Download PDF
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
1   Unit 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
2   Institute of Neurological Sciences, National Research Council, Catania, Italy
,
Chiara Maria Battaglini
1   Unit 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
1   Unit 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
3   Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
,
Stefania Tomarchio
1   Unit 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
1   Unit 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
4   Neurologic Unit, Department of Internal Medicine, Nuovo “Garibaldi” Hospital, Catania, Italy
,
Pietro Milone
5   Department of Medical and Surgical Sciences and Advanced Technologies “G.F. Ingrassia,” Section of Radiology, University of Catania, Catania, Italy
,
Concetta Pirrone
6   Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
,
Elena Commodari
6   Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
,
Antonio Zanghì
7   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
,
Carmelo Schepis
8   Unit of Dermatology, Oasi Research Institute - IRCCS, Troina, Enna, Italy
,
Francesco Lacarrubba
9   Dermatology Clinic, University of Catania, Catania, Italy
,
Giuseppe Micali
9   Dermatology Clinic, University of Catania, Catania, Italy
› Author Affiliations
Further Information

Publication History

29 December 2017

30 April 2018

Publication Date:
20 August 2018 (online)

Also available at
    Permissions and Reprints

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
 

  • References

  • 1 Hamm H, Happle R. Naevus vascularis mixtus. Bericht über 4 Beobachtungen. Hautarzt 1986; 37 (07) 388-392
    PubMedSearch in Google Scholar
  • 2 Happle R. Mosaicism in Human Skin: Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin: Springer-Verlag; 2014
    Search in Google Scholar
  • 3 Happle R. Capillary malformations: a classification using specific names for specific skin disorders. J Eur Acad Dermatol Venereol 2015; 29 (12) 2295-2305
    CrossrefPubMedSearch in Google Scholar
  • 4 Happle R. The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet A 2016; 170A (02) 452-459
    PubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 6 Ruggieri M, Praticò AD. Mosaic neurocutaneous disorders and their causes. Semin Pediatr Neurol 2015; 22 (04) 207-233
    CrossrefPubMedSearch in Google Scholar
  • 7 Hasegawa Y, Yasuhara M. Phakomatosis pigmentovascularis type IVa. Arch Dermatol 1985; 121 (05) 651-655
    CrossrefPubMedSearch in Google Scholar
  • 8 Enjolras O, Mulliken JB. Vascular malformations. In: Harper J, Oranje A, Prose N. , eds. Textbook of Dermatology. Oxford: Blackwell Science; 2000: 975-976
    Search in Google Scholar
  • 9 Happle R. Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 2005; 141 (03) 385-388
    CrossrefPubMedSearch in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 16 Ruggieri M, Packer RJ. Why do benign astrocytomas become malignant in NF1?. Neurology 2001; 56 (07) 827-829
    CrossrefPubMedSearch in Google Scholar
  • 17 Ruggieri M, Polizzi A. Choroidal abnormalities and mental retardation in neurofibromatosis type 1. Lancet 2001; 357 (9252): 311-312
    PubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 21 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 29 Ruggieri M, Iannetti P, Clementi M. , et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 32 Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999; 41 (2 Pt 1): 143-164
    CrossrefPubMedSearch in Google Scholar
  • 33 Happle R. Dohi Memorial Lecture. New aspects of cutaneous mosaicism. J Dermatol 2002; 29 (11) 681-692
    CrossrefPubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 35 Pavone P, Nigro F, Falsaperla R. , et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
    CrossrefPubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 37 Pavone P, Praticò AD, Vitaliti G. , et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 41 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 58 Ruggieri M. Familial hypomelanosis of Ito: implications for genetic counselling. Am J Med Genet 2000; 95 (01) 82-84
    CrossrefPubMedSearch in Google Scholar
  • 59 Ruggieri M, Magro G, Ruggieri M, Polizzi A. Tumors and hypomelanosis of Ito. Arch Pathol Lab Med 2001; 125 (05) 599-601
    PubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    PubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 68 Restivo DA, Milone P. Teaching NeuroImages: progressive facial hemiatrophy (Parry-Romberg syndrome) with ipsilateral cerebral hemiatrophy. Neurology 2010; 74 (03) e11
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    Search in Google Scholar
  • 71 Comi A. Current therapeutic options in Sturge-Weber syndrome. Semin Pediatr Neurol 2015; 22 (04) 295-301
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar