Mutación c.3037G>A en el gen FBN1 asociado a síndrome de Marfan variante neonatal / Mutation c.3037G>A in the FBN1 gene associated with neonatal Marfan syndrome variant

Resumen: El síndrome de Marfan ([SM], OMIM 154700) es un trastorno del tejido conectivo que exhibe un patrón de herencia autosómico dominante, cuyas características clínicas pueden afectar de forma variable múltiples sistemas u órganos. Es causado por mutaciones en el gen FBN1 (OMIM 134797) localizado en 15q21.1. El SM neonatal es una variedad infrecuente de la entidad asociado con mutaciones en el cambio de sentido entre los exones 23-33 y mutaciones truncadas, exhibe un fenotipo más severo y alto porcentaje de mortalidad en los primeros años de vida. Se presenta el caso de adolescente masculino con SM neonatal y mutaciones en el cambio de sentido (c.3037G>A; p.Gly225Arg) en el exón 24 del gen FBN1. Ante estos hallazgos se estudió la variación fenotípica interfamiliar, la evaluación médica interdisciplinaria precoz necesaria para el manejo de las posibles complicaciones, así como el oportuno asesoramiento genético familiar.

Abstract: Marfan syndrome ([MS], OMIM 154700) is a connective tissue disorder that exhibits an autosomal dominant pattern of inheritance, whose clinical characteristics can affect multiple systems or organs in a variable way. It is caused by mutations in the FBN1 gene (OMIM 134797) located at 15q21.1. Neonatal MS is an uncommon variety of the entity associated with missense mutation between exons 23-33 and truncating mutations, exhibits a more severe phenotype and high percentage of mortality in the first years of life. The case of male adolescent with neonatal MS and missense mutation (c.3037G> A; p.Gly225Arg) in exon 24 of the FBN1 gene is presented. Given these findings, interfamilial phenotype variation, the early interdisciplinary medical evaluation necessary for the management of possible complications, as well as the appropriate family genetic counseling were studied.

Medical conditions of children and young people with Down syndrome.

BACKGROUND: The life expectancy of people with Down syndrome (DS) has significantly increased in the last decades. We describe the congenital malformations and main comorbidities of a cohort of children and young people with DS and analyse their differences according to age and gender groups. METHODS: This retrospective cross-sectional study was conducted at DS centre of Bambino Gesù Children's Hospital in Rome (Italy). The period for reviewing all electronic health records ran from July 2016 to September 2017. We collected data on clinical conditions and compared them with the general paediatric population. Moreover, we compared the main comorbidities, dental diseases and body mass index data between age groups. RESULTS: Seven hundred sixty-three children and young people with DS included in this study were aged 7.45 ± 5.49 years. Gender distribution included 58.19% male patients. The majority of our population (71.04%) came from central regions of Italy. Respiratory diseases (19%), congenital heart defects (72.23%), malocclusions (58.62%), astigmatism (20.31%), farsightedness (16.51%), near-sightedness (12.19%) and autoimmune hypothyroidism (3.28%) were more frequent in our population compared with the typical paediatric population. Upper respiratory tract infections and underweight were significantly more frequent in the youngest children, whereas dental diseases, refractive errors, obesity and autoimmune hypothyroidism increased over age. CONCLUSIONS: Children and young people with DS present a high prevalence of potentially treatable medical conditions making multidisciplinary teams a mandatory need for this population.

[Mutation c.3037G>A in the FBN1 gene associated with neonatal Marfan syndrome variant]. / Mutación c.3037G>A en el gen FBN1 asociado a síndrome de Marfan variante neonatal.

Marfan syndrome ([MS], OMIM 154700) is a connective tissue disorder that exhibits an autosomal dominant pattern of inheritance, whose clinical characteristics can affect multiple systems or organs in a variable way. It is caused by mutations in the FBN1 gene (OMIM 134797) located at 15q21.1. Neonatal MS is an uncommon variety of the entity associated with missense mutation between exons 23-33 and truncating mutations, exhibits a more severe phenotype and high percentage of mortality in the first years of life. The case of male adolescent with neonatal MS and missense mutation (c.3037G> A; p.Gly225Arg) in exon 24 of the FBN1 gene is presented. Given these findings, interfamilial phenotype variation, the early interdisciplinary medical evaluation necessary for the management of possible complications, as well as the appropriate family genetic counseling were studied.

El síndrome de Marfan ([SM], OMIM 154700) es un trastorno del tejido conectivo que exhibe un patrón de herencia autosómico dominante, cuyas características clínicas pueden afectar de forma variable múltiples sistemas u órganos. Es causado por mutaciones en el gen FBN1 (OMIM 134797) localizado en 15q21.1. El SM neonatal es una variedad infrecuente de la entidad asociado con mutaciones en el cambio de sentido entre los exones 23-33 y mutaciones truncadas, exhibe un fenotipo más severo y alto porcentaje de mortalidad en los primeros años de vida. Se presenta el caso de adolescente masculino con SM neonatal y mutaciones en el cambio de sentido (c.3037G>A; p.Gly225Arg) en el exón 24 del gen FBN1. Ante estos hallazgos se estudió la variación fenotípica interfamiliar, la evaluación médica interdisciplinaria precoz necesaria para el manejo de las posibles complicaciones, así como el oportuno asesoramiento genético familiar.

Neonatal teeth: Importance of histological findings in management update.

BACKGROUND: Presence of teeth in a newborn represents a rare finding and a disturbance of biological chronology of teeth. The aim of this paper is to report two cases with neonatal teeth histologically examined. CASE REPORT: In this paper two cases of patients with neonatal teeth are reported and histological examinations of three extracted teeth are described. We report an exceptional finding in one of the neonatal teeth microscopically examined: a massive inflammatory infiltration in the pulp tissue similar to that in pulpitis. RESULTS: The management of natal and neonatal teeth usually includes the extraction in case of ulceration on the tongue or severe tooth mobility to prevent accidental inhalation or feeding disturbances. The presence of an inflammatory infiltration of pulp tissue in one of teeth histologically examined suggests to review the indications for extraction considered to date. CONCLUSION: The management of natal and neonatal teeth should consider the presence of an inflammatory infiltration of pulp tissue. An anamnestic interview is advisable in ordert to deeply investigate about possible behaviours of the child due to pain or discomfort.

Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child. METHODS: An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. RESULTS AND CONCLUSION: The diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up. Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

A case of Invasive Cervical Root Resorption in a 12 y.o. female patient.

Invasive Cervical Root Resorption (ICRR) has a poor known aetiology, compared with typical external root resorption it appears very aggressive, posing a high risk of tooth loss. ICCR is often misdiagnosed, the resorption is caused by cells of the peridontium penetrating the outer surface of the root in the cervical region, spreading out throughout the root dentin. ICCR is usually detected in the adulthood on permanent teeth, anyway in a small amount of cases is possible to observe ICCR on impacted permanent canines during the adolescence and first adulthood.The aim of this paper is to present our experience with a ICCR case occurred in a young woman previously treated for an impacted canine with orthodontic therapy.

Nitrous oxide occupational exposure in conscious sedation procedures in dental ambulatories: a pilot retrospective observational study in an Italian pediatric hospital.

BACKGROUND: Nitrous oxide has a proven clinical efficacy in conscious sedation. At certain environmental concentrations it may pose a health risk to chronically exposed healthcare workers. The present pilot study aims at evaluating the exposure to nitrous oxide of dental ambulatory personnel of a pediatric hospital. METHODS: A descriptive study design was conducted in two phases: a bibliographic analysis on the environmental safety policies and a gas concentration analysis in the dental ambulatories of a pediatric hospital, detected every 6 months from December 2013 to February 2017 according to law provisions. The surveys were carried out using for gas analysis a photoacoustic spectrometer Innova-B&K "Multi-gas monitor model 1312" and Innova-B&K "Multi-sampler model 1309". The biological analysis and monitoring have been carried out on staff urine. RESULTS: The analyses were performed during 11 dental outpatient sessions on pediatric patients. All the patients were submitted to the same dental procedures, conservative care and dental extractions. The pediatric patients were 47 (23 males, 24 females; age range 3-17 years; mean age 6,63, SD ± 2,69) for a mean of 4,27 (SD ± 1,49) per session., The mean environmental concentration of nitrous oxide during the sessions was 24.7 ppm (SD ±16,16). A correlation was found between urinary nitrous oxide concentration of dentists (Pearson's correlation 0.786; p = 0.007) and dental assistants urines (Pearson's correlation 0.918; p < 0.001) and environmental concentrations of nitrous oxide. Weak negative correlations were found between age and sex of patients and environmental concentrations of nitrous oxide. The mean values of the biological monitoring data referring to all the outpatient sessions are lower than the reference values foreseen in accordance to the regulations in force on nitrous oxide concentration. CONCLUSIONS: The mean environmental concentration values recorded in our study are below the limit of 50 ppm considered as a reference point, a value lower than those reported in other similar surveys. The results of the present study provide a contribution to the need to implement technical standards, criteria and system requirements for the dental ambulatories, to date not yet completely defined, and cannot be assimilated to the ones established for the surgical rooms.

Correlation between cephalometric variables and obstructive sleep apnoea severity in children.

AIM: Alterations in craniofacial growth have been associated with obstructive sleep apnoea in children. The main objectives of this study were to analyse the correlation between cephalometric variables and Obstructive Apnea/Hypopnea Index (OAHI) in order to investigate if craniofacial features may influence the severity of obstructive sleep apnoea and to study the correlation between upper nasopharyngeal width and maxillomandibular skeletal discrepancy in sagittal and vertical plane. MATERIALS AND METHODS: Study Design: Correlations between cephalometric variables and obstructive sleep apnoea/hypopnea index and between upper airways space and maxillomandibular skeletal discrepancy were investigated. Forty-seven children with obstructive sleep apnoea diagnosed by overnight sleep study (polysomnography) underwent a lateral radiograph, orthodontic and ear-nose-throat examinations. Cephalometric analysis according to Kirjavainen has been performed to define skeletal and upper airways variables. STATISTICS: Spearman's correlation analysis was performed between OAHI and all cephalometric variables. Pearson's correlation analysis was performed between cephalometric variables of upper airway space and cephalometric variables related to maxillomandibular discrepancy. Chi-square test was used to compare occlusal features with adenoidal and tonsillar hypertrophy. Kruskal-Wallis rank test was used to compare OAHI with occlusal variables and adenotonsillar hypertrophy. RESULTS: The results show a positive correlation between OAHI and maxillomandibular discrepancy measured by ANB angle (rho=0.32; p=0.023). A significant correlation was found between upper nasopharyngeal width and vertical maxillomandibular skeletal discrepancy: 1) ad1-PNS were correlated to Mandibular Plane/Sella- Nasion angle (r=-0.36; p=0.012), Palatal Plane/Mandibular Plane angle (r=-0.39; p=0.007), and Posterior-Anterior Facial Height % (r=0.29; p=0.045); 2) ad2-PNS was correlated to Palatal Plane/Mandibular Plane angle (r=-0.39; p=0.007). No statistically significant differences were found in non-parametric tests between OAHI and occlusal variables or adenoidal and tonsillar hypertrophy. CONCLUSIONS: The present study shows a significant correlation between maxillomandibular discrepancy and the severity of OSA. Moreover, the reduction of nasopharyngeal width was correlated to maxillomandibular hyperdivergent growth pattern. These results support the presence of a correlation between sleep-disordered breathing and craniofacial features even if the cause-effect relation is still unclear. Based on these evidences, we suggest the importance of orthodontic evaluation in the management of paediatric OSA.

Evaluation of the relationship between obesity, dental caries and periodontal disease in adolescents.

AIM: To assess the prevalence of caries, oral hygiene quality and periodontal disease in a cohort of obese adolescents compared to a control group. MATERIALS AND METHODS: Study Design: cross-sectional study conducted on 204 subjects (age range 10-16 years). Ninety obese subjects (BMI >90) and 114 normal-weight subjects (BMI <75) were visited at the Bambino Gesù Children's Hospital and in a junior high school in Rome, respectively. An ad hoc questionnaire (investigating demographic and oral health behaviour data) was filled in by patients and their caregivers. Accurate oral examinations were conducted. The Decayed-Missing-Filled Teeth/Surfaces Index in both permanent (DMFT/DMFS) and primary dentition (dmft/dmfs), Gingival Bleeding Index (GBI), Visible Plaque Index (VPI), and Probing Depth (PD) were recorded. STATISTICS: data analysis was carried out using the Statistical Package for the Social Sciences (SPSS 21.0; SPSS IBM, New York, NY). The data of the two groups were compared by means of Student's t Test or the Mann-Whitney test for numerical data and the Chi-square test for categorical data. RESULTS: Patients affected by obesity, compared with controls, presented less compromised teeth in the primary dentition (dmft obese: 0.30 ±± 1.12; normal-weight: 1.00 ± 1.90; P<0.001) and less compromised dental surfaces (dmfs obese: 0.51 ± 2.14; normal-weight: 1.61 ± 3.10; P<0.001). Furthermore obese patients showed minor gingival inflammation with less bleeding on probing (GBI) (obese: 23.95 ± 21.43; normal-weight: 38.17± 24.37; P<0.001), and less probing depth in a greater number of sites (PPD ≤ 3) (obese: 101.92 ± 9.27; normal-weight: 97.28 ± 12.13; P<0.001). Moreover, the obese group showed a better oral hygiene (VPI) (obese: 25.69 ±25.83; normal-weight: 37.72 ±24.34; P<0.001). CONCLUSION: In our study, obese adolescents showed a better oral hygiene, fewer compromised teeth and better periodontal health when compared with normal-weight patients.

Effects of simultaneous palatal expansion and mandibular advancement in a child suffering from OSA.

This clinical report describes a child suffering from obstructive sleep apnoea (OSA) and class II skeletal malocclusion with maxillary contraction and anterior open bite. He presented moderate obstructive sleep apnoea with large impact on quality of life of patient and parents. He was treated using an innovative orthodontic device (Sleep Apnea Twin Expander) to simultaneously carry out palatal expansion and mandibular advancement. After orthodontic therapy, the OSA-18 questionnaire demonstrated an improvement of the main respiratory symptoms, while cardiorespiratory sleep study revealed a reduction in obstructive sleep apnoea events. Post-treatment, clinical assessment and cephalometric analysis showed a reduction of sagittal maxillary discrepancy and an extension of upper airway space. In conclusion, this case report suggests that orthodontic treatment might be a valuable alternative treatment in children with obstructive sleep apnoea related to craniofacial anomalies.

Ligneous periodontal lesions in a young child with severe plasminogen deficiency: a case report.

BACKGROUND: Ligneous periodontitis or gingivitis is a rare periodontal disorder, secondary to plasminogen deficiency, characterised by nodular gingival enlargements and progressive destructive membranous periodontal disease. CASE REPORT: We describe the early and successful dental management of a case of ligneous gingivitis secondary to plasminogen deficiency in a 6-year- old girl. The patient was referred because of a nodular asymptomatic gingival hypertrophy with ulceration around the eruption site of tooth 36, without any detectable tooth mobility. After non-surgical management of the lesion and strict follow-up, the first molar erupted completely, with no signs of bone and periodontal disease. CONCLUSION: Ulcerated periodontal lesions could represent the ?rst signs of plasminogen deficiency. The early treatment is essential in preventing infections and the onset of a destructive periodontitis. The paediatric dentist may play a key role in early diagnosis and treatment.

Efficacy of the Sander bite-jumping appliance in growing patients with mandibular retrusion: a randomized controlled trial.

OBJECTIVES: The efficacy of functional appliances remains highly debated. This randomized controlled trial investigated the skeletal and dentoalveolar effects determined by the Sander bite-jumping appliance (BJA). The null hypothesis to be tested was that the appliance would not induce supplementary mandibular growth compared to untreated controls. SETTING AND SAMPLE POPULATION: This study was carried out at the Section of Orthodontics, University of Naples Federico II, Italy. Forty-six patients receiving a clinical diagnosis of skeletal and dental class II due to mandibular retrusion were either allocated to a treatment (23 patients;15 boys, 8 girls; mean age ± SD: 10.9 ± 1.3 years) or to an untreated control group (23 patients;11 boys, 12 girls; mean age ± SD: 10.5 ± 1.2 years), by using a balanced block randomization. METHODS: Lateral cephalograms were taken before and after treatment and used for comparisons. Measurements were analyzed by descriptive statistics, univariate and multivariate statistical tests. RESULTS: Treated individuals had a significant increase in mandibular length (6.4 ± 2.3 vs. 3.5 ± 2.5 mm; p < 0.001), overjet reduction (-5.0 ± 2.9 vs. 0.3 ± 1.2 mm; p < 0.001) and molar relationship improvement (-5.3 ± 2.4 vs. 0.1 ± 1.1 mm; p < 0.001) compared to controls. The use of the appliance did not significantly affect jaw divergence. Proclination of lower incisors was slightly greater (3.0°, p = 0.023) in treated patients than in controls. The increase in mandibular length was not significantly influenced by cervical stage (p = 0.40). CONCLUSION: The BJA can effectively correct class II malocclusions by a combination of dentoalveolar and skeletal effects. The long-term stability of the correction needs to be evaluated.

[The pediatrician faced with the child with a valvular prosthesis]. / II pediatra di fronte al bambino portatore di protesi valvolare.

Among the acquired or congenital valvular dysfunctions that require conservative valvuloplastic surgical intervention or valvular replacement, the rheumatic valve disease is reported in a limited number of cases among the developed countries, while it is frequent in those with precarious socio-economic conditions. In these countries there are many cases of rheumatic valve diseases during childhood, quickly leading to serious health conditions to require valve replacement during second and third childhood. On the contrary, in the more developed countries, congenital valvular disease prevail by far. The child who underwent valve replacement, once dismissed from cardio-surgical centre, must be nursed domiciliary by his family pediatrician. This assistance consists in a strict supervision for a precocious identification of valvular prosthesis dysfunctions and possible embolic and hemorrhagic complications and in supplying anticoagulant therapy. For this purpose it is important to refer to a well equipped cardiological centre. Besides these fundamental tasks there are others - equally important - directed to preserve health: curing each pathological extracardiac event, intercurrent or recurrent; preventing, with or without compulsory vaccinations, infectious childhood's diseases; preventing especially bacterial endocarditis as the most frequent cause of prosthesis pathology. This work pays particular attention to bacterial endocarditis (prophylaxis and cure). Thromboembolism and anticoagulant therapy (with the list of coumarin drug interventions) have also been dealt. Moreover we have reported brief indications on the prevention and/or cure of diseases for which vaccination is not compulsory, such as: measles, chicken-pox, whooping-cough, typhus, influenza. Our script ends with good suggestions on nourishment and physical activity.