Cutis Tricolor (Ruggieri-Happle Syndrome)

Cutis tricolor: a literature review and report of five new cases

“…This phenomenon has been reported so far either (18): (I) as an purely cutaneous trait (3,5,7,11,17,18); (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) (18,(21)(22)(23) including distinct facial (a peculiar facial phenotype consisting in coarse, asymmetric and later in adolescence elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils, low-set ears, large phyltrum), eye (congenital cataract), skeletal (small skull, dystrophic vertebrae, and mildly bowed long bones), nervous system [corpus callosum anomalies, white matter abnormalities (i.e., delayed myelination), holoprosencephaly and cerebellar anomalies] and systemic abnormalities (2,3,6,8,(11)(12)(13)(14)16,18,19); (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata) (9,15,18) [different from the autosomal dominant congenital hypo-and hyperpigmented macules (Westerhof syndrome; MIM # 154000)]; and (IV) in association with other skin disturbances [e.g., cutis marmorata telangectasica congenita (phacomatosis achromico-melano-marmorata)] or in the context of other skin disorders (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or neurocutaneous phenotypes (4,10,13,20).…”

“…The existing literature revealed 19 previous studies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) for a total number of 35 cases with purely cutaneous traits (3,5,7,11,17,18) and with a combination of paired skin phenomena of the cutis tricolor type and associated cutaneous/ systemic/neurological manifestations (2)(3)(4)6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

“…Pure cutaneous traits (3,5,7,11,17) and variant forms have been also reported (9,15) and the skin anomaly has been recorded within the context of well-known and less well-known phenotypes (4,10,20).…”

“…The term cutis tricolor describes the combination of congenital hyper-and hypopigmented lesions (in the form of macules, patches or streaks), in close proximity to each other, in a background of normal skin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). This phenomenon has been reported so far either (18): (I) as an purely cutaneous trait (3,5,7,11,17,18); (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) (18,(21)(22)(23) including distinct facial (a peculiar facial phenotype consisting in coarse, asymmetric and later in adolescence elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils, low-set ears, large phyltrum), eye (congenital cataract), skeletal (small skull, dystrophic vertebrae, and mildly bowed long bones), nervous system [corpus callosum anomalies, white matter abnormalities (i.e., delayed myelination), holoprosencephaly and cerebellar anomalies] and systemic abnormalities (2,3,6,8,(11)(12)(13)(14)16,18,19); (III) as a distinct type with mult...…”

“…Ruggieri (3) subsequently expanded the cutaneous phenotype by including cases with abnormal paired pigmentation in the form of large patches (in the form of a yet unclassified archetypical pattern of cutaneous mosaicism) (1,23,(26)(27)(28) or streaks (sash-like pattern of cutaneous mosaicism) (1,23) diffusely involving the body associated (case 2) (3) or not (case 1) (3) to systemic defects. The spectrum of extracutaneous manifestations further expanded in recent years including specific facial dysmorphic, skeletal and brain abnormalities (6,(11)(12)(13)(14)16,19).…”