Children and adolescents with sex chromosome trisomies (SCTs) usually show a higher frequency of behavioral problems than typically developing (TD) children. However, little is known about the ...presence of behavioral issues in toddlers with SCT. This study aimed at investigating their behavioral profile in the second year of life and its impact on maternal stress.
Participants were 87 children ranging in age from 18 to 26 months: 63 children with SCTs (all diagnosed prenatally) and 24 TD children. Their psychomotor and language development and their behavioral profile were assessed. In addition, the level of maternal parenting stress was evaluated.
Both psychomotor and language development were significantly lower in children with SCTs than in TD children. Conversely, no significantly greater behavioral problems emerged in children with SCTs. However, a significantly higher level of parenting stress related to a dysfunctional interaction with the child emerged in the mothers of children with SCTs. In this population, maternal stress seemed positively related to their children's emotional problems and pervasive disorders and negatively related to their children's psychomotor and linguistic competence.
Although no significant behavioral issues emerged in the second year of life, the relationships found between children's behavioral profiles and maternal parenting stress highlight the importance of prenatal counseling and support groups for parents of children with SCTs. This might help them recognize the first signs of behavioral problems and become aware of their influence on parenting stress.
The neuropsychological profile associated with sex chromosome trisomies (SCT) is frequently characterised by delays or deficits in linguistic development. Although maternal input could have an ...important role in influencing and shaping the linguistic development of children with SCT, there is a lack of studies in the literature that have investigated its prosodic characteristics. The study aims to analyse the prosodic features of the maternal input addressed to a group of 8-month-old children with SCT and a group of typically developing (TD) peers. Nineteen mother–child dyads with children with SCT and 19 mother–child dyads with TD children participated in the study. Maternal utterances were collected during video-recorded play sessions, and for each dyad, 50 maternal utterances were selected and analysed using the software Praat. The results showed that the maternal input produced by the mothers in the SCT group was characterised by a significantly lower pitch, less marked and modulated melodic contours, and a shorter final syllable duration than the input addressed to TD children. The prosodic features found in the maternal input addressed to children with SCT were not those expected in the maternal input addressed to children at this developmental stage and could create a non-optimal linguistic environment.
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated ...with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.
we report on two patients affected by MRKH syndrome in which array-CGH analysis disclosed an identical deletion spanning 1.5 Mb of genomic DNA at chromosome 17q12. One patient was affected by complete absence of uterus and vagina, with bilaterally normal ovaries, while the other displayed agenesis of the upper part of vagina, right unicornuate uterus, non cavitating rudimentary left horn and bilaterally multicystic kidneys. The deletion encompassed two candidate genes, TCF2 and LHX1. Mutational screening of these genes in a selected group of 20 MRKH females without 17q12 deletion was negative.
Deletion 17q12 is a rare albeit recurrent anomaly mediated by segmental duplications, previously reported in subjects with developmental kidney abnormalities and diabetes. The present two patients expand the clinical spectrum associated with this imbalance and suggest that this region is a candidate locus for a subset of MRKH syndrome individuals, with or without renal defects.
Genomic imprinting is an epigenetic phenomenon restricting gene expression in a manner dependent on parent of origin. Imprinted gene products are critical regulators of growth and development, and ...imprinting disorders are associated with both genetic and epigenetic mutations, including disruption of DNA methylation within the imprinting control regions (ICRs) of these genes. It was recently reported that some patients with imprinting disorders have a more generalised imprinting defect, with hypomethylation at a range of maternally methylated ICRs. We report a cohort of 149 patients with a clinical diagnosis of Beckwith-Wiedemann syndrome (BWS), including 81 with maternal hypomethylation of the KCNQ1OT1 ICR. Methylation analysis of 11 ICRs in these patients showed that hypomethylation affecting multiple imprinted loci was restricted to 17 patients with hypomethylation of the KCNQ1OT1 ICR, and involved only maternally methylated loci. Both partial and complete hypomethylation was demonstrated in these cases, suggesting a possible postzygotic origin of a mosaic imprinting error. Some ICRs, including the PLAGL1 and GNAS/NESPAS ICRs implicated in the aetiology of transient neonatal diabetes and pseudohypoparathyroidism type 1b, respectively, were more frequently affected than others. Although we did not find any evidence for mutation of the candidate gene DNMT3L, these results support the hypotheses that trans-acting factors affect the somatic maintenance of imprinting at multiple maternally methylated loci and that the clinical presentation of these complex cases may reflect the loci and tissues affected with the epigenetic abnormalities.
The Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal ...studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults.
This observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity.
IGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM.
IGM incidence is high in young adults with WS, suggesting the need of early screening and timed intervention. As in classical type 2 diabetes, impaired insulin sensitivity and β-cell dysfunction contribute, in this sequence, to progression to IGM and DM.
Gnathodiaphyseal dysplasia (GDD) is an autosomal dominant syndrome characterized by frequent bone fractures at a young age, bowing of tubular bones and cemento-osseus lesions of the jawbones. ...Anoctamin 5 (ANO5) belongs to the anoctamin protein family that includes calcium-activated chloride channels. However, recent data together with our own experiments reported here add weight to the hypothesis that ANO5 may not function as calcium-activated chloride channel. By sequencing the entire ANO5 gene coding region and untranslated regions in a large Italian GDD family, we found a novel missense mutation causing the p.Thr513Ile substitution. The mutation segregates with the disease in the family and has never been described in any database as a polymorphism. To date, only two mutations on the same cysteine residue at position 356 of ANO5 amino-acid sequence have been described in GDD families. As ANO5 has also been found to be mutated in two different forms of muscular dystrophy, the finding of this third mutation in GDD adds clues to the role of ANO5 in these disorders.
Context: Implementation of pre-conception care units is still very limited in Italy. Nowadays, the population’s awareness of the reproductive risks that can be reduced or prevented is very low. ...Purpose and main findings: We presented a new personalized multidisciplinary model of preconception care aimed at identifying and possibly reducing adverse reproductive events. We analyzed three cohorts of population: couples from the general population, infertile or subfertile couples, and couples with a previous history of adverse reproductive events. The proposal involves a deep investigation regarding family history, the personal histories of both partners, and reproductive history. Principal conclusions: Preconception care is still neglected in Italy and under-evaluated by clinicians involved in natural or in vitro reproduction. Adequate preconception counseling will improve maternal and fetal obstetrical outcomes.
The risk of adverse pregnancy outcomes can be minimized through the adoption of healthy lifestyles before pregnancy by women of childbearing age. Initiatives for promotion of preconception health may ...be difficult to implement. Internet can be used to build tailored health interventions through identification of the public's information needs. To this aim, we developed a semi-automatic web-based system for monitoring Google searches, web pages and activity on social networks, regarding preconception health.
Based on the American College of Obstetricians and Gynecologists guidelines and on the actual search behaviors of Italian Internet users, we defined a set of keywords targeting preconception care topics. Using these keywords, we analyzed the usage of Google search engine and identified web pages containing preconception care recommendations. We also monitored how the selected web pages were shared on social networks. We analyzed discrepancies between searched and published information and the sharing pattern of the topics.
We identified 1,807 Google search queries which generated a total of 1,995,030 searches during the study period. Less than 10% of the reviewed pages contained preconception care information and in 42.8% information was consistent with ACOG guidelines. Facebook was the most used social network for sharing. Nutrition, Chronic Diseases and Infectious Diseases were the most published and searched topics. Regarding Genetic Risk and Folic Acid, a high search volume was not associated to a high web page production, while Medication pages were more frequently published than searched. Vaccinations elicited high sharing although web page production was low; this effect was quite variable in time.
Our study represent a resource to prioritize communication on specific topics on the web, to address misconceptions, and to tailor interventions to specific populations.
Omphalocele is a congenital midline ventral body wall defect that can exist as isolated malformation or as part of a syndrome. It can be considered one of the major and most frequent clinical ...manifestation of Beckwith-Wiedemann Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C mutations. The isolated form of the omphalocele accounts approximately for about the 14% of the total cases and its molecular etiology has never been fully elucidated.
Given the tight relationship with BWS, we hypothesized that the isolated form of the omphalocele could belong to the heterogeneous spectrum of the BWS associated features, representing an endophenotype with a clear genetic connection. We therefore investigated genetic and epigenetic changes affecting BWS imprinted locus at 11p15.5 imprinted region, focusing in particular on the KCNQ1OT1:TSS DMR.
We studied 21 cases of isolated omphalocele detected during pregnancy or at birth and identified the following rare maternally inherited variants: i) the non-coding variant G > A at nucleotide 687 (NR_002728.3) at KCNQ1OT1:TSS-DMR, which alters the methylation pattern of the imprinted allele, in one patient; ii) the deletion c.624-629delGGCCCC at exon 1 of CDKN1C, with unknown clinical significance, in two unrelated cases.
Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could be a susceptibility locus for the isolated omphalocele.
The 2q3 duplication and 4q3 deletion are two distinct conditions with variable phenotypes including developmental delay, intellectual disability, Pierre Robin sequence (PRS), and cardiovascular, ...craniofacial, digital and skeletal anomalies. We describe two cousins, a 37-year-old man (Patient 1) and a 17-year-old girl (Patient 2), with a derivative chromosome leading to a 4q35 deletion-2q35q37 duplication. Conventional karyotype showed in both patients the same rearrangement derived from unbalanced segregation of a parental reciprocal translocation involving the long arms of chromosome 2 and 4. Patient 1's father and Patient 2's mother were identified as the carriers of a balanced translocation t(2;4)(q35;q35). Array-CGH analysis, performed to characterize the rearrangement, documented in both patients the presence of a 26 Mb duplication of the 2q35-q37.3 region of chromosome 2 and a 6.3 Mb deletion of the 4q35.1-q35.2 region of chromosome 4. Both patients showed intellectual disability, minor facial, and digital anomalies, hearing, ocular, and genitourinary abnormalities. The comparison of their features with those of published cases of 2q3 duplication and 4q3 deletion allowed us to further delineate the genotype-phenotype correlation as well as the combined effect of partial 2q duplication and 4q deletion syndromes in adulthood.
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