Hepatoblastoma and heart transplantation in a patient with cardio‐facio‐cutaneous syndrome

Al-Rahawan, Mohamad M.; Chute, Deborah J.; Sol‐Church, Katia; Gripp, Karen W.; Stabley, Deborah L.; McDaniel, Nancy L.; Wilson, William G.; Waldron, Peter

doi:10.1002/ajmg.a.31819

Cited by 45 publications

(34 citation statements)

References 19 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 None of our patients showed malignancy, and only a single patient with MEK1 mutation (Y130C) has been reported with a hepatoblastoma. 25 Consistent with this finding, no somatic mutation in MEK1 gene has been observed in hepatoblastoma or in any other solid tumors (http:// www.sanger.ac.uk/genetics/CGP/cosmic/). Similarly, the somatically acquired V600E amino acid substitution of BRAF occurs at high frequency in cancer, but it has not been observed among patients with CFCS.…”

Section: Discussionsupporting

confidence: 59%

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

et al. 2009

View full text Add to dashboard Cite

Cardio-facio-cutaneous syndrome (CFCS) is a rare disease characterized by mental retardation, facial dysmorphisms, ectodermal abnormalities, heart defects and developmental delay. CFCS is genetically heterogeneous and mutations in the KRAS, BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2) genes, encoding for components of the RAS-mitogen activated protein kinase (MAPK) signaling pathway, have been identified in up to 90% of cases. Here we screened a cohort of 33 individuals with CFCS for MEK1 and MEK2 gene mutations to further explore their molecular spectrum in this disorder, and to analyze genotypephenotype correlations. Three MEK1 and two MEK2 mutations were detected in six patients. Two missense MEK1 (L42F and Y130H) changes and one in-frame MEK2 (K63_E66del) deletion had not been reported earlier. All mutations were localized within exon 2 or 3. Together with the available records, the present data document that MEK1 mutations are relatively more frequent than those in MEK2, with exons 2 and 3 being mutational hot spots in both genes. Mutational analysis of the affected MEK1 and MEK2 exons did not reveal occurrence of mutations among 75 patients with Noonan syndrome, confirming the low prevalence of MEK gene defects in this disorder. Clinical review of known individuals with MEK1/MEK2 mutations suggests that these patients show dysmorphic features, ectodermal abnormalities and cognitive deficit similar to what was observed in BRAF-mutated patients and in the general CFCS population. Conversely, congenital heart defects, particularly mitral valve and septal defects, and ocular anomalies seem to be less frequent among MEK1/MEK2 mutation-positive patients.

show abstract

Section: Discussionsupporting

confidence: 59%

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

et al. 2009

View full text Add to dashboard Cite

show abstract

“…One individual with CFC (BRAF mutation) had a hepatoblastoma, possibly the result of postcardiac transplant immunosuppression. 34 Additional studies are needed to accurately assess the risk of malignancy in CFC. 74 …”

Section: Hematology/oncology Conditionsmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

“…2,18 A CFC patient with a MEK1 mutation has been reported to have developed hepatoblastoma after cardiac transplantation. 19 To date, 104 CFC patients with BRAF mutations and 42 with CFC patients with MEK1/2 mutations have been reported. 15 The frequency of the association with malignant tumors cannot be neglected.…”

Section: Discussionmentioning

confidence: 99%

Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome

Ohtake

Aoki²,

Saito³

et al. 2011

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by a distinctive facial appearance, ectodermal abnormalities, and heart defects. Clinically, it overlaps with both Noonan syndrome and Costello syndrome. Mutations in KRAS, BRAF, and MAP2K1/2 (MEK1/2) have been identified in patients with CFC syndrome. BRAF mutations are involved in more than 80% of CFC syndrome patients, and we have reported earlier that 2 CFC patients with BRAF mutations developed acute lymphoblastic leukemia. Here we report a boy with CFC syndrome who developed non-Hodgkin lymphoma. At 2 months of age, he developed pneumonia with pleurisy and was diagnosed as having non-Hodgkin lymphoma (precursor T-cell lymphoblastic lymphoma) by cytopathologic examination of the pleural fluid. He was suspected of having Noonan syndrome because of his facial appearance, webbed neck, and cubitus valgus. Precursor T-cell lymphoblastic lymphoma was treated by the TCCSG NHL 94-04 protocol. At 9 years of age, he was clinically reevaluated and diagnosed as having CFC syndrome because of his distinctive facial appearance, multiple nevi, and moderate mental retardation. Sequencing analysis showed a germline p.A246P (c.736G>C) mutation in BRAF reported earlier in CFC syndrome. Molecular diagnosis and careful observation should be considered in children with CFC syndrome.

show abstract

Hepatoblastoma and heart transplantation in a patient with cardio‐facio‐cutaneous syndrome

Cited by 45 publications

References 19 publications

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

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

Non-Hodgkin Lymphoma in a Patient With Cardiofaciocutaneous Syndrome

Contact Info

Product

Resources

About