Spectrum of skeletal abnormalities in a complex malformation syndrome with “cutis tricolor” (Ruggieri‐Happle syndrome)

AbstractBackground:  The term cutis tricolor describes the combination of congenital hyper‐ and hypopigmented skin lesions in close proximity to each other in a background of normal complexion. This phenomenon has been reported: (i) as a purely 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.Objectives:  To delineate the spectrum of skeletal defects in cutis tricolor.Methods:  Retrospective and prospective analysis of skeletal surveys in 14 subjects (eight men; six women; aged 2–28 years) with cutis tricolor [4 purely cutaneous trait; 10 syndromic (RHS)].Results:  Bone abnormalities were recorded in 71.4% (10/14) of patients [100% (10/10) of cases with (other‐than‐skeletal) extra‐cutaneous manifestations vs. null (0/4) in cases with purely cutaneous traits] and included overall small skull (n = 6); prognathism (n = 6); ‘J’‐shaped pituitary fossa (n = 1); absence of atlas posterior arch (n = 3); frontal bossing (n = 6); scoliosis (n = 9) with kyphosis (n = 6) and/or lordosis (n = 6); vertebral (n = 9) and ribs (n = 4) defects. Negative ZFHX1B gene analyses excluded overlaps with Mowat–Wilson syndrome.Conclusions:  Cutis tricolor may be a marker of underlying skeletal involvement particularly in subjects with a complex syndromic (RHS) phenotype.