Neurological Manifestations in Individuals with Pure Cutaneous or Syndromic (Ruggieri-Happle Syndrome) Phenotypes with “Cutis Tricolor”: A Study of 14 Cases

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

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