, Grossi V, Bozzao C. , et al. Molecular and functional characterization of three different postzygotic mutations in PIK3CA-related overgrowth spectrum (PROS) patients: effects on PI3K/AKT/mTOR signaling and sensitivity to PIK3 inhibitors. PLoS One 2015; 10 (04) e0123092
97 Ruggieri M, Praticò AD. Mosaic neurocutaneous disorders and their causes. Semin Pediatr Neurol 2015; 22 (04) 207-233
98 Negishi Y, Miya F, Hattori A. , et al. A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. BMC Med Genet 2017; 18 (01) 4
99 McDermott JH, Byers H, Clayton-Smith J. Detection of a mosaic PIK3CA mutation in dental DNA from a child with megalencephaly capillary malformation syndrome. Clin Dysmorphol 2016; 25 (01) 16-18
100 Kurek KC, Luks VL, Ayturk UM. , et al. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet 2012; 90 (06) 1108-1115
101 Lindhurst MJ, Parker VE, Payne F. , et al. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet 2012; 44 (08) 928-933
102 Rios JJ, Paria N, Burns DK. , et al. Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly. Hum Mol Genet 2013; 22 (03) 444-451
103 Orloff MS, He X, Peterson C. , et al. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet 2013; 92 (01) 76-80
104 Wright DR, Frieden IJ, Orlow SJ. , et al. The misnomer “macrocephaly-cutis marmorata telangiectatica congenita syndrome”: report of 12 new cases and support for revising the name to macrocephaly-capillary malformations. Arch Dermatol 2009; 145 (03) 287-293
105 Papetti L, Tarani L, Nicita F. , et al. Macrocephaly-capillary malformation syndrome: description of a case and review of clinical diagnostic criteria. Brain Dev 2012; 34 (02) 143-147
106 Mirzaa G, Dodge NN, Glass I. , et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures. Neuropediatrics 2004; 35 (06) 353-359
107 Colombani M, Chouchane M, Pitelet G. , et al. A new case of megalencephaly and perisylvian polymicrogyria with post-axial polydactyly and hydrocephalus: MPPH syndrome. Eur J Med Genet 2006; 49 (06) 466-471
108 Garavelli L, Guareschi E, Errico S. , et al. Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): report of a new case. Neuropediatrics 2007; 38 (04) 200-203
109 Pisano T, Meloni M, Cianchetti C, Falchi M, Nucaro A, Pruna D. Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome: a new case with syndactyly. J Child Neurol 2008; 23 (08) 916-918
110 Gripp KW, Hopkins E, Vinkler C. , et al. Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes. Am J Med Genet A 2009; 149A (05) 868-876
111 Kariminejad A, Radmanesh F, Rezayi AR, Tonekaboni SH, Gleeson JG. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome: a case report. J Child Neurol 2013; 28 (05) 651-657
112 Demir N, Peker E, Gülşen I, Kaba S, Tuncer O. Megalencephaly, polymicrogyria, polydactyly and hydrocephalus (MPPH) Syndrome: a new case with occipital encephalocele and cleft palate. Genet Couns 2015; 26 (04) 381-385
113 Nellist M, Schot R, Hoogeveen-Westerveld M. , et al. Germline activating AKT3 mutation associated with megalencephaly, polymicrogyria, epilepsy and hypoglycemia. Mol Genet Metab 2015; 114 (03) 467-473
114 Barnicoat A, Salman M, Chitty L, Baraitser M. A distinctive overgrowth syndrome with polysyndactyly. Clin Dysmorphol 1996; 5 (04) 339-346
115 López-Herce Cid J, Roche Herrero MC, Pascual-Castroviejo I. Cutis marmorata telangiectática congénita. Anomalías asociadas. [Article in English]. An Esp Pediatr 1985; 22 (08) 575-580
116 Meyer E. Neurocutaneous syndrome with excessive macrohydrocephalus. (Sturge-Weber/Klippel-Trenaunay syndrome). Neuropadiatrie 1979; 10 (01) 67-75
117 Moffitt DL, Kennedy CT, Newbury-Ecob R. What syndrome is this? Macrocephaly with cutis marmorata, hemangioma, and syndactyly syndrome. Pediatr Dermatol 1999; 16 (03) 235-237
118 Ringrose RE, Jabbour JT, Keele DK. Hemihypertrophy. Pediatrics 1965; 36 (03) 434-448
119 Harada A, Miya F, Utsunomiya H. , et al. Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3. Childs Nerv Syst 2015; 31 (03) 465-471
120 Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet
121 Mitha AP, Bullivant KJ, Lauzon JL, Hader WJ. Endoscopic third ventriculostomy to treat hydrocephalus associated with macrocephaly-cutis marmorata telangiectatica congenita. J Neurosurg Pediatr 2009; 4 (04) 397-401
122 Martínez-Lage JF, Guillén-Navarro E, Almagro MJ, Felipe-Murcia M, López López-Guerrero A, Galarza M. Hydrocephalus and Chiari type 1 malformation in macrocephaly-cutis marmorata telangiectatica congenita: a case-based update. Childs Nerv Syst 2010; 26 (01) 13-18
123 Keppler-Noreuil KM, Sapp JC, Lindhurst MJ. , et al. Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum. Am J Med Genet A 2014; 164A (07) 1713-1733