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DOI: 10.1055/s-0030-1261919
© Georg Thieme Verlag KG Stuttgart · New York
Neurological Manifestations in Individuals with Pure Cutaneous or Syndromic (Ruggieri-Happle Syndrome) Phenotypes with “Cutis Tricolor”: A Study of 14 Cases
Publikationsverlauf
received 12.03.2010
accepted 15.06.2010
Publikationsdatum:
26. August 2010 (online)
![](https://www.thieme-connect.de/media/neuropediatrics/201002/lookinside/thumbnails/10.1055-s-0030-1261919-1.jpg)
Abstract
Background: The term cutis tricolor describes the combination of congenital hyper- and hypo-pigmented skin lesions in close proximity to each other in a background of normal complexion. This phenomenon has been reported so far: (i) as pure cutaneous trait, (ii) as a part of a complex malformation syndrome (Ruggieri-Happle syndrome – RHS), (iii) as a distinct type (cutis tricolor parvimaculata); (iv) in association with other (e. g., vascular) skin disturbances.
Aim: The aim of this study was to define the spectrum of neurological abnormalities in cutis tricolor.
Methods: A retrospective and prospective 14-year study of clinical, electroencephalographic (EEG), neuroradiological (MRI), cytogenetic and ZFHX1B gene studies of 14 individuals (8 M, 6 F; aged 2–28 years) with cutis tricolor (4 pure cutaneous; 10 syndromic) was undertaken.
Results: Neurological involvement was recorded in 71.4% (10/14) of the patients [100% (10/10) in RHS and null (0/4) in cases with isolated skin manifestations] and included psychomotor delay (n=8), seizures (n=9), EEG abnormalities (n=6), a behavioural phenotype (n=4), non-specific brain abnormalities (n=6). Genetic analyses excluded ZFHX1B mutations and revealed a 19qter deletion (n=1).
Conclusions: Even though we could not exclude the ascertainment and referral biases, we concluded that cutis tricolor may be a marker of underlying neurological involvement particularly in subjects with a syndromic (RHS) phenotype.
Key words
cutis tricolor - neurology - Ruggieri-Happle syndrome
References
- 1 Baba M, Seckin D, Akcali C. et al . Familial cutis tricolor: a possible example of paradominant inheritance. Eur J Dermatol. 2003; 13 343-345
- 2 Battaglia A, Gurrieri F, Bertini E. et al . The inv dup (15) syndrome: a clinically recognizable syndrome with altered behaviour, mental retardation, and epilepsy. Neurology. 1997; 48 1081-1086
- 3 Boente M del C, Obeid R, Asial RA. et al . Cutis tricolor coexistent with cutis marmorata telangiectatica congenita: “phacomatosis achromico-melano-marmorata”. Eur J Dermatol. 2008; 18 394-396
- 4 De las Heras E, Boixeda JP, Lader A. et al . Paired melanotic and achromic macules in a case of phacomatosis pigmentovascularis: A further example of twin spotting?. Am J Med Genet. 1997; 70 336-337
- 5 Happle R. Mosaicism in human skin. Understanding the patterns and mechanisms. Arch Dermatol. 1993; 129 1460-1470
- 6 Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol. 1999; 41 143-161
- 7 Happle R, Barbi G, Eckert D. et al . “Cutis tricolor”: congenital hyper- and hypopigmented macules associated with a sporadic multisystem birth defect: an unusual example of twin spotting?. J Med Genet. 1997; 34 676-678
- 8 Khumalo NP, Joss DV, Huson SM. et al . Pigmentary anomalies in ataxia-telangiectasia: a clue to diagnosis and an example of twin spotting. Br J Dermatol. 2001; 1444 369-371
- 9 Koopman RJJ. Concept of twin spotting. Am J Med Genet. 1999; 85 355-358
- 10 Larralde M, Happle R. Cutis tricolor parvimaculata: a distinct neurocutaneous phenotype?. Dermatology. 2005; 211 149-151
- 11 Lezak MD. Neuropsychological Assessment. 3rdedn. New York: Oxford University Press; 1995
- 12 Mowat DR, Wilson MJ, Goosens M. Mowat-Wilson syndrome. J Med Genet. 2003; 40 305-310
- 13 O’Brien G, Yule W. Behavioural Phenotypes. London: Cambridge University Press; 1995
- 14 POSSUM [Possum-web]. Pictures of Standard Syndromes and Undiagnosed Malformations . Version 7.0. Melbourne: Murdoch Institute for Research into Birth Defects & Murdoch Children Research Institute, ©. 2007–2010 available at http://www.possum.net.au
- 15 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; 159 745-749
- 16 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognised neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet. 2003; 120 110-116
- 17 Ruggieri M, Roggini M, Kennerknecht I. et al .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
- 18 Ruggieri M, Pascual-Castroviejo I, Di Rocco C. Neurocutaneous Disorders. Phakomatoses & Hamartoneoplastic Syndromes. Wien/New York: Springer-Verlag; 2008
- 19 Ruggieri M, Iannetti F, Polizzi A. et al . Cataracts in 3 children with a newly recognised neurocutaneous malformation phenotype with “cutis tricolour”. Br J Ophthalmol. 2009; 93 127-128
- 20 Seraslan G, Atik E. Cutis tricolor: 2 case reports. Case Rep Clin Pract Rev. 2005; 6 317-319
- 21 Vélez A, Salido R, Amorrich-Campos V. et al . Hereditary congenital hypopigmented and hyperpigmented macules (Westerhof syndrome) in 2 siblings. Br J Dermatol. 2009; 161 1399-1400
- 22 Westerhof W, Beemer FA, Cormane RH. et al . Hereditary congenital hypopigmented and hypopigmented macules. Arch Dermatol. 1978; 114 931-936
- 23 Wilson M, Mowat D, Dastot-Le Moal F. et al . Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. Am J Med Genet A. 2003; 119 257-265
- 24 Winter RM, Baraitser M. The London Dysmorphology Database [version 1.0.19 to 1.0.20]. Oxford: Oxford University Press, ©; 2008. available at http://www.Imdatabases.com
- 25 Zweier C, Horn D, Kraus C. et al . Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype. Am J Med Genet. 2006; 140 869-872
Correspondence
Martino RuggieriMD, PhD
Department of Formative
Processes
University of Catania
Via Biblioteca 4 [Palazzo Ingrassia]
95124 Catania
Italy
Telefon: +39/095/746 6301
Fax: +39/095/316 792
eMail: m.ruggieri@unict.it