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

Quant. Imaging Med. Surg.

Polizzi

Schepis

et al. 2016

Background: Cutis tricolor is a skin abnormality consisting in a combination of congenital hyper-and hypopigmented skin lesions (in the form of paired macules, patches or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon and today is clear that not all cases of cutis tricolor represent one single entity. This phenomenon has been reported so far either: (I) as an purely cutaneous trait; (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) including distinct facial features, eye (cataract), skeletal (skull and vertebral defects, and long bones dysplasia), nervous system (corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly) and systemic abnormalities; (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata); 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 (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or complex malformation phenotypes (e.g., microcephaly and dwarfism).Methods: (I) Review of the existing literature; and (II) information on our personal experience (clinical, laboratory and imaging data) on new cases with cutis tricolor seen and followed-up at our institutions during years 2010-2016. Results:The existing literature revealed 19 previous studies (35 cases) with pure cutaneous or syndromic cutis tricolor phenomena. Our personal experience included 5 unpublished patients (3 boys; 2 girls; currently aged 2 to 14 years) seen and followed-up at our Institutions in Italy who had: (I) skin manifestations of the cutis tricolor type (N=5); (II) skeletal abnormalities including small skull (n=2), obtuse angle of mandible (n=3), mild to moderate scoliosis (n=3), vertebral defects (n=3), and long bones bowing (n=3); mild psychomotor delay (n=3); epilepsy (n=2); anomalies of the corpus callosum (n=3); and cavum vergae (n =2).Conclusions: This study further confirms and expands the overall phenotype of cutis tricolor. By literature review and personal experience we conclude that the skin abnormalities of the cutis tricolor type are stable over time; the skeletal defects are mild to moderate and do not progress or cause relevant orthopaedic complications; the neurological/behavioural phenotype does not progress and the paroxysmal events (when present) tend to decrease over time; there is a typical facial phenotype in some patients (long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted

Section: Patientsmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Quant. Imaging Med. Surg.

Polizzi

Schepis

et al. 2016

Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke–Davidoff–Masson type in two patients

American J of Med Genetics Pt A

Milone

Pavone

et al. 2012

The term twin spotting refers to phenotypes characterized by the spatial and temporal co-occurrence of two (or more) different nevi arranged in variable cutaneous patterns, and can be associated with extra-cutaneous anomalies. Several examples of twin spotting have been described in humans including nevus vascularis mixtus, cutis tricolor, lesions of overgrowth, and deficient growth in Proteus and Elattoproteus syndromes, epidermolytic hyperkeratosis of Brocq, and the so-called phacomatoses pigmentovascularis and pigmentokeratotica. We report on a 28-year-old man and a 15-year-old girl, who presented with a previously unrecognized association of paired cutaneous vascular nevi of the telangiectaticus and anemicus types (naevus vascularis mixtus) distributed in a mosaic pattern on the face (in both patients) and over the entire body (in the man) and a complex brain malformation (in both patients) consisting of cerebral hemiatrophy, hypoplasia of the cerebral vessels and homolateral hypertrophy of the skull and sinuses (known as Dyke-Davidoff-Masson malformation). Both patients had facial asymmetry and the young man had facial dysmorphism, seizures with EEG anomalies, hemiplegia, insulin-dependent diabetes mellitus (IDDM), autoimmune thyroiditis, a large hepatic cavernous vascular malformation, and left Legg-Calvé-Perthes disease (LCPD) [LCPD-like presentation]. Array-CGH analysis and mutation analysis of the RASA1 gene were normal in both patients.

Klippel‐Trenaunay syndromein a boy with concomitant ipsilateral overgrowth and undergrowth

American J of Med Genetics Pt A

Pavone

Polizzi

et al. 2014

Klippel-Trenaunay syndrome comprises congenital vascular malformations of the capillary (nevus flammeus), venous (varicosities) or lymphatic systems and disturbed (usually over-) growth of one or more extremities and adjacent parts of the trunk. In some individuals the affected body area may show reduced rather than increased growth. Such patients have been described inverse Klippel-Trenaunay syndrome and included within the spectrum of the syndrome. We report on a 3-year-old boy with vascular malformation of the nevus flammeus type extending from the right buttock to the sole of the right foot with clinical and radiological evidence of leg varicosities and underlying deficiency of the soft tissues and bone. In addition, he had macrodactyly of the first, second, and third toes with small nails, and cutaneous syndactyly of the second and third toes of the ipsilateral foot. Cranial magnetic resonance imaging showed high signal lesions in the peritrigonal areas with normal spinal images. This mosaic phenotype demonstrates that decreased and increased growth can coexist in the same body area of an individual with Klippel-Trenaunay syndrome.