Neurological manifestations in individuals with pure cutaneous or syndromic (Ruggieri-Happle syndrome) phenotypes with "cutis tricolor": a study of 14 cases

• Published in: Neuropediatrics Vol. 41; no. 2; p. 60
• Main Authors: Lionetti, E, Pavone, P, Kennerknecht, I, Failla, G, Schepis, C, De Pasquale, R, Pavone, L, Ruggieri, M
• Format: Journal Article
• Language: English
• Published: Germany 01-08-2010
• Subjects: Adolescent; Adult; Brain - pathology; Child; Child, Preschool; Chondrodysplasia Punctata - complications; Chondrodysplasia Punctata - pathology; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Male; Nervous System Diseases - etiology; Neurologic Examination - methods; Neuropsychological Tests; Phenotype; Pigmentation Disorders - complications; Pigmentation Disorders - pathology; Retrospective Studies; Skin - pathology; Young Adult
• ISSN: 1439-1899
• DOI: 10.1055/s-0030-1261919

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.
The aim of this study was to define the spectrum of neurological abnormalities in cutis tricolor.
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.
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).
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.