Mixed Vascular Nevus Syndrome

Martino Ruggieri; Agata Polizzi; Chiara Maria Battaglini; Andrea D. Praticò; Stefania Tomarchio; Flavia La Mendola; Domenico A. Restivo; Pietro Milone; Concetta Pirrone; Elena Commodari; Antonio Zanghì; Carmelo Schepis; Francesco Lacarrubba; Giuseppe Micali

doi:10.1055/s-0038-1667150

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2018; 16(05): 282-287
DOI: 10.1055/s-0038-1667150

Review Article

Georg Thieme Verlag KG Stuttgart · New York

Mixed Vascular Nevus Syndrome

Martino Ruggieri

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

,

Agata Polizzi

²Institute of Neurological Sciences, National Research Council, Catania, Italy

,

Chiara Maria Battaglini

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

,

Andrea D. Praticò

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

³Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom

,

Stefania Tomarchio

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

,

Flavia La Mendola

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

,

Domenico A. Restivo

⁴Neurologic Unit, Department of Internal Medicine, Nuovo “Garibaldi” Hospital, Catania, Italy

,

Pietro Milone

⁵Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Section of Radiology, University of Catania, Catania, Italy

,

Concetta Pirrone

⁶Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy

,

Elena Commodari

⁶Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy

,

Antonio Zanghì

⁷Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy

,

Carmelo Schepis

⁸Unit of Dermatology, Oasi Research Institute - IRCCS, Troina, Enna, Italy

,

Francesco Lacarrubba

⁹Dermatology Clinic, University of Catania, Catania, Italy

,

Giuseppe Micali

⁹Dermatology Clinic, University of Catania, Catania, Italy

› Author Affiliations

Abstract

Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as a purely cutaneous trait or as a hallmark of a neurocutaneous phenotype, the so-called mixed vascular nevus syndrome. The latter is characterized by the combination of paired vascular twin nevi and brain abnormalities of the Dyke–Davidoff–Masson type, consisting of crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels, and homolateral hypertrophy of the skull and sinuses (hyperpneumatization) with contralateral hemispheric hypertrophy. In other cases, the paired vascular twin nevi and brain malformations of the Dyke–Davidoff–Masson type occur in association with systemic abnormalities consisting of facial asymmetry, skeletal anomalies, and disorders of autoimmunity. In 2014, Happle proposed to name the syndrome with the eponym Ruggieri–Leech's syndrome after the first two authors who reported (independently) this phenotype in different patients.

Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatization versus hypertrophy and brain megalencephaly/colpocephaly versus cortical dysplasia.

Keywords

mixed vascular nevus - nevus vascularis mixtus - mixed vascular nevus syndrome - telangiectatic nevus - nevus anemicus - Dyke–Davidoff–Masson syndrome - MRI - CT - ultrasound - EEG

Full Text

References

References
1 Hamm H, Happle R. Naevus vascularis mixtus. Bericht über 4 Beobachtungen. Hautarzt 1986; 37 (07) 388-392
2 Happle R. Mosaicism in Human Skin: Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin: Springer-Verlag; 2014
3 Happle R. Capillary malformations: a classification using specific names for specific skin disorders. J Eur Acad Dermatol Venereol 2015; 29 (12) 2295-2305
4 Happle R. The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet A 2016; 170A (02) 452-459
5 Di Lernia V, Valeri F, Patrizi A. What is your diagnosis? Naevus vascularis mixtus [in French]. Ann Dermatol Venereol 1990; 117 (6–7): 469-470
6 Ruggieri M, Praticò AD. Mosaic neurocutaneous disorders and their causes. Semin Pediatr Neurol 2015; 22 (04) 207-233
7 Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis type IVa. Arch Dermatol 1985; 121 (05) 651-655
8 Enjolras O, Mulliken JB. Vascular malformations. In: Harper J, Oranje A, Prose N. , eds. Textbook of Dermatology. Oxford: Blackwell Science; 2000: 975-976
9 Happle R. Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 2005; 141 (03) 385-388
10 Happle R. , ed. Didymotic skin disorders. In: Mosaicism in Human Skin. Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin: Springer-Verlag; 2014: 109-114
11 Leech SN, Taylor AE, Ramesh V, Birchall D, Ann Lynch S. Widespread capillary malformation associated with global developmental delay and megalencephaly. Clin Dysmorphol 2004; 13 (03) 169-172
12 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
13 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
14 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
15 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
16 Ruggieri M, Packer RJ. Why do benign astrocytomas become malignant in NF1?. Neurology 2001; 56 (07) 827-829
17 Ruggieri M, Polizzi A. Choroidal abnormalities and mental retardation in neurofibromatosis type 1. Lancet 2001; 357 (9252): 311-312
18 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
19 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
20 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
21 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
22 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
23 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
24 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
25 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
26 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
27 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
28 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
29 Ruggieri M, Iannetti P, Clementi M. , et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
30 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
31 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
32 Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999; 41 (2 Pt 1): 143-164
33 Happle R. Dohi Memorial Lecture. New aspects of cutaneous mosaicism. J Dermatol 2002; 29 (11) 681-692
34 Arora R, Rani JY. Dyke-Davidoff-Masson syndrome: imaging features with illustration of two cases. Quant Imaging Med Surg 2015; 5 (03) 469-471
35 Pavone P, Nigro F, Falsaperla R. , et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
36 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
37 Pavone P, Praticò AD, Vitaliti G. , et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
38 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
39 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
40 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
41 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
42 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
43 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
44 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
45 Savasta S, Ruggieri M, Pavone P. , et al. Microcephaly associated with Legg-Calvè-Perthes disease in two siblings. Neurol Sci 2012; 33 (06) 1401-1405
46 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
47 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
48 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
49 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
50 Pavone P, Falsaperla R, Ruggieri M. , et al. Clinical course of NMDAr encephalitis and effectiveness of cyclosphosphamide treatment. J Pediatr Neurol 2017; 15: 84-89
51 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
52 Salpietro V, Polizzi A, Bertè LF. , et al. Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis. Neuroendocrinol Lett 2012; 33 (06) 569-573
53 O'Connor KC, Lopez-Amaya C, Gagne D. , et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010; 223 (1-2): 92-99
54 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
55 Hall BD, Cadle RG, Morrill-Cornelius SM, Bay CA. Phakomatosis pigmentovascularis: implications for severity with special reference to Mongolian spots associated with Sturge-Weber and Klippel-Trenaunay syndromes. Am J Med Genet A 2007; 143A (24) 3047-3053
56 Vidaurri-de la Cruz H, Tamayo-Sánchez L, Durán-McKinster C, Orozco-Covarrubias MdeL, Ruiz-Maldonado R. Phakomatosis pigmentovascularis II A and II B: clinical findings in 24 patients. J Dermatol 2003; 30 (05) 381-388
57 Fernández-Guarino M, Boixeda P, de Las Heras E, Aboin S, García-Millán C, Olasolo PJ. Phakomatosis pigmentovascularis: clinical findings in 15 patients and review of the literature. J Am Acad Dermatol 2008; 58 (01) 88-93
58 Ruggieri M. Familial hypomelanosis of Ito: implications for genetic counselling. Am J Med Genet 2000; 95 (01) 82-84
59 Ruggieri M, Magro G, Ruggieri M, Polizzi A. Tumors and hypomelanosis of Ito. Arch Pathol Lab Med 2001; 125 (05) 599-601
60 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
61 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
62 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
63 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
64 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
65 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
66 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
67 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
68 Restivo DA, Milone P. Teaching NeuroImages: progressive facial hemiatrophy (Parry-Romberg syndrome) with ipsilateral cerebral hemiatrophy. Neurology 2010; 74 (03) e11
69 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
70 Praticò AD, Pavone P, Scuderi MG. , et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
71 Comi A. Current therapeutic options in Sturge-Weber syndrome. Semin Pediatr Neurol 2015; 22 (04) 295-301
72 Lionetti E, Francavilla R, Maiuri L. , et al. Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue. J Pediatr Gastroenterol Nutr 2009; 49 (02) 202-207
73 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
74 Pavone P, Rizzo R, Conti I. , et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 2012; 25 (04) 1083-1091