Abramowicz A.,Institute of Mother and Child
Developmental period medicine | Year: 2014
Neurofibromatosis type I (NF1) is a disease associated with the presence of benign neurofibromas and malignant tumours of the central and peripheral nervous system, that are accompanied by characteristic changes in the skin, such as café-au-lait spots or axillary freckling. In 50% of NF1 patients, the clinical symptoms become apparent below 1st year and in 97%, before the age of 8 years. The disease is mainly caused by the presence of mutation in the NF1 gene that encodes neurofibromin - a protein involved in the regulation of several cellular signaling pathways responsible for cell proliferation and differentiation. Neurofibromin is necessary for embryonic development and involved mainly in the differentiation of neural crest derived cells, mesenchymal cells, neural cells, melanocytes and bone cells. Type I neurofibromatosis is inherited in autosomal dominant manner, nevertheless about 50% of detected mutations are de novo ones. The mutations have full penetrance, although they also have significant pleiotropic effect. Over 1485 different mutations have been identified in the NF1 gene so far, most of which lead to a synthesis of truncated, non-functional protein. It is estimated that the point mutations are responsible for approximately 90% of cases of NF1. The remaining 5-7% of NF1 cases are associated with the presence of a single exon or whole NF1 gene deletion (17q11.2 microdeletion syndrome). The article discusses the role of neurofibromin in cell signaling with the special attention to RAS/MAPK pathway regulation as well as in organism development. Also the basic methods of molecular analysis of NF1 gene are presented in the context of their application in the diagnosis and clinical differentiation of the disease.
Bezniakow N.,Institute of Mother and Child
Developmental period medicine | Year: 2014
The RASopathies are a class of developmental syndromes. Each of them exhibits distinctive phenotypic features, although there are numerous overlapping clinical manifestations that include: dysmorphic craniofacial features, congenital cardiac defects, skin abnormalities, varying degrees of intellectual disability and increased risk of malignancies. These disorders include: Noonan syndrome, Costello syndrome, LEOPARD syndrome, cardio-facio-cutaneous syndrome (CFC), capillary malformation-arteriovenous malformation syndrome (CM-AVM), Legius syndrome and neurofibromatosis type 1 (NF1). The RASopathies are associated with the presence of germline mutation in genes encoding specific proteins of the RAS/mitogen - activated protein kinase (MAPK) pathway that plays a crucial role in embryonic and postnatal development. In this review, we present the clinical and molecular features of selected syndromes from the RASopathies group.
Jodkowska M.,Institute of Mother and Child
Medycyna wieku rozwojowego | Year: 2011
To investigate the differences in the dietary patterns of Polish overweight and normal weight adolescents. The study was carried out on a group of 1906 pupils from gymnasium (lower secondary school) aged 13-15 years, of whom 953 were overweight and 953 had normal body mass. The sample was taken from a representative group of 8386 pupils. Their height and body weight were measured, and their BMI was calculated. Overweight was defined as BMI ł85 percentile for gender and age. Using the method of "selection in pairs", each overweight pupil was paired with a pupil with normal body weight. The research tool was a self-reported questionnaire, containing questions regarding how often selected food products were usually consumed during the week, how regularly basic meals (breakfast, lunch, supper) were eaten, and data on snacking. Overweight adolescents consumed unhealthy products such as sweets and crisps significantly less often than their peers with appropriate body mass. Overweight girls ate dark bread significantly more often, and consumed soft drinks less often than their peers with normal weight. Overweight adolescents had more irregular meals than those with normal weight: only 44% overweight adolescents had breakfast every day, significantly less than adolescents with normal weight. Nevertheless, overweight teenagers snacked significantly less often than young people with normal body mass. The overweight teenagers also less often chose snacks with high fat content, sugar and salt, and more often vegetables, fruits, as well as yoghurt and kefir. 1. Our study shows that compliance of low energy diet alone does not ensure the maintenance of normal body weight. Irregularity of meals and breakfast skipping play an important role in developing overweight and obesity in adolescents. 2. In future studies on dietary patterns in a larger sample of adolescents, emphasis should be placed on adding questions about portion size, food preparation and meal time. Eating behaviours of parents should be also examined in relation to their body weight.
Derwinska K.,Institute of Mother and Child
Medycyna wieku rozwojowego | Year: 2012
Congenital heart defects are the most common group of major birth anomalies and one of the leading causes of infant deaths. Mendelian and chromosomal syndromes account for about 20% of congenital heart defects and in some cases are associated with other malformations, intellectual disability, and/or dysmorphic features. The remarkable conservation of genetic pathways regulating heart development in animals suggests that genetic factors can be responsible for a significantly higher percentage of cases. Assessment of the role of CNVs in the etiology of congenital heart defects using microarray studies. Genome-wide array comparative genomic hybridization, targeting genes known to play an important role in heart development or responsible for abnormal cardiac phenotype was used in the study on 150 patients. In addition, we have used multiplex ligation-dependent probe amplification specific for chromosome 22q11.2 region. We have identified 21 copy-number variants, including 13 known causative recurrent rearrangements (12 deletions 22q11.2 and one deletion 7q11.23), three potentially pathogenic duplications (5q14.2, 15q13.3, and 22q11.2), and five variants likely benign for cardiac anomalies. We suggest that abnormal copy-number of the ARRDC3 and KLF13 genes can be responsible for heart defects. Our study demonstrates that array comparative genomic hybridization enables detection of clinically significant chromosomal imbalances in patients with congenital heart defects.
Cudzilo D.,Institute of Mother and Child
Developmental period medicine | Year: 2015
Velo-Cardio-Facial syndrome (VCFS), also called 22q11.2 microdeletion syndrome, is a rare pathology. The syndrome is caused by 22q11.2 deletion, recognized as one of the most frequent pathogenic human microdeletions. The scope and severity of the phenotypic expression of 22q11.2 microdeletion is characterised by high variability, although cleft palate and congenital conotruncal malformations are among the clinical features often associated with that syndrome. In the presented case of a boy patient with submucous cleft palate and congenital cardiac defect, 22q11.2 microdeletion was identified at the age of 13 months. In the presented paper particular emphasis was placed on the issue of dental and orthodontic care in patients with changes in the oral cavity and the craniofacial area, as well as on the possibilities of treatment and prophylaxis. The necessity to perform a thorough examination of the oral cavity in infants was also underlined as a vital element of clinical assessment, in particular in the case of co-occurring structural defects of internal organs.