RESUMO
PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) gain-of-function has recently been described in patients with recurrent sinopulmonary infections, chronic CMV-/EBV-infections, lymphoproliferation, and hypogammaglobulinemia. Here we report a 15-year-old boy with treatment refractory CMV lymphadenitis, severe combined immunodeficiency, microcephaly and a severe developmental defect of Th17 cells. To avoid poor outcome, hematopoietic stem cell transplantation (HSCT) was performed. Subsequently, whole exome sequencing revealed a de novo heterozygous G-to-C mutation (chr5: 5:67,589,663: G>C) at the splice donor site of the PIK3R1 gene. Our data suggest that PIK3R1 gain-of-function leads to developmental defects in helper and regulatory T-cell subsets, the latter expanding the immunological features of PIK3R1 gain-of-function. T-cell subsets play a critical role in the regulation of immune response against infectious agents and of autoimmunity and thus may be particularly accountable for the clinical phenotype of affected patients.
Assuntos
Infecções por Citomegalovirus , Linfadenite , Microcefalia , Fosfatidilinositol 3-Quinases , Infecções Respiratórias , Adolescente , Classe Ia de Fosfatidilinositol 3-Quinase , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Humanos , Linfadenite/complicações , Linfadenite/genética , Linfadenite/imunologia , Masculino , Microcefalia/complicações , Microcefalia/genética , Seios Paranasais/fisiopatologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/imunologia , Recidiva , Infecções Respiratórias/complicações , Infecções Respiratórias/genética , Células Th17/imunologiaRESUMO
Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY Disorders of Sexual Development (DSD) is characterized by complete gonadal dysgenesis and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth. 46, XY gonadal dysgenesis involves a high risk of gonadoblastoma development with malignant potential such that the onset is greatest at or after the event of puberty. This report of a 12-year-old phenotypic female with 46, XY gonadal dysgenesis, who developed an advanced metastatic seminoma, aims to emphasize the rarity of the development of a seminoma in the context of 46, XY CGD.
RESUMO
BACKGROUND: Despite its rarity, cancer in children and adolescents (CAC) is a major health issue worldwide. The lack of appropriate cancer registries is an obstacle for defining its incidence and survival, and informing cancer control. As in Cyprus, CAC epidemiology has not previously been comprehensively examined, we determined incidence rates and temporal trends of cancer in the 0-19 age group during 1998-2017. METHODS: We established the population based Paediatric Oncology Registry of Cyprus (PORCY) for the period 1998-2017. World age standardised incidence rate per million children and adolescents per year (ASRW) were calculated and time trends were assessed using Joinpoint regression analysis. Comparisons were made with other countries using the International Incidence of Childhood Cancer, third volume. RESULTS: For all cancers combined, for ages 0-19-years, ASRW was 203.54 (95% CI 189.49, 217.59) one of the highest rates globally. The most frequent CAC were leukaemias followed by lymphomas, specified epithelial neoplasms and central nervous system tumours, differing to what is described in most other countries. For all cancers, both combined and individual types, except thyroid carcinoma (where incidence was rising), no significant temporal variation was found. CONCLUSIONS: To inform cancer control activities, we conducted the first ever population-based epidemiological study of childhood and adolescent cancer (0-19 years) in Cyprus. The striking findings indicate high overall incidence rates that are among the world's highest, a higher frequency of lymphomas and thyroid cancer than brain tumours, and rising incidence for thyroid, but not for other, cancers. These novel findings, will help the formulation of hypotheses to provide explanation for the high rates for all CAC in Cyprus and may contribute to the global efforts for improving prevention of cancer in this age group.
Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Neoplasias , Adolescente , Adulto , Criança , Pré-Escolar , Chipre/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias/etiologia , Sistema de Registros , Adulto JovemRESUMO
BACKGROUND: Paediatric and adolescent thyroid cancer incidence rates are increasing in many countries. We determined incidence rates, temporal trends and survival from thyroid cancer diagnosed in childhood and adolescence in Cyprus during 1998-2017. METHODS: Patients aged 0-19 years, diagnosed with thyroid cancer in the Pediatric Oncology Registry of Cyprus were included. Crude incidence rates, age standardized rates, time trends and overall survival were analysed. Annual rates and temporal trends were calculated using Microsoft Excel 2016 and Joinpoint regression analysis. RESULTS: Eighty-one cases (76.5 % female, 23.5 % male) were identified. The crude rates (per 100,000 persons) were for both sexes 2.00 (95 % CI 1.61, 2.49), females 3.15 (95 % CI 2.45, 4.03) and males 0.92 (95 % CI 0.58, 1.44). The annual percentage changes of crude and standardised rates were 7.5 % (pâ¯<â¯0.05) and 7.6 % (pâ¯<â¯0.05). The annual percentage changes of crude rates were for females 5.1 % (pâ¯=â¯0.1), males 8.4 % (pâ¯<â¯0.05) and 15-19-year-olds 7.6 % (pâ¯<â¯0.05). The female to male rate ratio was 3.42 (95 % CI 2.06, 5.74). Papillary thyroid carcinoma represented 86.4 % of all cases. There was only one case after previous cancer therapy. The rate ratio of 2nd (2008-2017) to 1st (1998-2007) periods for metastatic (regional) stages was 3.76 (95 % CI 1.74, 8.31). Survival until 2018 was 100 %. CONCLUSION: This population-based study demonstrated that thyroid cancer incidence rates in 0-19-year-olds in Cyprus was among the world's highest. Increasing trends mainly affected males and females aged 15-19 years with papillary thyroid carcinoma, the dominant type. Cases after previous cancer therapy didn't contribute to increasing rates. The increase of metastatic cases suggests a true increase of thyroid cancer rather than overdiagnosis. Although prognosis is excellent with 100 % survival, the rising incidence rate is unexplained, indicating the need to identify causes.