Before Is Better: Innovative Multidisciplinary Preconception Care in Different Clinical Contexts.

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.

Language Development in the Second Year of Life: The Case of Children with Sex Chromosome Trisomies Diagnosed before Birth.

Many individual factors, such as early communicative skills, could play a role in explaining later linguistic outcomes. The detection of predictive variables is fundamental to identifying early the children who need intervention. The present study focuses on children with sex chromosome trisomies (SCTs), genetic conditions with an increased risk of developing language delays or impairments. The aims are to analyse their communicative skills at 18 months of age, and identify significant predictors of their later vocabulary size. Participants were 76 18-month-old children (38 with SCTs, and 38 typically-developing (TD) children). Their communicative skills were assessed during a parent-child play session, and parents filled in a report on their vocabulary development at 18 and 24 months. Children with SCTs showed significantly poorer linguistic skills at 18 months in both preverbal (babbling and gestures) and verbal abilities. A high percentage (nearly 70%) of toddlers with SCTs were late-talking children at 24 months, and those toddlers showed a lower frequency of babbling utterances at 18 months. Early lexical skills, children's developmental quotient, and being part of the group of toddlers with SCTs were significant predictors of children's vocabulary size six months later. These variables should be considered when assessing the linguistic competence of a child with SCTs to detect possible early risk factors of future language impairment.

Language Development in Sex Chromosome Trisomies: Developmental Profiles at 2 and 4 Years of Age, and Predictive Measures.

PURPOSE: Describing language development in children with sex chromosome trisomies (SCT) and testing the predictive value of early language measures on later outcomes. METHOD: Thirteen children with SCT were followed longitudinally. Their developmental profile was assessed, with particular attention to language, at 2 and 4 years. The predictive value of direct (spontaneous speech analysis) and indirect (communicative development inventory) language measures at 2 on performances at 4 was tested. RESULTS: Language performances at both ages were lower than non-verbal development. At 2, more than 50% of the group produced less than 50 words. At 4, impaired performances were observed in speech sound development and expressive morpho-syntax. Direct measures of Pre-syntactic development predicted later global language outcomes and Sentence Repetition. The number of consonants used at 2 was significantly related to Nonword Repetition at 4. CONCLUSIONS: The study highlights the importance of early detection and careful follow-up for children with SCT.

Children's Behavior and Maternal Parenting Stress in Young Children With Sex Chromosome Trisomies.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Family burden of children suffering from epidermolysis bullosa.

BACKGROUND: Living with a rare disease has profound effects on the patient's life and that of their entire family, with practical and psychosocial consequences. This is particularly true when the patient is a child. The principal aim of this study was to measure the family burden in Epidermolysis Bullosa (EB). The secondary endpoint was to evaluate the possible correlation between family burden and the severity of EB. METHODS: A sample of 50 families with one or two children affected by EB were recruited between January 2016 and February 2017 to answer a 20-item questionnaire - the EB Burden of Disease (EB-BoD) - developed and validated to assess the family burden of children with EB. RESULTS: The presence of a child with EB may have profound negative implications on several different areas of daily life. In particular, the results demonstrate important differences between the different subtypes of epidermolysis bullosa regarding most of the categories considered by the questionnaire. For three categories out of four (family life, child's life, economic and social impact), a higher score is observed for children with the more debilitating forms of EB: recessive dystrophic EB (RDEB) and junctional EB (JEB). CONCLUSIONS: It is important to work with patients and their families to identify and strengthen adaptive and coping behaviors. That is possible only through the synergistic working of a multidisciplinary team made up of experienced doctors, psychologists, and social workers while in contact with patient Associations.

Maternal input to children with sex chromosome trisomies.

BACKGROUND: Although language difficulties are one of the most distinctive characteristics of the neuropsychological profile of children with sex chromosome trisomies (SCT), the analysis of the maternal input addressed to them is a neglected topic. AIMS: The present study aims to analyse the lexical, morphosyntactic, and functional features of the input addressed to children with SCT comparing them with those of the input directed to typically developing children (TD). METHODS & PROCEDURES: Participants were 38 mothers and their 8-month-old children, 19 with SCT and 19 TD children. Maternal utterances, collected during video-recorded play sessions, have been transcribed and coded. OUTCOMES & RESULTS: No significant differences between groups have been found in the lexical and syntactic characteristics of maternal input. However, considering the input functional features, the proportion of directives and questions was significantly higher in the maternal input addressed to children with SCT than in the input addressed to TD children whereas the opposite pattern was found in the proportion of affect-salient speech. CONCLUSIONS & IMPLICATIONS: The awareness of a possible delay in their children's language development could influence the way the mothers speak to them. In particular, the functional features of maternal input could be affected. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development. What this paper adds What is already known on the subject Studies in the literature identified a high percentage of language delays or impairments in children with SCT. To date, according to our knowledge, there are no studies that analyse the linguistic input addressed to these children. What this study adds The lexical and syntactic features of maternal input addressed to 8-month-old children with SCT are adequate to the children's communicative skills. However, the mothers of children with SCT seem to provide additional scaffolding in their verbal input, using a lower proportion of affect-salient speech and a higher proportion of questions. In addition, a higher proportion of directives suggests the use of a more demanding style. Clinical implications of this study The awareness of possible language delays could influence the functional features of input leading mothers to use a more supportive and demanding input. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development.

Klinefelter Syndrome in preschool children: the importance of an early multidisciplinary approach for patients and families.

BACKGROUND: The aim of this study is twofolded: to present a multi-disciplinary and multi-centric approach in the early care of patients with Klinefelter Syndrome (KS) and their families and to increase the knowledge about the behavioral phenotype of preschool boys with KS. METHODS: Fifteen boys (mean age 2 years and 7 months) who had been diagnosed prenatally were evaluated in the areas of adaptive skills, developmental level, language, and behavior. Besides offering information about their child, both parents of each couple were asked to describe their feelings at the time of the prenatal diagnosis and at the time of the study. RESULTS: The behavioral phenotype of the boys of our sample was characterized by a mean Developmental Quotient of 95 (in the normal range) but by low scores in the domain of communication, particularly in the area of expressive language. Behavioral problems were observed in some of the children, and the parents reported significant levels of distress related to their relationship with the child. All parents recalled feeling very anxious when the diagnosis was given, but nine of them (75%) said their concern diminished after receiving genetic counselling. CONCLUSIONS: A multi-disciplinary model is essential in the care of 47,XXY boys and in the assistance to their families, in order both to facilitate the children's growth and offer to the parents updated clinical and psychosocial information about the Klinefelter Syndrome and support.

Early communicative skills of children with Klinefelter syndrome.

Many studies reported the presence of language impairments in children and adolescents with Klinefelter syndrome (KS). However, the first stage of their language development has been scarcely studied. The present study aimed to describe the spontaneous communicative production of 18-month-old children with KS, in comparison with that of typically developing (TD) male peers, aiming to verify the existence of different early communicative skills in both vocal and gestural modality and to identify the presence of possible associations with their later vocabulary size. Children with KS showed a lower competence in both lexical skills and emergent syntactic abilities than TD peers. No significant differences were found in gesture production. Considering the possibility of identifying an association between early communicative skills and later vocabulary size, the vocal production of TD children appeared to be significantly related to their later lexical skills; whereas, the number of gestures produced by children with KS appeared to be related to their later lexical abilities. The early detection of language risk factors will allow early intervention and careful monitoring of these children's communicative development.

Vocal and gestural productions of 24-month-old children with sex chromosome trisomies.

BACKGROUND: Children with sex chromosome trisomies (SCT) frequently show problems in language development. However, a clear description of the communicative patterns of these children is still lacking. AIMS: To describe the first stages of language development in children with SCT in comparison with those in typically developing (TD) children. The purpose was to verify the existence of possible differences in communicative skills (in both vocal and gestural modality) and identify the presence of possible early predictors (i.e., low vocabulary size and low gesture production) of later language impairment in children with SCT. METHODS & PROCEDURES: Fifteen 24-month-old children with SCT (eight males with Klinefelter syndrome (KS) and seven females with triple X syndrome (TX)) and fifteen 24-month-old TD children (eight males and seven females) participated in the study. Their spontaneous communicative productions were assessed during a semi-structured play session in interaction with a parent. In addition, their vocabulary size was assessed using a parental report (the Italian version of the MacArthur Communicative Development Inventories). OUTCOMES & RESULTS: With regards to their vocabulary size, 60% of children with SCT (75% of children with KS and 43% of children with TX) were at risk for language impairments (i.e., they had a vocabulary size smaller than 50 words). In addition, TD children showed better lexical and syntactic skills than children with SCT in their spontaneous communicative productions. However, the production of communicative gestures was higher in children with SCT than in TD children. Boys with KS appeared to differ from TD males in more aspects of communication than girls with TX differed from TD females. CONCLUSIONS & IMPLICATIONS: The study showed the importance of early detection of language risk factors in children with SCT, while also considering the use of compensatory strategies (e.g., the use of communicative gestures).

Familial Duplication/Deletion of 1q42.13q43 as Meiotic Consequence of an Intrachromosomal Insertion in Chromosome 1.

Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date. The imbalances described are usually the result of inherited translocations with other chromosomes. Moreover, few cases of both inter- and intrachromosomal deletions/duplications detected cytogenetically have been described. We report the molecular cytogenetic characterization of an inverted insertion involving the region 1q42.13q43 and segregating in 2 generations of a family. The deletion and the duplication of the same segment were detected in 2 affected family members. SNP array analysis showed the familial origin of the deletion/duplication due to the occurrence of a crossing-over during meiosis. Our report underlines the importance of determining the correct origin of chromosomal aberrations using different molecular cytogenetic tests in order to provide a good estimation of the reproductive risk for the members of the family.

STAR syndrome plus: The first description of a female patient with the lethal form.

The STAR syndrome is a rare X-linked dominant developmental disorder caused by point mutations in the single FAM58A gene or deletions involving FAM58A and its flanking genes. The STAR phenotype is characterized by a rather homogeneous constellation of facial dysmorphisms and malformations summarized by its acronym, Syndactyly, Telecanthus, Anogenital, and Renal malformations. Here we describe a female patient with STAR syndrome and a 130 kb deletion at Xq28, including the FAM58A gene. She presented with cleft lip palate, omphalocele, and cerebral malformations not previously considered part of the phenotypic spectrum of this syndrome. She died at 6 weeks from respiratory failure.

Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could be a susceptibility locus for the isolated omphalocele.

Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five-year follow-up cohort study.

OBJECTIVE: 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 ß-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 ß-cell dysfunction contribute, in this sequence, to progression to IGM and DM.

Why women do not ask for information on preconception health? A qualitative study.

BACKGROUND: Preconception care involves health promotion to reduce risk factors that might affect women and couples of childbearing age. The risk factors of adverse reproductive outcomes include recognized genetic diseases in the family or the individual, previous congenital diseases, miscarriage, prematurity, fetal growth restriction, infertility, chronic maternal diseases, lifestyle, and occupational or environmental factors. Effective preconception care involves a range of preventive, therapeutic and behavioural interventions. Although in Italy there are national preconception care recommendations concerning the general population, they are usually encouraged informally and only for single risk factors. At present there is increasing interest in offering a global intervention in this field. The aim of this study was to investigate attitudes and behaviours of Italian women of childbearing age and healthcare professionals regarding preconception health. METHODS: We conducted a qualitative study among women of childbearing age and healthcare professionals between February 2014 and February 2015. Five focus groups were held: 2 with non-pregnant women aged 22 to 44 years and 3 with healthcare professionals. Discussion topics included women's questions about preconception health, worries and barriers regarding preconception care interventions, attitudes and behaviours of women and healthcare professionals towards preconception health, women's information sources. In the analysis of the focus groups priority was given to what was said by the women, supplemented by information from the healthcare professionals' focus groups. RESULTS: Fourteen women of childbearing age (8 nulliparae and 6 multiparae) and 12 healthcare professionals (3 nurses, 4 midwives, 5 doctors) participated in the focus groups. The results indicate the presence of many barriers and a lack of awareness of preconception health relating to women, healthcare professionals and policies. Women's knowledge and attitudes towards primary preconception care information are described. The main reference source of information in this field for Italian women seems to be their obstetric-gynaecologist. CONCLUSIONS: The study indicates that several barriers influence preconception care in Italy. Moreover, a lack of awareness of preconception health and care among Italian women of childbearing age and healthcare professionals emerges. The findings might contribute to strategies for the implementation of preconception care guidelines.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome and it is usually diagnosed postnatally, on the basis of phenotype. Prenatal ultrasonography may show fetal alterations, but they are not pathognomonic and most of them are frequently detectable only from the 20th week of gestation. Nevertheless, early diagnosis is important to avoid neonatal complications and make timely and informed decisions about the pregnancy. We report on four fetuses from two unrelated families, in whom the application of whole exome sequencing and array-CGH allowed the identification of GPC3 alterations causing SGBS. The careful follow up of pregnancies and more sophisticated analysis of ultrasound findings led to the identification of early prenatal alterations, which will improve the antenatal diagnosis of SGBS. © 2016 Wiley Periodicals, Inc.

Daily life changes and adaptations investigated in 154 families with a child suffering from a rare disability at a public centre for rare diseases in Northern Italy.

BACKGROUND: Living with a disabled child has profound effects on the entire family. With a prevalence of developmental disabilities around 2,5 %, there is a considerable need to promote improvements in the health care system. Little is known about changes and adaptations in the lives of affected families and this paucity of information hinders the improvement of services. This study sought to explore the needs and changes in the everyday life of families with children suffering from rare diseases of varying severity, with and without mental disability. The aim was to measure the socio-demographic characteristics, health care problems and living conditions of a large cohort of families with an affected member. METHODS: A sample of 154 families was recruited between September 2011 and April 2013 to respond to a 136 item questionnaire that explored different areas of concern (diagnosis and follow-up of clinical specialists, relationship with pediatrician, rehabilitation, school, work, institutional and/or private support, child care needs and family relationships). RESULTS: All parents answered the questionnaire. They were satisfied with the services provided in particular for diagnosis and follow-up, relationships with the family pediatrician, rehabilitation services and school, regardless of the severity of condition, presence of intellectual disability (ID) or absence of diagnosis. Negative scores were reported for institutional and/or private support and family relationships in severe conditions. CONCLUSIONS: The Health Care System should maintain a family-centered care and a multi-agency working, improving quality of life of families with disabled child to allow adaptation. At present these services are uncoordinated and financial support is poor, resulting in a heavy burden for these families.

Prenatal ultrasound factors and genetic disorders in pregnancies complicated by polyhydramnios.

OBJECTIVE: The objective of the study is to examine the incidence of chromosomal or genetic abnormalities in pregnancies complicated by polyhydramnios and to assess the value of prenatal ultrasound findings in the prediction of cases associated with such disorders. METHODS: We searched the prenatal records of all patients delivered in our hospital with a diagnosis of polyhydramnios during pregnancy. For each case, maternal characteristics, ultrasound findings, and genetic testing results were recorded. A postnatal follow-up program of at least 6 months, including a clinical assessment by a clinical geneticist, was carried out in all cases. RESULTS: On a total of 195 cases, genetic testing and clinical examination identified a chromosomal or genetic disease in 26 (13.3%) cases. Multivariate analysis demonstrated that significant predictors of a genetic disorder were a deepest vertical pocket of amniotic fluid of ≥13.0 cm (OR 4.306, 95%CI: 1.535-12.079) and reduced fetal movements (OR 25.084, 95%CI: 4.577-137.461), but not the presence of a structural defect. CONCLUSION: A postnatal clinical follow-up program can reveal chromosomal or genetic disorders in about 13% of neonates with a prenatal diagnosis of polyhydramnios. The severity of polyhydramnios and the reduction of fetal movements are independently associated with the presence of such diseases. © 2016 John Wiley & Sons, Ltd.