S100B as a new fecal biomarker of inflammatory bowel diseases.

OBJECTIVE: S100 proteins are demonstrated to exert a protective role in the gastrointestinal tract. In the present study, we investigated whether S100B protein, that is typically expressed by enteroglial cells, is detectable in feces and could be a useful noninvasive indicator of gut chronic inflammation. PATIENTS AND METHODS: This clinical prospective study included n=48 patients suffering Crohn's disease (CD) or ulcerative colitis (UC) and non IBD-controls. The clinical disease activity was evaluated using Harvey-Bradshaw or Mayo Score Index while the diagnosis of IBD was defined based on standard endoscopic and histological criteria. S100B and calprotectin were extracted and analyzed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Unlike calprotectin, S100B was significantly decreased in both CD and UC compared to non IBD-patients. The strongest quantitative alterations of S100B were detected concomitantly with signs of active or quiescent disease, including high/normal expression of fecal calprotectin, mucosal damage/cryptitis, mucin depletion and inflammatory infiltrate, as defined by endoscopic evaluation and histological analysis. At the onset of disease and under no Infliximab-based therapy, the lowest was detected suggesting that S100B in feces could have a potential diagnostic value for IBD. CONCLUSIONS: Testing for S100B and calprotectin could be a useful screening tool to better predict IBD activity.

The role of echocardiography in the evaluation of cardiac damage in hypertensive obese patient.

Obesity rates are rising worldwide. Often obesity is associated with hypertension leading to an increased cardiovascular risk. Both obesity and hypertension induce several modifications in cardiac structure and function, particularly atrial and ventricular remodeling is a common finding shared by these two conditions. It has been demonstrated obesity leads to: left ventricular (LV) mass increase, LV systolic and diastolic dysfunction, left atrium (LA) size increase, LA function alterations and pericardial fat accumulation. Nowadays, the development of cardiac imaging techniques allows to early identifying any preclinical damage related to hypertension and obesity. This could be very important in order to improve patient management and medical therapy.

Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future.

Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children's healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn's place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia associated with keratoconus.

Hypohidrotic ectodermal dysplasia (HED) was first described in 1848 by Thurnam. HED belongs to ectodermal dysplasias (EDs), which are developmental impairments of ectodermal-derived tissues. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the EDs and consists in abnormal development of teeth, hair, and eccrine sweat glands. XLHED is determined by mutations in the ED1 gene, which is responsible for the coding of ectodysplasin-A(EDA-A), a protein that regulates ectodermal appendage formation. In the present study we found both in our proband and in the mother the same missense mutation in exon 9 (c.957 C>A), which resulted in an aminoacid change at position 319 (Ser319Arg). This latter anomaly might alter the charges in the TNF domain of EDA-A, affecting the stability of the protein and therefore the interaction with its receptor. The male propositus presented classical manifestations of HED except for keratoconus (KC) and, to the best of our knowledge, this association has not been previously described. The identification of this new mutation may contribute to evaluating the genotype/phenotype correlations. Finally, this report can give useful information about the genetic basis of KC and HED. Future studies will allow us to understand if a genetic bond exists between them.

Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. METHODS: The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum of the syndrome. They next assessed whether histone acetylation levels were altered in these cell lines. RESULTS: The comparison of CREBBP-mutated RSTS cell lines with cell lines derived from patients with an unrelated mental retardation syndrome or healthy controls revealed significant deficits in histone acetylation, affecting primarily histone H2B and histone H2A. The most severe defects were observed in the lines carrying the whole deletion of the CREBBP gene and the truncating mutation, both leading to a haploinsufficiency state. Interestingly, this deficit was rescued by treatment with an inhibitor of histone deacetylases (HDACi). CONCLUSIONS: The authors' results extend to humans the seminal observations in RSTS mouse models and point to histone acetylation defects, mainly involving H2B and H2A, as relevant molecular markers of the disease.

Neonatal presentation of Prader Willi sindrome. Personal records.

Prader Willi Syndrome (PWS) is characterized by typical appearance, obesity, short stature, hypothalamic hypogonadism, cryptorchidism, hypotonia, behavioural abnormalities and mental retardation. It is considered as a continuous genes syndrome with different genotypes: microdeletion of the region 15q11-q13 with paternal imprinting; maternal uniparental disomy (UPD) of chromosome 15; chromosomal rearrangement. Clinical manifestations evolve with age from newborn (hypotonia, poor sucking, hypoplastic external genitalia) to childhood (delay in psychomotor development, hyperphagia, obesity, acromicria and craniofacial dysmorphisms). We present five newborns who received an early diagnosis, based on clinical presentation. The early treatment and follow-up can in fact improve the natural evolution of the syndrome in order to prevent respiratory tract diseases and obesity, and to improve growth.

Maternal hyperphenylalaninemia syndrome: neuropsychological evaluation of four subjects during childhood and adolescence.

Maternal hyperphenylalanemia during pregnancy may induce a severe embryopathy characterized by microcephaly, mental retardation, facial dysmorphy and congenital heart defects. Four subjects, two pairs of sibs, with maternal hyperphenylalaninemia syndrome were included in this study and their neuropsychological performances were assessed. Maternal levels of hyperphenylalaninemia were similar in both mothers, one of them had not been diagnosed with the condition until her two children were examined at the ages of 10 and 6 years. A severe cognitive deficit was detected in all 4 subjects, with a typical profile of impaired perceptive abilities, behavioural disturbances, motor difficulties and poor familiar integration.

Evaluation of cytokine polymorphisms (TNFalpha, IFNgamma and IL-10) in Down patients with coeliac disease.

BACKGROUND: In Down syndrome there is an increased prevalence of coeliac disease, but the reasons for this association are yet unknown. AIMS: To evaluate a possible correlation between TNFalpha, IFNgamma and IL-10 genotype polymorphisms with the susceptibility to coeliac disease in Down syndrome patients. METHODS: Single nucleotide polymorphisms of TNFalpha (-308G-->A promoter region), IFNgamma (+874T-->A promoter region) and IL-10 (-1082G-->A promoter region) have been studied in 10 Down patients with coeliac disease, in 40 Down patients without coeliac disease and in 220 healthy controls. Clinical features were also studied in coeliac disease-Down syndrome patients. RESULTS: The 10 coeliac disease-Down syndrome patients had a biopsy proven coeliac disease afterward a serological testing positive to antigliadin, antiendomysium and antitransglutaminase antibodies. Intestinal biopsy showed total atrophy in 6/10 and partial villous atrophy in 4/10 of them. All coeliac disease-Down syndrome patients had silent forms of coeliac disease and classical trisomy 21. No significant differences were observed for the IFNgamma and IL-10 polymorphisms in the studied groups. A significant trend for increase of TNFalpha -308A positive frequency was observed in coeliac disease-Down syndrome patients compared to healthy controls (p=0.043). CONCLUSIONS: Single nucleotide polymorphisms of IFNgamma and IL-10 do not play a role in predisposing Down syndrome patients to coeliac disease, while the TNFalpha -308 allele could be an additional genetic risk factor for coeliac disease in trisomy 21.

Down syndrome and breastfeeding.

AIM: The aim of the study was to investigate the frequency of breastfeeding among children with Down syndrome. METHODS: The mothers of 560 children with Down syndrome attending four university hospitals in Italy were interviewed and the neonatal clinical records retrieved. Information was collected on the type of infant feeding and on why some mothers had not breastfed their children. Two groups of healthy children whose feeding habits had been previously investigated were recruited as control subjects (1601 and 714, respectively). A paediatrician in each hospital was interviewed about the neonatal admission policy of children with Down syndrome. RESULTS: Among the 560 Down children, 246 (44%) were admitted to the neonatal unit. Compared with the two control groups, children with Down syndrome were significantly more frequently bottle-fed (57% vs 15% and 24%, respectively, odds ratio 7.5, 95% CI 6.0-9.4 and 4.2, 95% CI 3.3-5.4. respectively). Only 30% of infants admitted to the neonatal unit were breastfed. The main reasons reported by the mothers for not having breastfed were infants' illness in infants who had been admitted to the neonatal unit and frustration or depression, perceived milk insufficiency and difficulty with suckling for those babies who had not been admitted to the unit. The paediatricians reported that the admission of a baby with Down syndrome to the neonatal unit could sometimes take place not for medical reasons, but for diagnostic work-up or for a more appropriate diagnosis and to maintain communication with the family. CONCLUSIONS: Down syndrome babies are less frequently breastfed compared with healthy children. Support in breastfeeding should become a relevant point of health supervision for children with Down syndrome.

Autosomal recessive severe dwarfism in a Sicilian girl: a new form of osteodysplastic primordial dwarfism?

A new type of osteodysplastic primordial dwarfism is delineated in a 5-year-old female child with severe growth retardation of prenatal onset, gross skeletal changes, a non-Seckel facial phenotype, and presumed autosomal recessive inheritance.

Lymphoproliferative disorders in Sotos syndrome: observation of two cases.

Sotos syndrome is included among the overgrowth disorders, most of which have an increased risk of neoplasms. Sotos syndrome does not appear to be related to a specific tumor type, but rather to the development of solid tumors of ectodermal or mesodermal origin in general. We report on two Sotos syndrome patients who developed a non-Hodgkin lymphoma and an acute lymphoblastic leukaemia, respectively. Our experience suggests that there may exist a high frequency of lymphoproliferative disorders in Sotos syndrome, and points out the importance of a long-term follow-up of Sotos syndrome patients, to detect a possible neoplastic evolution.

Craniofacial fibrous dysplasia and Ollier's disease: combined transfrontal and transfacial resection using the nasal-cheek flap.

Fibrous dysplasia and Ollier's disease (skeletal chondromatosis) are bone lesions that result from disorders occurring during ossification. Here we report on a patient suffering from Ollier's disease in whom polyostotic fibrous dysplasia was detected. The main problem for this 20-year-old man was a nasoethmoidorbital cartilaginous mass causing nasal obstruction, nonreducible eye proptosis, and sleep apnea. The lesion was approached by means of a combined route, ie, transfrontally and transfacially (nasal-cheek flap). The possible pathogenetic links existing between the two lesions and the problems involved in surgical treatment are discussed.

New syndrome: autosomal dominant microcephaly and radio-ulnar synostosis.

To date, the combination of microcephaly and radio-ulnar synostosis has not been recognized as a distinct clinical and genetic entity. We report on 4 familial cases with this previously undescribed combination of defects, showing autosomal dominant inheritance (Fig. 1).

[The follow-up of malformation uropathies diagnosed "in utero"]. / Il follow-up delle uropatie malformative diagnosticate "in utero".

Prenatal diagnosis and postnatal follow-up of urinary tract congenital malformations are discussed. Among 9501 overall births, 25 newborns with urinary tract congenital malformations were born (2.6 x 1,000). Twenty cases had been diagnosed "in utero" by ultrasound scan (4 cases of Potter sequence, 2 cases of prune-belly anomaly, 3 cases of polymalformed infants with urinary involvement, 10 cases of hydronephrosis, 1 case of ectopic kidney). In 8 newborns a surgical treatment was successfully performed. Eight newborns died and in other 4 cases clinical and ultrasonographic are not yet fulfilled. In 2 cases the prenatal diagnosis of urinary tract malformations was not confirmed by the postnatal evaluation. Our experience shows that the prenatal diagnosis of congenital malformations of urinary tract is particularly useful, even considering the opportunities of perinatal management and postnatal surgical treatment in several cases.

[Role of diagnostic imaging in Rubinstein-Taybi syndrome. Personal experience with 8 cases]. / Ruolo della diagnostica per immagini nella sindrome di Rubinstein-Taybi. Esperienza personale su 8 casi.

Both etiology and pathogenesis of Rubinstein-Taybi syndrome (RTS) are still questionable, even though a genetic factor seems to be certain. A typical face, psychomotor delay, and thumb and halluces abnormalities (big, prevalently short, and often "spoon-like" toes) are the main characteristic patterns of RTS. Eight subjects (4 male and 3 female children aged 26 days-7 years, and a 31-year-old woman, mother of 1 of the affected children) with different signs of RTS were studied over the last 3 years. The results are here reported, with a special emphasis on malformations detected with conventional radiography (Rx), Computerized Tomography (CT), and ultrasound (US). Evaluated parameters were thumbs and halluces (Rx), bone age and skeleton (Rx), cranium (Rx) and encephalon (US, CT), cryptorchidism (US, CT), and urological (Rx, US) and cardiovascular (US) systems. A typical face and psychomotor delay were found in all cases, while thumb and halluces abnormalities were observed only in 6 cases. Among several clinical signs of RTS, we found: severe (less than 3rd centile) bone maturation delay in 4 cases; skull volume reduction (less than 50th centile) in 3 subjects and microcrania in 4; skeletal abnormalities in 7 cases (5 of them positive for bilateral coxofemoral abnormalities); urinary tract (4 cases) and cardiovascular (3 cases) malformations; and cryptorchidism in 3 of 4 males. A case was diagnosed during neonatal period (within the first month of life); it was a rare case associated with a variant form of Dandy-Walker anomaly; semiologic similarities were observed between mother and daughter patients. X-rays, US and CT rarely play an important role in the diagnosis of RTS, considering the several clinical signs, mainly the face, affecting the patients. However, diagnostic imaging techniques help diagnose hidden malformations and confirm and integrate clinical signs.

Kabuki make-up (Niikawa-Kuroki) syndrome: clinical and radiological observations in two Sicilian children.

The Authors describe two patients aged 5 and 8, a female and a male, affected by a condition of polymalformations known as Kabuki make-up or Niikawa-Kuroki syndrome, having a neonatal incidence of 1:32,000 in Japan. There are two hypothesis about the apparent rarity of the syndrome in the rest of the world, including the Asian Continent: the first is that it exists, but is infrequently recognized outside Japan and the second is that it is really more frequent in those parts of the world, where ethnic exchanges are uncommon, as it happens in Japan.

Growth charts of Down syndrome in Sicily: evaluation of 382 children 0-14 years of age.

We present the results of a study performed on a Sicilian population of children with Down syndrome (DS) 0-14 years of age, observed between 1977 and 1988. Data from the present report concern 382 subjects with nonmosaic 21 trisomy, including 239 males (62.6%) and 143 females (37.4%). We excluded all DS children observed in the same period with associated pathology (congenital heart defects, gastrointestinal malformations, malabsorption, hypothyroidism, and thalassemia). Overall, 1,464 measurements were performed of length or height, weight, and head circumference. Means and standard deviation (SD) were calculated for all of these parameters. Our data confirm a trend toward a progressive improvement of growth in children with DS, as shown in other recent reports. The purpose of this study was also to create a "normal growth pattern" useful to evaluate DS children and also to diagnose early pathologic conditions affecting growth, such as autoimmune diseases.