Download PDF
Journal of Pediatric Neurology 2018; 16(05): 276-281
DOI: 10.1055/s-0038-1667013
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Cutis Tricolor

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, Italy
,
Agata Polizzi
2   Institute of Neurological Sciences, National Research Council, Catania, Italy
,
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, Italy
3   Maurice Wohl Clinical Neuroscience Institute, King's College London, London, United Kingdom
,
Selene Mantegna
10   Post-graduate School of Pediatrics, Anna Meyer Children's University Hospital, Department of Health Science University of Florence, Florence, Italy
,
Chiara Maria Battaglini
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, Italy
,
Concetta Pirrone
4   Section of Psychology, Department of Educational Sciences University of Catania, Catania, Italy
,
Mario Roggini
5   Department of Pediatrics and Child Neuropsychiatry, Section of Pediatric Radiology, La Sapienza University, Rome, Italy
,
Francesco Lacarrubba
6   Dermatology Clinic, University of Catania, Catania, Italy
,
Giuseppe Micali
6   Dermatology Clinic, University of Catania, Catania, Italy
,
Elena Commodari
4   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
,
Ingo Kennerknecht
8   Institute of Human Genetics, University of Munster, Munster, Germany
,
Carmelo Schepis
9   Unit of Dermatology, Oasi Research Institute-IRCCS, Troina, Enna, Italy
› Author Affiliations
Further Information

Publication History

03 January 2018

11 May 2018

Publication Date:
20 August 2018 (online)

    Permissions and Reprints

Abstract

Cutis tricolor is a skin abnormality consisting in a combination of congenital hyper- and hypopigmented skin lesions (in the form of paired macules, patches, or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon. This phenomenon has been reported so far as a purely cutaneous trait, as a part of a complex malformation phenotype (Ruggieri–Happle syndrome), which includes distinct facial features, cataract, skull and vertebral defects, long bones dysplasia, corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly, and other systemic abnormalities. Cutis tricolor has been also reported as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata) or in association with other skin disturbances (e.g., phacomatosis achromico-melano-marmorata) or in the context of other neurocutaneous phenotypes (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis) or as a sign of complex malformation phenotypes (e.g., microcephaly and dwarfism). More than 20 studies reporting 40 cases are present in the literature with pure cutaneous or syndromic cutis tricolor phenomena and are analyzed in the present study, confirming and expanding the overall phenotype of cutis tricolor. In particular, (1) the skin abnormalities of the cutis tricolor do not evolve over time; (2) there is a typical facial phenotype with long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose, and anteverted nostrils; (3) the skeletal defects are mild-to-moderate and do not progress or cause relevant orthopedic complications; (4) the neurological/behavioral phenotype does not progress and the paroxysmal events (if present) tend to decrease over time; (5) only three patients developed early onset (treatable) cataracts. Different pathologic hypotheses have been postulated, including, early or late postzygotic mutations involving the same gene loci (in the context of the so-called dydymotic theory): such mechanisms can explain the overall skin, bone, lens, and nervous system phenomena of migration of different streaks of clones in the different tissues.

Keywords

cutis tricolor - review - hyperpigmented macules - hypopigmented macules - skeletal anomalies
 

  • References

  • 1 Happle R. Mosaicism in Human Skin. Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin/Heidelberg: Springer-Verlag; 2014
    Google Scholar
  • 2 Happle R, Barbi G, Eckert D, Kennerknecht I. “Cutis tricolor”: congenital hyper- and hypopigmented macules associated with a sporadic multisystem birth defect: an unusual example of twin spotting?. J Med Genet 1997; 34 (08) 676-678
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Khumalo NP, Joss DV, Huson SM, Burge S. Pigmentary anomalies in ataxia--telangiectasia: a clue to diagnosis and an example of twin spotting. Br J Dermatol 2001; 144 (02) 369-371
    CrossrefPubMedGoogle Scholar
  • 5 Baba M, Seçkin D, Akçali C, Happle R. Familial cutis tricolor: a possible example of paradominant inheritance. Eur J Dermatol 2003; 13 (04) 343-345
    PubMedGoogle Scholar
  • 6 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
    CrossrefPubMedGoogle Scholar
  • 7 Seraslan G, Atik E. Cutis tricolor: two case reports. Case Rep Clin Pract Rev 2005; 6: 317-319
    PubMedGoogle Scholar
  • 8 Niessen RC, Jonkman MF, Muis N, Hordijk R, van Essen AJ. Pigmentary mosaicism following the lines of Blaschko in a girl with a double aneuploidy mosaicism: (47,XX,+7/45,X). Am J Med Genet A 2005; 137A (03) 313-322
    CrossrefPubMedGoogle Scholar
  • 9 Larralde M, Happle R. Cutis tricolor parvimaculata: a distinct neurocutaneous syndrome?. Dermatology 2005; 211 (02) 149-151
    CrossrefPubMedGoogle Scholar
  • 10 Boente MC, Obeid R, Asial RA, Bibas-Bonet H, Coronel AM, Happle R. Cutis tricolor coexistent with cutis marmorata telangiectatica congenita: “phacomatosis achromico-melano-marmorata”. Eur J Dermatol 2008; 18 (04) 394-396
    PubMedGoogle Scholar
  • 11 Ruggieri M, Roggini M, Kennerknecht I, Schepis C, Iannetti P. Cutis tricolor (Ruggieri-Happle syndrome). In: Ruggieri M, Pascual-Castroviejo I, Di Rocco C. , eds. Neurocutaneous Disorders. Phakomatoses & Hamartoneoplastic Syndromes. Wien/New York: Springer-Verlag; 2008: 461-471
    Google Scholar
  • 12 Ruggieri M, Iannetti F, Polizzi A. , et al. Cataracts in three children with a newly recognised neurocutaneous malformation phenotype with “cutis tricolor”. Br J Ophthalmol 2009; 93 (01) 127-128
    CrossrefPubMedGoogle Scholar
  • 13 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 Boente MdelC, Bazan C, Montanari D. Cutis tricolor parvimaculata in two patients with ring chromosome 15 syndrome. Pediatr Dermatol 2011; 28 (06) 670-673
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Oiso N, Matsuda H, Kawada A. Cutis tricolor of pure cutaneous trait as leukoderma and nevus spilus. J Dermatol 2013; 40 (06) 490-491
    CrossrefPubMedGoogle Scholar
  • 18 Torchia D, Schachner LA, Izakovic J. Cutis tricolor. Cutis 2013; 91 (01) 11-16
    PubMedGoogle Scholar
  • 19 Tekin B, Yucelten AD, Bayri Y. A novel association of an uncommon pigmentation pattern: coexistence of cutis tricolor with intracranial teratoma and holoprosencephaly. Dermatol Online J 2014; 20 (10) 10
    PubMedGoogle Scholar
  • 20 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
    CrossrefPubMedGoogle Scholar
  • 21 Ruggieri M. Familial hypomelanosis of ito: implications for genetic counselling. Am J Med Genet 2000; 95 (01) 82-84
    CrossrefPubMedGoogle Scholar
  • 22 Ruggieri M, Magro G, Ruggieri M, Polizzi A. Tumors and hypomelanosis of Ito. Arch Pathol Lab Med 2001; 125 (05) 599-601
    PubMedGoogle Scholar
  • 23 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
    PubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 POSSUM - Pictures of Standard Syndromes and Undiagnosed Malformations. Melbourne: Murdoch Children Research Institute, 2016 [POSSUM web]. Available at: https://www.possum.net.au . Accessed December 23, 2017
    PubMed
  • 26 Happle R. Didymotic skin disorders. In: Happle R. , ed. Mosaicism in Human Skin. Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin/Heidelberg: Springer-Verlag; 2014: 109-114
    Google Scholar
  • 27 Ruggieri M, Praticò AD. Mosaic neurocutaneous disorders and their causes. Semin Pediatr Neurol 2015; 22 (04) 207-233
    CrossrefPubMedGoogle Scholar
  • 28 Jinnette VA, Courter AM, Lowry JW, Buckley NH, White KT, Hoegerman SF. Mechanisms of twin spotting. Lancet 1990; 336 (8706): 61
    CrossrefPubMedGoogle Scholar
  • 29 Koopman RJ. Concept of twin spotting. Am J Med Genet 1999; 85 (04) 355-358
    CrossrefPubMedGoogle Scholar
  • 30 Happle R. The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet A 2016; 170A (02) 452-459
    PubMedGoogle Scholar
  • 31 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
    CrossrefPubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 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
    CrossrefPubMedGoogle Scholar
  • 34 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
    CrossrefPubMedGoogle Scholar
  • 35 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
    CrossrefPubMedGoogle Scholar
  • 36 Ruggieri M, Packer RJ. Why do benign astrocytomas become malignant in NF1?. Neurology 2001; 56 (07) 827-829
    CrossrefPubMedGoogle Scholar
  • 37 Ruggieri M, Polizzi A. Choroidal abnormalities and mental retardation in neurofibromatosis type 1. Lancet 2001; 357 (9252): 311-312
    PubMedGoogle Scholar
  • 38 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
    CrossrefPubMedGoogle Scholar
  • 39 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
    CrossrefPubMedGoogle Scholar
  • 40 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
    CrossrefPubMedGoogle Scholar
  • 41 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
    CrossrefPubMedGoogle Scholar
  • 42 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
    CrossrefPubMedGoogle Scholar
  • 43 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
    CrossrefPubMedGoogle Scholar
  • 44 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
    CrossrefPubMedGoogle Scholar
  • 45 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
    CrossrefPubMedGoogle Scholar
  • 46 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
    CrossrefPubMedGoogle Scholar
  • 47 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
    PubMedGoogle Scholar
  • 48 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
    CrossrefPubMedGoogle Scholar
  • 49 Ruggieri M, Iannetti P, Clementi M. , et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
    CrossrefPubMedGoogle Scholar
  • 50 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
    CrossrefPubMedGoogle Scholar
  • 51 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
    CrossrefPubMedGoogle Scholar
  • 52 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
    CrossrefPubMedGoogle Scholar
  • 53 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
    CrossrefPubMedGoogle Scholar
  • 54 Happle R. Mosaicism in human skin. Understanding the patterns and mechanisms. Arch Dermatol 1993; 129 (11) 1460-1470
    CrossrefPubMedGoogle Scholar
  • 55 Happle R. Pigmentary patterns associated with human mosaicism: a proposed classification. Eur J Dermatol 1993; 3: 170-174
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 57 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
    CrossrefPubMedGoogle Scholar
  • 58 Taybi H, Lachman RS. Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasia. 4th ed. St. Louis: Mosby; 1996
    Google Scholar
  • 59 Ruggieri M, Pavone V, Polizzi A. , et al. Tuberculosis of the ankle in childhood: clinical, roentgenographic and computed tomography findings. Clin Pediatr (Phila) 1997; 36 (09) 529-534
    CrossrefPubMedGoogle Scholar
  • 60 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
    CrossrefPubMedGoogle Scholar
  • 61 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
    CrossrefPubMedGoogle Scholar
  • 62 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
    CrossrefPubMedGoogle Scholar
  • 63 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
    PubMedGoogle Scholar
  • 64 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
    CrossrefPubMedGoogle Scholar
  • 65 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 67 Pavone P, Nigro F, Falsaperla R. , et al. Hemihydranencephaly: living with half brain dysfunction. Ital J Pediatr 2013; 39: 3
    CrossrefPubMedGoogle Scholar
  • 68 Pavone P, Praticò AD, Vitaliti G. , et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
    CrossrefPubMedGoogle Scholar
  • 69 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
    PubMedGoogle Scholar
  • 70 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
    CrossrefPubMedGoogle Scholar
  • 71 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langerhans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
    CrossrefPubMedGoogle Scholar