RESUMEN
BACKGROUND: Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes PTPN11, SOS1, KRAS and RAF1. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: BRAF, KRAS, MEK1 and MEK2. METHODS: A comprehensive mutation analysis of BRAF, KRAS, MEK1, MEK2 and SOS1 in 31 unrelated patients without mutations in PTPN11 is presented. RESULTS: Mutations were identified in seven patients with CFC (two in BRAF, one in KRAS, one in MEK1, two in MEK2 and one in SOS1). Two mutations were novel: MEK1 E203Q and MEK2 F57L. The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC. We thus suggest involvement of BRAF in the pathogenesis of NS also. CONCLUSIONS: Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS-PTPN11-associated or CFC-BRAF-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.
Asunto(s)
Anomalías Craneofaciales/genética , Secuencia de Bases , Niño , Preescolar , Anomalías Craneofaciales/fisiopatología , Análisis Mutacional de ADN , Femenino , Humanos , MAP Quinasa Quinasa 1/genética , MAP Quinasa Quinasa 2/genética , Masculino , Síndrome de Noonan/genética , Síndrome de Noonan/fisiopatología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteína SOS1/genética , Proteínas ras/genéticaRESUMEN
Eleven patients with the so-called Cat Eye syndrome are reported including a more detailed description of the original cases reported by Schmid and Fraccaro. All cases had, in addition to a normal karyotype, a small extra G-like chromosome which appeared to be an isochromosome for the juxtacentromeric region (pter to q11) of an acrocentric chromosome. None were mosaics. Clinical findings and further cytogenetic studies in a few cases suggest that these markers probably derive from a No. 22 chromosome. Characteristic features of the Cat Eye syndrome in these 11 patients and those reviewed from the literature are: ocular coloboma which may involve the iris, choroid and/or optic nerve, preauricular skin tags and/or pits which are probably the most consistent feature, congenital heart defect, anal atresia with a fistula, renal malformations such as unilateral absence, unilateral or bilateral hypoplasia, and cystic dysplasia, and antimongoloid position of eyes. Intelligence is usually low-normal, although moderate retardation is also seen. There is great variability in the clinical findings ranging from near normal to lethal malformations. Less frequent, but also characteristic findings are: microphthalmia, microtia with atresia of the external auditory canal, intrahepatic or extrahepatic biliary atresia and malrotation of the gut. Direct transmission of the marker from one generation to the other was observed in both sexes. In those families, there was considerable variability in the clinical findings between affected family members. These cases show that there is a bias of ascertainment for patients who have the more striking malformations, especially those with ocular coloboma and anal atresia, a combination which appears to be present in only a minority of cases. Many mildly affected patients probably remain undetected. It is proposed that the term Cat Eye syndrome should be applied only to cases with trisomy or tetrasomy of not more than 22pter to q11 and without additional duplication or deletion of another autosomal segment.
Asunto(s)
Aberraciones Cromosómicas/genética , Cromosomas Humanos 21-22 e Y , Anomalías del Ojo , Adolescente , Adulto , Niño , Preescolar , Bandeo Cromosómico , Trastornos de los Cromosomas , Femenino , Humanos , Lactante , Masculino , Fenotipo , Ploidias , Síndrome , TrisomíaRESUMEN
A severe attack of acute polyarthritis following a verified Campylobacter jejuni enteritis is described in a 12-year-old boy. The patient possesses the HLA-B27 antigen--often found in postinfectious arthritis following acute enteric infections. The ASO titre showed a significant rise, but other serological findings and the clinical course made streptococcal infection unlikely. Investigations to elucidate cross-reactivity between the two micro-organisms turned out negative.
Asunto(s)
Artritis/diagnóstico , Infecciones por Campylobacter/complicaciones , Enteritis/complicaciones , Artritis/etiología , Niño , Enteritis/microbiología , Humanos , Masculino , Periartritis/microbiologíaRESUMEN
An 18-week-old baby boy suffered an episode of acute abdominal symptoms followed by a silent period with mild obstructive jaundice, abdominal distension and failure to thrive. During the clinical work-up he deteriorated suddenly, with progressive abdominal distension and ascites. At laparotomy a perforation of the common bile duct with bile peritonitis was found. Spontaneous perforation of the common bile duct is seldom listed as a cause of obstructive jaundice. The clinical picture is characteristic. Awareness of this diagnosis may help to avoid time-consuming and unnecessary investigations and to lead to surgical treatment in good time.