Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome

Siegel, Dawn H.; McKenzie, J.; Frieden, Ilona J.

doi:10.1111/j.1365-2133.2010.10122.x

Cited by 62 publications

(99 citation statements)

References 34 publications

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“…One statistically significant genotypephenotype correlation is the incidence of pulmonic stenosis, which is present in 50% of individuals with CFC with a BRAF gene mutation and 37% of those with a MEK gene mutation. 15 It also appears that, while not statistically significant, MEK mutations may be associated with a higher likelihood of prematurity, ventricular septal defects, pectus deformity, urogenital abnormalities, and dermatological abnormalities, 15,16 whereas BRAF mutations may be more commonly associated with hypertrophic cardiomyopathy (HCM), atrial septal defects, moderate to severe intellectual disability, and significant feeding difficulties. 15 Among the RASopathies as a whole, there are relatively well-established genotypephenotype correlations with respect to cognitive development.…”

Section: Genotype/phenotype Correlationsmentioning

confidence: 99%

“…3,[31][32][33] Sparse, curly, and friable hair, with sparse or absent eyebrows with hyperkeratosis (ulerythema ophryogenes) are very common in CFC and occur with greater frequency than in other RASopathies. 3,16,32 Ocular features include ptosis, hypertelorism, downslanting palpebral fissures, and epicanthal folds. The nose is often short with a broad nasal base, bulbous tip, and anteverted nares.…”

Section: Clinical Description With Differential Diagnosismentioning

confidence: 99%

“…36 Although the severity and type of ectodermal involvement varies (Table 3), virtually all CFC individuals develop some form of cutaneous involvement and for this reason, dermatologic consultation and follow-up are recommended. 16,22,38 Among the manifestations are wavy or curly scalp hair, with sparse hair at the temples, poor hair growth, and sparse arm and leg hair. Ulerythema ophryogenes, characterized by brow erythema with loss of follicles, causes sparse or absent eyebrows with only 10% of individuals having normal eyebrows.…”

Section: Dermatologic Manifestationsmentioning

confidence: 99%

“…Ulerythema ophryogenes, characterized by brow erythema with loss of follicles, causes sparse or absent eyebrows with only 10% of individuals having normal eyebrows. 16 Numerous acquired melanocytic nevi are striking features of CFC, with this finding less common in other RASopathies. 39 It is not uncommon for individuals to develop over 100 nevi as they age, with the nevi not restricted to light-exposed areas.…”

Section: Dermatologic Manifestationsmentioning

confidence: 99%

“…39 It is not uncommon for individuals to develop over 100 nevi as they age, with the nevi not restricted to light-exposed areas. 16 To date, there are no reports of malignant transformation of pigmented lesions in CFC.…”

Section: Dermatologic Manifestationsmentioning

confidence: 99%

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Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

et al. 2014

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Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

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Section: Genotype/phenotype Correlationsmentioning

confidence: 99%

Section: Clinical Description With Differential Diagnosismentioning

confidence: 99%

Section: Dermatologic Manifestationsmentioning

confidence: 99%

Section: Dermatologic Manifestationsmentioning

confidence: 99%

Section: Dermatologic Manifestationsmentioning

confidence: 99%

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Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

et al. 2014

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Cutaneous Toxic Effects Associated With Vemurafenib and Inhibition of the BRAF Pathway

Huang¹,

Hepper²,

Anadkat³

et al. 2012

Arch Dermatol

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Background: The development of a novel BRAF inhibitor, vemurafenib, has been associated with impressive tumor regression in patients with BRAF-positive stage IV melanoma. In the phase 3 clinical trials, dermatologic toxic effects associated with vemurafenib were described, namely, the development of eruptive squamous cell carcinomas. Herein, 3 cases are presented that highlight the development of squamous cell carcinomas and other cutaneous sequelae that have not been previously reported and are reminiscent of those observed with administration of the multikinase inhibitor sorafenib tosylate. In addition, the current understanding of the molecular mechanisms underlying these toxic effects is reviewed. Observations: The development of keratosis pilarislike eruptions; seborrheic dermatitis-like rashes; and hy-perkeratotic, tender plantar papules reminiscent of those seen in sorafenib-associated hand-foot skin reaction, as well as squamous cell carcinomas, is presented in association with vemurafenib-based treatment of metastatic melanoma. Conclusions: The development of sorafenib-like cutaneous sequelae (squamous cell carcinomas, keratosis pilaris-like eruptions, seborrheic dermatitis-like rashes, and hand-foot skin reaction) associated with vemurafenib administration suggests that BRAF inhibition alone may be sufficient to induce these changes.

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Multiple café au lait spots in familial patients with MAP2K2 mutation

Tamura

Shimizu

Torii

et al. 2013

American J of Med Genetics Pt A

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Recent advances in genetic diagnostic technologies have made the classic disease nosology highly complicated. This situation is exemplified by rasopathies, among which neurofibromatosis type 1 and Noonan syndrome represent prototypic entities. The former condition is characterized by multiple café au lait spots and neurofibromas, while the latter is characterized by distinct facial features, webbed neck, congenital heart disease, and a short stature. On rare occasions, the features of both neurofibromatosis and Noonan syndrome co-exist within an individual; such patients are diagnosed as having neurofibromatosis-Noonan syndrome. Here, we report familial patients with multiple café au lait spots and Noonan syndrome-like facial features. A mutation analysis unexpectedly revealed a mutation in MAP2K2 in both the propositus and his mother. The propositus fulfilled the diagnostic criteria for neurofibromatosis type 1, but his mother did not. Their phenotype was not consistent with that of cardio-facio-cutaneous syndrome, which is classically known to be associated with MAP2K2 mutations. The mother of the propositus had cervical cancer at the age of 23 years, consistent with the oncogenic tendency associated with rasopathies. The phenotypic combination of multiple café au lait spots and Noonan syndrome-like facial features suggested a diagnosis of neurofibromatosis-Noonan syndrome. Whether this condition represents a discrete disease entity or a variable expression of neurofibromatosis type 1 has long been debated. The present observation suggests that some perturbation in the RAS/MAPK signaling cascade results in multiple café au lait spots, a key diagnostic phenotype of rasopathies, although the exact mechanism remains to be elucidated.

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Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome

Cited by 62 publications

References 34 publications

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

Cutaneous Toxic Effects Associated With Vemurafenib and Inhibition of the BRAF Pathway

Multiple café au lait spots in familial patients with MAP2K2 mutation

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