Francesca Manzoni

Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management

BackgroundRubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation. However, no standard diagnostic criteria are available for RSTS. In this review, we summarized the clinical features and genetic basis of RSTS and highlighted areas for future studies on an appropriate diagnostic protocol and follow-up care for RSTS.DiscussionRSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe. Over 90% RSTS individuals with disabilities survive to adulthood, but healthcare for these patients is particularly complex, time-consuming, and costly. In addition, no standard diagnostic criteria and follow-up care guidelines are available for RSTS. It has been shown that mutations in the genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the E1A-binding protein p300 (EP300) contributed to the development of RSTS. Therefore, genetic tests are useful for the diagnosis of RSTS, although most RSTS cases are currently diagnosed based on clinical features.SummaryThe clinical features of RSTS have been extensively studied, which significantly contributes to the diagnosis of this extremely rare syndrome. However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown. Therefore, multicenter studies and international cooperation are highlighted for better understanding of this disease, establishing standard diagnostic criteria, and providing professional management and follow-up care of RSTS.

Oropharyngeal and nasopharyngeal sampling for the detection of adolescent Streptococcus pneumoniae carriers

Monitoring the dynamics of pneumococcal carriage makes it possible to evaluate the epidemiological characteristics of Streptococcus pneumoniae disease and the theoretical coverage offered by pneumococcal vaccines. It has been demonstrated that the nasopharyngeal (NP) sampling of respiratory secretions is superior to oropharyngeal (OP) sampling for identifying pneumococci carried by younger children, but adult data are conflicting and there are no published studies of adolescents. In order to compare the efficiency of OP and NP sampling in identifying and quantifying S. pneumoniae carriage in healthy adolescents, 2 swab samples were obtained from 530 adolescents aged 15-19 years, the first taken from the posterior pharyngeal wall through the mouth (OP) and the second through the nose (NP). Bacterial genomic DNA was tested for the autolysin-A-encoding gene (lytA) and wzg (cpsA) gene of S. pneumoniae in order to evaluate pneumococcal carrier status. All of the positive cases were serotyped. S. pneumoniae was identified in 35.8% of the OP swabs and 3.5% of the NP swabs (P<0.0001). The serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) were found in all but two OP samples (98.9%) and only 64.7% of the NP samples (P<0.0001). The most frequently identified PCV13 serotype in both groups was 19F, followed by serotypes 5 and 9V. In conclusion, OP sampling appeared significantly more effective than NP sampling in identifying and characterizing pneumococcal carrier status in adolescents. This suggests that OP sampling should be used when evaluating the dynamics of pneumococcal carriage among adolescents and the theoretical coverage offered by PCV13.

Preliminary evaluation of cord blood platelet gel for the treatment of skin lesions in children with dystrophic epidermolysis bullosa

The common clinical manifestations of EB are mechanical fragility of the skin, blister formation, and abnormal wound healing, but the severity of the skin lesions varies depending on the distinct type of the disease. Junctional EB and dystrophic EB (DEB), the most severe types of EB diseases, usually cause chronic pain and discomfort that can significantly reduce the quality of life of affected

Epidermolysis bullosa and the partnership with autoimmunity: what should we assimilate?

Bullous skin diseases are characterized by genetic abnormalities related to structural epidermal proteins or organ-specific autoantibodies against the same proteins and are revealed by blister formation on skin or mucous membranes, with differences in blister depth, morphology, and topography. Both inherited and autoimmune forms of these disorders can be framed in the context of epidermolysis bullosa. Their clinical spectrum varies from early lethal to mild variants with normal life expectancy, and several distinct phenotypes differ for age of onset, extent, location and depth of skin and mucous lesions, or scarring severity. Recently, different inflammatory processes blended with autoimmune phenomena have been demonstrated in both inherited and acquired epidermolysis bullosa, revealing that this overlapping might cause substantial implications in terms of disease course and outcome. Although several associations between epidermolysis bullosa in its different variants and autoimmune diseases have been reported, it is not yet completely clear how it happens and why this association occurs in only some patients. Autoantibodies are the primary cause of the disease in acquired epidermolysis bullosa, whereas they can be produced as a secondary event due to genetically determined skin damage in inherited epidermolysis bullosa, contributing significantly to the worsening of the disease. The awareness of this overlap may help in identifying new therapeutic approaches with immunosuppressive drugs that could have a significant impact in terms of prognosis.

Preliminary data on immunogenicity, safety and tolerability of trivalent inactivated influenza vaccine in children with inborn errors of metabolism at risk of decompensation.

In order to evaluate the immunogenicity, safety and tolerability of influenza vaccination in children with inborn errors of metabolism (IEMs), we enrolled 20 patients with IEMs at risk of decompensation (14 males; mean age±SD, 8.5±3.9years) and 20 healthy age- and gender-matched controls. Four weeks after vaccination, seroconversion rates were 75-85% and seroprotection rates 85-95%, with high geometric mean titers (GMTs) of all three influenza antigen strains in both groups. Three months after vaccination, most of the subjects remained seroconverted with high seroprotection rates and high GMTs for all the three influenza strains. Safety and tolerability were also very good, with no differences between the groups.

Microdeletion 2q23.3q24.1: Exploring genotype-phenotype correlations

We report a case of a 13‐year‐old girl with a 5.4Mb de novo deletion, encompassing bands 2q23.3q24.1, identified by array‐comparative genomic hybridization. She presented with minor facial and digital anomalies, mild developmental delay during infancy, and behavioral disorders. Few of the reported cases overlap this deletion and all only partially. We tried to compare the clinical features of the patient with the other cases, even though not all of them were molecularly characterized in detail. Considering the neuropsychiatric involvement of the proband and the clinical descriptions of other similar cases, we attempted to identify the genes more probably involved in neurological development and function in the deleted region, particularly GALNT13, KCNJ3 and NR4A2, which are expressed in neuronal cells.

Ehlers-Danlos syndrome versus cleidocranial dysplasia

Dear Sir, The early identification of hereditary syndromes is essential for planning medical and surgical interventions for reducing the risk of complications [1]. Unfortunately, clinical phenotypes of hereditary syndromes in the first years of life and in mild cases are often poorly characterized. Some disease symptoms are also common to several different genetic conditions. Cleidocranial dysplasia (CCD, OMIM #119600) is a genetic condition that predominantly affects the skeletal system. Typical CCD features include persistently open skull sutures, clavicular hypoplasia/aplasia, and dental anomalies [2,3]. CCD is caused by a heterozygous loss-of-function mutation in the RUNX2 gene [2,3]. However, the abnormal shoulder and arm mobility commonly observed in CCD is also typical of other syndromes, particularly hypermobile Ehlers-Danlos syndrome (EDS-HT). EDS-HT is marked by joint laxity with minimal skin changes and no skin fragility [4] but does not have additional specific clinical features and cannot be diagnosed through laboratory tests. The child characterized in this report was initially misdiagnosed with EDS-HT when the correct diagnosis was CCD. CCD was confirmed by genetic findings but not until several years later. The male proband was the second child born to healthy, non-consanguineous Caucasian parents. The family history was unremarkable and did not indicate a history of mental retardation, genetic diseases, or birth defects. The child was born at 35 weeks of gestational age as the result of a premature membrane rupture after an uneventful pregnancy. At birth, he weighed 2,700 gr and had a body length of 45.5 cm, occipital frontal diameter of 30 cm, and an APGAR score of 9/10. The patient’s medical history after reaching school age was unremarkable, and he had normal body and psychomotor growth. However, delayed anterior fontanel closure and prolonged deciduous dentition retention were reported. At nine years of age, the patient experienced constant bilateral shoulder dislocation associated with bilateral flat foot and the delayed eruption of permanent teeth. The patient was evaluated by a pediatrician with experience in the clinical genetics field and was diagnosed with EDS-HT. At 13 years of age, the patient entered the pediatric