RESUMO
Celiac disease (CD) screening in patients with Williams-Beuren Syndrome (WBS) is suggested, although data described in literature are discordant regarding CD prevalence in WBS. We retrospectively collected data from 101 WBS Italian patients [mean age: 13.5 years], to clarify the CD prevalence in a large cohort. All patients underwent a CD biochemical screening: IgA and anti-transglutaminase reflex antibodies (tTGA). CD-specific HLA typing was available for 42 patients. Small intestinal biopsy was performed in patients according to ESPGHAN guidelines. In 7 WBS patients an overt celiac disease was diagnosed. In 3 patients CD was confirmed by symptoms, HLA-DQ heterodimers and CD specific antibodies title, whereas in 4 patients, it was confirmed by a small intestinal biopsy. CD prevalence in our cohort is 6.9% (7/101). In 42/101 patients the CD-specific HLA typing was available, detecting 29/42 (69%) patients genetically predisposed to CD. The CD prevalence and CD-specific HLA prevalence are both higher than in the general population (p < 0.001; p < 0.001). Our cohort is the most numerous described confirming that the CD risk in WBS patients is significantly greater than in general population. Moreover, our HLA typing results, as well as scientific literature, suggest that the higher CD prevalence in WBS patients might not be intrinsically related to the genetic disease itself but with the higher HLA prevalence. However, HLA typing should be performed in bigger WBS cohorts to confirm this hypothesis. Our data confirms that HLA typing is mandatory in WBS patients and that CD screening should be performed only if genetically predisposed.
Assuntos
Doença Celíaca/genética , Testes Genéticos/normas , Síndrome de Williams/genética , Adolescente , Anticorpos/imunologia , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Feminino , Antígenos HLA-DQ/genética , Humanos , Testes Imunológicos/normas , Lactente , Intestino Delgado/imunologia , Intestino Delgado/patologia , Masculino , Transglutaminases/imunologia , Síndrome de Williams/complicações , Síndrome de Williams/diagnósticoAssuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Alelos , Pré-Escolar , Fácies , Feminino , Humanos , Taxa de Mutação , Neurofibromina 1/genética , FenótipoRESUMO
Gastrointestinal stromal tumors (GIST) are tumors of the gastrointestinal (GI) tract originating from the myenteric ganglion cells (interstitial cells of Cajal), that are very rare in children and adolescents. The most common clinical manifestation is acute or chronic, overt or occult GI bleeding although these tumors are asymptomatic in 10-30% of patients. We report a case of gastric GIST in a 11-year-old girl presenting with an iron deficiency refractory anemia without gastrointestinal symptoms and stool evidence of GI bleeding that caused a slight diagnostic delay.
Assuntos
Anemia Ferropriva/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Neoplasias Gastrointestinais/diagnóstico , Criança , Feminino , HumanosRESUMO
Baraitser-Winter malformation syndrome (BWMS), Fryns-Aftimos syndrome (FA), and craniofrontofacial syndromes (CFFs) have all been recently proposed to be part of the same phenotypic spectrum of Baraitser-Winter cerebrofrontofacial syndrome (BWCFF), which is characterized by facial dysmorphism, ocular coloboma, brain malformations, and intellectual disabilities. In addition to that, the recent discovery of missense mutations in one of the two ubiquitously expressed cytoplasmic ß- and γ-acting-encoding genes ACTB (7p22.1) and ACTG1 (17q25.3) in patients carrying a clinical diagnosis of BWSM, FA, or CCF has provided further evidence that these clinical conditions do indeed belong to the same entity at the molecular level. Two cases of BWCFF patients presenting with malignancies (i.e., acute lymphocytic leukemia and cutaneous lymphoma) have been published thus far. Here, we report a 21-year-old female with molecularly confirmed FA, who developed acute myeloid leukemia (AML). The present finding may indicate that actinopathies could be cancer-predisposing syndromes although small numbers and publication bias should be taken into account. © 2016 Wiley Periodicals, Inc.
Assuntos
Anormalidades Craniofaciais/complicações , Epilepsia/complicações , Deficiência Intelectual/complicações , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiologia , Lisencefalia/complicações , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Exame de Medula Óssea , Encéfalo/anormalidades , Hibridização Genômica Comparativa , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Eletrocardiografia , Epilepsia/diagnóstico , Epilepsia/genética , Fácies , Feminino , Testes Genéticos , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Lisencefalia/diagnóstico , Lisencefalia/genética , Imageamento por Ressonância Magnética , Mutação , Translocação Genética , Resultado do Tratamento , Adulto JovemRESUMO
RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
Assuntos
Carcinogênese/genética , Mutação/fisiologia , Fenótipo , Proteínas ras/genética , Animais , Caenorhabditis elegans , Estudos de Coortes , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Juvenil/genética , MAP Quinase Quinase Quinases/metabolismo , Síndrome de Noonan/genética , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais/genética , Proteínas ras/química , Proteínas ras/metabolismoRESUMO
The oncologic involvement of the spinal cord in neurofibromatosis type 1 (NF1) is not a typical feature of the disease. Here, we present a case of ganglioglioma of the spinal cord in a child with NF1 and try to define if this tumor can be considered coincidental or not. A 4-year-old boy affected by NF1 was diagnosed with a spinal cord-enhancing tumor extending from C4 to D3, with a disappearance in the T2 MRI sequences of the cerebrospinal fluid signal. The patient underwent a subtotal resection. The pathological exam revealed a ganglioglioma. To the best of our knowledge, only 1 other case of spinal cord ganglioglioma has been described in an NF1 patient. We suggest considering ganglioglioma in the differential diagnosis of an NF1 patient with a spinal cord tumor due to its favorable survival rate, especially in relation to the anatomical and surgical issues of this tumor that do not always entail a gross total resection.
Assuntos
Ganglioglioma/complicações , Neurofibromatose 1/complicações , Neoplasias da Medula Espinal/complicações , Biópsia , Pré-Escolar , Ganglioglioma/patologia , Ganglioglioma/cirurgia , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Masculino , Neurofibromatose 1/patologia , Neurofibromatose 1/cirurgia , Medula Espinal/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgiaRESUMO
Wolf-Hirschhorn syndrome (WHS) is a rare microdeletion syndrome associated with a characteristic facial appearance, failure to thrive, psychomotor delays, and various major malformations of internal organs; many medical complications have been described (feeding difficulties, epilepsy, hearing problems). Benign or malignant oncologic problems are not a typical feature of the natural history of these patients. We report on two patients with WHS patients in whom hepatic adenoma (HA) were diagnosed during adolescence. The clinical evolution of liver involvement was different between the two. We discuss the possibility of considering HA as a rare medical problem in the follow-up of WHS patients. © 2013 Wiley Periodicals, Inc.
Assuntos
Adenoma/etiologia , Neoplasias Hepáticas/etiologia , Síndrome de Wolf-Hirschhorn/complicações , Adenoma/genética , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , Síndrome de Wolf-Hirschhorn/genética , Adulto JovemRESUMO
This article reports on an association between Burkitt lymphoma and Noonan syndrome (NS) due to a RAF1 gene mutation. The patient was a 7-year-old boy with NS, who was included in the first series reporting the association between Noonan and RAF1, and who later presented with a 2-week history of asymptomatic unilateral tonsillar swelling and ipsilateral cervical lymphadenopathy. Histological and biological examinations of the tonsillar biopsy led to the diagnosis of Burkitt lymphoma. While there is a well-established association between NS and solid cell tumors, this is the first case described in the literature of Burkitt lymphoma in a patient with NS, and adds to the growing list of data supporting neoplasia's association with NS.