Advances in diagnosis and treatment of cardio-facio-cutaneous syndrome in children / 国际儿科学杂志

Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic syndrome associated with abnormal activation of RAS-mitogen-activated protein kinase(RAS-MAPK)signal transduction pathway.Causative genes are BRAF, MAP2K1, MAP2K2 and KRAS.CFCS is an autosomal dominant disorder characterized by dysmorphic craniofacial features, congenital heart disease, dermatologic abnormalities, gastrointestinal dysfunction, failure to thrive, neurocognitive delay and epilepsy, whose phenotype overlaps with many other RASopathies.Final diagnosis of CFCS can be reached by classical presentation and genetic testing.Early diagnosis helps to evaluate risk of severe complications of specific genotype and improve prognosis of CFCS patients.At present, there is no effective treatment of CFCS although inhibitors of MEK may improve partial phenotype of CFCS animal models.Once diagnosed with CFCS, the patients need multidisciplinary assessment and treatment.

Eritema multiforme, una rara presentación de exantema en población pediátrica: a propósito de un caso / Erythema multiforme, a rare occurrence of exanthema in the pediatric population: on the subject of a case

El Eritema multiforme (EM) o eritema polimorfo es una enfermedad aguda de la piel de naturaleza inmunológica con o sin compromiso de mucosas, que puede comportarse como crónica recurrente. Se presenta con lesiones cutáneas en diana distintivas, a menudo acompañado de úlceras o bullas en mucosas (oral, genital u ocular). Entre sus formas clínicas se distingue: una forma menor caracterizado por un síndrome cutáneo leve y su forma mayor que se manifiesta como una afectación cutánea con daño mucoso marcado. Entre sus principales diagnósticos diferenciales se encuentran el Síndrome de Stevens-Johnson (SSJ) y Síndrome de Lyell (Necrólisis epidérmica tóxica (NET)). Tiene una incidencia estimada < 1%, siendo su forma mayor levemente más frecuente que su forma menor (0.8-6 por millón/año). Puede darse a cualquier edad, presentando un peak de incidencia entre los 20 y 30 años, predominando ligeramente el sexo masculino con una proporción 3:2, sin predilección racial. Su presentación en edad pediátrica es rara, más aún en la primera infancia. En esta población es más frecuente el EM menor recurrente. En el presente texto se reporta un caso de EM en población pediátrica como una rara forma de presentación exantemática, abordado en el Servicio de Pediatría del Complejo Asistencial Dr Victor Rios Ruiz (CAVRR)en la ciudad de Los Ángeles, Chile en el presente año.

Erythema multiforme (EM) also known as polymorph erythema is an acute skin disease of immunological nature with or without mucous membrane involvement, which may behave as chronic recurrent. It presents with distinctive targets like skin lesions, often together with ulcers or bullae in mucous membranes (oral, genital or ocular). Among its clinical forms are: a minor form characterized by a mild skin syndrome and its major form that manifests as a skin disease with marked mucosal damage. Among its main differential diagnoses are Stevens-Johnson Syndrome (SJS) and Lyell Syndrome (Toxic Epidermal Necrolysis (TEC)). It has an estimated incidence < 1%, with its major form being slightly more frequent than its minor form (0. 8-6 per million/year). It can occur at any age, presenting a peak incidence at the age between 20 and 30 years, with a slight predominance of males with a 3:2 ratio, without racial predilection. Its presentation in pediatric age is rare, even more so in early childhood. Minor recurrent EM is more common in this population. This paper reports a case of EM in the pediatric population as a rare form of exanthematic presentation, addressed at the Department of Pediatrics of the Complejo Asistencial Victor Rios Ruiz (CAVRR) in the city of Los Angeles, Chile this year.

RASopathies: Dermatologists’ viewpoints

Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome/loose anagen hair, Legius syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and capillary malformation-arteriovenous malformation are the well- recognized RASopathies. These are characterized by multi-organ tumours and hamartomas. Some other features in common are facial dysmorphism, skeletal abnormalities, congenital heart disease, neurocognitive abnormalities and risk of various solid-organ and haematological malignancies. Some of the RASopathies are heterogeneous, caused by several gene mutations resulting in variations in phenotypes and severity ranging from mild to fatal. Significant phenotypic overlaps among different disorders, often makes it difficult to pinpoint a clinical diagnosis. Specific cutaneous manifestations are present in some of the RASopathies and are often the earliest clinical signs/symptoms. Hence, dermatologists contribute significantly as primary care physicians by identifying disorder-specific cutaneous lesions. However, diagnostic work-up and management of these disorders are often multidisciplinary. Confirmation of diagnosis is possible only by genetic mapping in each case. Genetic counseling of the patients and the affected families is an important component of the management. The aim of this review is description of cutaneous manifestations of RASopathies in the background of multi-system involvement to enable dermatologists a comprehensive and logical approach to work up and diagnose such patients in the absence of facility for specific molecular testing.

Cardio / 中南大学学报(医学版)

Cardio-facio-cutaneous (CFC) syndrome is an extremely rare autosomal dominant genetic disease due to BRAF and other gene mutations. The main characteristics of the patients are craniofacial deformities, cardiac malformations, skin abnormalities, delay of language and motor development, gastrointestinal dysfunction, intellectual disability, and epilepsy. In this case, the child has a typical CFC syndrome face and developmental delay. The gene results of the second-generation sequencing technology showed that there was a mutation site c.1741A>G (p. Asn581Asp) (heterozygous) in exon 14 of the BRAF (NM_004333.5) gene. The mutation was not observed in the child's parents. The above-mentioned mutation may be a de novo mutation. There is no effective therapy for this disease so far.

Study on application of next-generation sequencing technology in diagnosis of cardio-facio-cutaneous syndrome / 重庆医学

Objective To explore the role of next-generation sequencing(NGS)technology in the assisted diagnosis of RA-Sopathies.Methods Peripheral blood was extracted from 1 child patient with suspected Noonan syndrome and her parents,and the gene mutations were detected by adopting the aCGH and NGS.The results were verified by Sanger sequencing.Results The NGS results revealed that the heterozygous mutation of c.1406G>A existed in BRAF gene,and the results of Sanger sequencing in this child case was consistent with the NGS results.The Sanger sequencing results in her parents showed the locus was G/G wild type. Conclusion This child case was diagnosed as CFC.NGS plays a good auxiliary role in the differentiation diagnosis of RASopathies.

Ross operation in a neuro-cardio-facial-cutaneous syndrome patient.

Congenital heart diseases are a major part of Costello and cardio-facio-cutaneous syndromes. Subaortic stenosis was reported rarely and Ross operation never in these syndromes. We reported a girl patient whose manifestations were consistent with these syndromes. Distinction between these syndromes was not possible as genetic testing was not carried out. She developed severe neoaortic regurgitation 2.5 years after the Ross operation and died due to the complications of aortic valve replacement. Ross operation may be an unsuitable option in these syndromes due to the possibility of subtle pulmonic valve pathology.