A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features

Pavone, Piero; Praticò, Andrea D.; Gentile, Giulia; Falsaperla, Raffaele; Iemmolo, Rosario; Guarnaccia, Maria; Cavallaro, Sebastiano; Ruggieri, Martino

doi:10.1016/j.ejmg.2016.03.002

Cited by 39 publications

(53 citation statements)

References 29 publications

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“…By literature review (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and personal experience ( Tables 1,2) we have recorded 40 cases so far with the following demographic, clinical, laboratory and imaging features and natural history.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Literature Reviewmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 98%

“…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...…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Ruggieri

Polizzi

Schepis

et al. 2016

Quant. Imaging Med. Surg.

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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

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Section: Discussionmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Ruggieri

Polizzi

Schepis

et al. 2016

Quant. Imaging Med. Surg.

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Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

Wang

Guo

2017

Brain and Development

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Megalencephaly Capillary Malformation Syndrome

Praticò

Polizzi²,

Salafia³

et al. 2018

J Pediatr Neurol

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Megalencephaly capillary malformation polymicrogyria (MCAP) syndrome is characterized by the sporadic occurrence of congenital and progressive megalencephaly, brain malformations including polymicrogyria, pre- and postnatal overgrowth with body asymmetry, cutaneous vascular malformations (including capillary malformation and cutis marmorata), digital anomalies connective tissue dysplasia (including skin and joint laxity), and developmental delay. In the past 10 years, the specific cause of the disease has been found in gain-of-function mutations of PIK3CA gene, mostly somatic/postzygotic but in rare cases also de novo germline. Such gene encodes for PI3K, a critical member of the PI3K-AKT-mTOR pathway: genetic changes lead to an over-activation of this signaling system, with increased vascular, limb, and brain cell development, progression, and survival. Interestingly, mutations in the same gene can cause other clinically heterogeneous syndromes, including CLOVE syndrome, macrodactyly, focal adipose overgrowth, epidermal nevi, facial infiltrating lipomatosis: all these syndromes (even if heterogeneous) are now considered a unique spectrum, known as PIK3CA-related overgrowth syndrome. On the contrary, a disease strictly similar to MCAP, characterized by megalencephaly, polymicrogyria, polydactyly, and hydrocephalus has been found to be caused by mutations in two other PI3K-AKT-mTOR-releted genes, AKT3 and PIK3R2, and for this reason is not included in the upper mentioned group of syndromes. With the exception of neurosurgery strategies for hydrocephalus and posterior fossa overcrowding, therapeutic options are nowadays limited, even if gene-targeted treatment protocols have been proposed and protocols with such agents (i.e., Arq092) are currently ongoing in small groups of patients with promising results.

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A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features

Cited by 39 publications

References 29 publications

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

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

Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

Megalencephaly Capillary Malformation Syndrome

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