Sex Chromosome Trisomies Research Articles

Neurodevelopment in Young Children With Sex Chromosome Trisomies Diagnosed Before Birth: A Cluster Analysis Study.

Many studies have investigated the neuropsychological profile of individuals with sex chromosome trisomies (SCTs) and have identified some fragilities in language development within a wide individual variability. However, only a few studies have focused on children in the second year of life (12-24 months), a crucial stage for neurodevelopment. The present study aimed to identify and describe neurodevelopmental patterns in young children with SCTs. Seventy children with SCTs, ranging in age from 14 to 29 months, were administered the Griffiths Mental Development Scales, and their different neurodevelopmental profiles were identified using cluster analysis. Two-step cluster analysis highlighted two profiles of children equally distributed between groups. The two clusters showed a similar pattern but different levels of functioning, with children in Cluster 1 showing a lower performance in all the areas considered than children in Cluster 2. However, in both clusters, all the mean scores were in the normative range, with a significant gap in the linguistic area. Identifying the subgroups of young children with SCTs at higher risk can contribute to developing early monitoring protocols and targeted therapy approaches.

Quantifying the Spectrum of Early Motor and Language Milestones in Sex Chromosome Trisomy.

Sex chromosome trisomy (SCT) is a common chromosomal abnormality associated with increased risks for early developmental delays and neurodevelopmental disorders later in childhood. Our objective was to quantify the spectrum of early developmental milestones in SCT. We hypothesized later milestone achievement in SCT than the general population. Data were collected as part of the eXtraordinarY Babies Study, a prospective natural history of developmental and health trajectories in a prenatally identified sample of infants with SCT. Parent reported, clinician-validated, early motor and language milestones were collected at 2, 6, 12, 18, 24, and 36-months. Age distributions of milestone achievement were compared with normative data. In all SCT conditions, compared with normative data, there was increased variability and a later median age of skill development across multiple gross motor and expressive language milestones. Results also show a significant amount of overlap with the general pediatric population, suggesting that for many children with prenatally identified SCT, early milestones present within, or close to, the expected timeline. As increasing numbers of infants with prenatal SCT diagnoses present at pediatric practices, we provide an evidence-based schedule of milestone achievement in SCT as a tool for pediatricians and families. Detailed data on SCT milestones can support clinical interpretation of milestone achievement. Increased variability and later median age of milestone acquisition in SCT compared to norms support consideration of all infants with SCT as high risk.

Prosody in narratives: An exploratory study with children with sex chromosomes trisomies

Although language delays are common in children with sex chromosome trisomies [SCT], no studies have analysed their prosodic abilities. Considering the importance of prosody in communication, this exploratory study aims to analyse the prosodic features of the narratives of 4-year-old children with SCT.Participants included 22 children with SCT and 22 typically developing [TD] children. The Narrative Competence Task was administered to elicit the child's narrative. Each utterance was prosodically analysed considering pitch and timing variables.Considering pitch, the only difference was the number of movements since the utterances of children with SCT were characterised by a lower speech modulation. However, considering the timing variables, children with SCT produced a faster speech rate and a shorter final syllable duration than TD children.Since both speech modulation and duration measures have important syntactic and pragmatic functions, further investigations should deeply analyse the prosodic skills of children with SCT in interaction with syntax and pragmatics.

Medical Findings in Infants Prenatally Identified with Sex Chromosome Trisomy in Year One of Life.

Sex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification of these conditions, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal features, medical diagnoses, and physical features in infants with prenatal identification of SCT conditions through the first year of life. The eXtraordinarY Babies Study is an ongoing, prospective natural history study of prenatally identified children with SCT conducted by interdisciplinary teams in Colorado and Delaware. Participants were enrolled prior to 12 months of age and had pregnancy, birth, medical histories, and physical exams completed by board-certified pediatricians at 2, 6, and/or 12-month visits. Descriptive statistics were followed by comparisons between SCT groups using t-tests or ANOVA, Fisher exact, and correlations between medical features with alpha of 0.05. Relative risks were calculated compared to general population rates. 327 infants were included in the analysis (XXY=195, XXX=79, XYY=53). Major congenital anomalies were rare (1.7%). Relative risk compared to general population was elevated for breastfeeding difficulties (51.7%;RR 2.7), positional torticollis (28.2%;RR 7.2), eczema (48.0%;RR 3.5), food allergies (19.3%;RR 2.4), constipation requiring intervention (33.9%;RR 7.6), small cardiac septal defects (7.7%;RR 17.2), and structural renal abnormalities (4.4%;RR 9.7). Inpatient hospitalization was required for 12.4%, with 59.5% of hospitalizations attributable to respiratory infections. These findings of medical conditions with a higher prevalence can inform anticipatory guidance and medical management for pediatricians caring for infants with SCT. Medical findings in largest cohort of prenatally identified infants with XXY, Trisomy X, and XYY from birth to 12 months and implications for pediatric care.What's Known on This Subject: One in ∼500 individuals have an extra X or Y chromosome, or sex chromosome trisomy (SCT). Prenatal screening is now routinely identifying SCT, however there are few studies to guide perinatal and infant care for these individuals.What This Study Adds: This prospective observational study presents medical features for 327 infants with prenatally identified SCT from birth through the first year of life. Results identify where proactive screenings and/or interventions may be warranted for infants with SCT.

Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies

ABSTRACT Background Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort. Research design and methods In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated. Results The sensitivity was 97.7% (95%CI, 87.7–99.9), 87.3% (95% CI, 76.5–94.4), 96.1% (95%CI, 86.5–99.5), and 95.7% (95% CI, 78.1–99.9), the PPV was 25.8% (95%CI, 19.2–33.2), 80.9% (95%CI, 69.5–89.4), 79.0% (95%CI, 66.8–88.3), and 53.7% (95%CI, 37.4–69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0–95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all. Conclusions NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

Clinical evaluation of noninvasive prenatal testing for sex chromosome aneuploidies in 9,176 Korean pregnant women: a single-center retrospective study

BackgroundTo evaluate the clinical significance of noninvasive prenatal testing (NIPT) for detecting fetal sex chromosome aneuploidies (SCAs) in Korean pregnant women.MethodsWe retrospectively analyzed NIPT data from 9,176 women with singleton pregnancies referred to the CHA Biotech genome diagnostics center. Cell-free fetal DNA (cffDNA) was extracted from maternal peripheral blood, and high-throughput massively parallel sequencing was conducted. Subsequently, the positive NIPT results for SCA were validated via karyotype and chromosomal microarray analyses.ResultsOverall, 46 cases were SCA positive after NIPT, including 20, 12, 8, and 6 for Turner, triple X, Klinefelter, and Jacob syndromes, respectively. Among 37 women with invasive prenatal diagnosis, 19 had true positive NIPT results. The overall positive predictive value (PPV) of NIPT for detecting SCAs was 51.35%. The PPV was 18.75% for Turner, 88.89% for triple X, 71.43% for Klinefelter, and 60.00% for Jacob’s syndromes. NIPT accuracy for detecting sex chromosome trisomies was higher than that for sex chromosome monosomy (P = 0.002). No significant correlation was observed between fetal SCA incidence and maternal age (P = 0.914), except for the borderline significance of Jacob’s syndrome (P = 0.048). No significant differences were observed when comparing NIPT and karyotyping validation for fetal SCA according to pregnancy characteristics.ConclusionOur data suggest that NIPT can reliably screen for SCAs, and it performed better in predicting sex chromosome trisomies compared with monosomy X. No correlation was observed between maternal age and fetal SCA incidence, and no association was observed between different pregnancy characteristics. The accuracy of these findings requires improvements; however, our study provides an important reference for clinical genetic counseling and further management. Larger scale studies, considering confounding factors, are required for accurate evaluation.

Maternal input to 24-month-old children with sex chromosome trisomies.

Maternal input plays an important role in influencing linguistic development during the first years of life, and it is evident that mothers adapt their language according to their child's characteristics. Recently, it was demonstrated that maternal input addressed to children with sex chromosome trisomies (SCTs) at 8 months of age is prosodically and functionally different from that addressed to typically developing (TD) peers. The study aimed at analysing maternal input at 24 months when the presence of a language delay could be more evident than during the preverbal stage. We were interested in examining if maternal input was influenced by a diagnosis of SCT (by comparing children with SCT and TD children) or by children's linguistic level (by comparing children with weak lexical ability versus children with typical lexical ability regardless of the presence of genetic diagnosis). Forty-four mother-child dyads in which the children had an SCT and 20 mother-child dyads in which the children were TD participated in the study. Of these 64 dyads, 23 children (21 with SCTs and two TD children) formed the group of children with weak lexical ability (children with a vocabulary size lower than 50 words at 24 months). Maternal utterances were collected during one video-recorded play session and were then coded considering both the linguistic and functional features of the input. The results showed that the input addressed to 24-month-old children with SCTs is as rich and complex as that addressed to TD peers. Moreover, no significant differences in the functions expressed by maternal input were found (all ps > 0.05). Comparing the children with weak lexical ability and the children with typical lexical ability in our sample, having a poor vocabulary at 24 months of age showed a significant influence on the maternal input features: the input addressed to children with weak lexical ability was characterised by a higher presence of attention getters (U = 217.00, p = 0.007) and a lower proportion of questions (U = 236.00, p = 0.017) than that of mothers of typically-talking children. At 24 months of age, it seems that the presence of a language delay and not belonging to the clinical group of children with SCTs influences the functional characteristics of the maternal input. It is important to support the parents of children with SCTs during the communication process and later during their child's development, leading them to observe their children's manifested skills rather than looking for possible predicted difficulties. What is already known on the subject Studies in the literature demonstrated how mothers can generally adapt their input to their child's characteristics. To our knowledge, only two recent studies analysed the maternal input addressed to children with SCT at 8 months of age, highlighting significant differences. What this paper adds to existing knowledge The maternal input addressed to children with SCT at 24 months of age is not different from that addressed to TD children. At 24 months of age, the mothers adapt their input to the verbal competence shown by their child (weak lexical ability versus typically-talking), while belonging to the clinical group does not show an influence. What are the potential or actual clinical implications of this work? All the participants of the present study received prenatal diagnosis disclosure by an expert team of professionals, and they were all involved in a longitudinal study aimed at monitoring the children's development and supporting their parents. These results show that giving clear and complete information about possible development paths to parents of children with SCTs during diagnosis disclosure is crucial. Moreover, supporting the parents during the communication process and later during their child's development is fundamental, leading them to observe their children's manifested skills rather than looking for possible predicted difficulties.

Analysis of the Detection Status of Non-Invasive Prenatal Testing in Sex Chromosome Abnormalities

Objective: To analyze the detection efficiency of non-invasive prenatal tests (NIPT) in single fetus sex chromosome abnormalities and explore the application value of NIPT in sex chromosome diseases. Method: A total of 47,770 singleton pregnant women received free NIPT at Dongguan Maternity and Infant Clinic. Pregnant women with NIPT results indicating sex chromosome abnormalities provided informed consent for amniocentesis and subsequent karyotype analysis and/or multiplex ligation probe amplification (MLPA) technology. The study also involved telephone follow-ups on test results and pregnancy outcomes, along with a retrospective analysis of the positive detection rate of sex chromosome abnormalities by NIPT. Results: Among the 47,770 pregnant women, NIPT identified sex chromosome abnormalities in 158 cases, resulting in a detection rate of 0.33%. Of these cases, 113 pregnant women opted for amniocentesis, while 36 declined. One newborn, whose parents refused puncture, was later diagnosed with cryptorchidism. 8 cases failed to follow up. Among the 113 cases undergoing amniocentesis, 55 were diagnosed with sex chromosome abnormalities. These included 7 cases of X monosomy, 24 cases of sex chromosome trisomy (14 cases of Klinefelter syndrome; 5 cases of Jacobs syndrome; 5 cases of trisomy X), and 24 cases with sex chromosome microdeletions and microduplications. Meanwhile, 58 cases had no abnormalities. The overall positive predictive value (PPV) of NIPT testing for sex chromosome abnormalities was 48.67%, with specific PPVs for monosomy X, Klinefelter syndrome, Jacobs syndrome, trisomy X, and sex chromosome microdeletions and microduplications being 6.19%, 12.39%, 4.42%, 4.42%, and 21.24% respectively. Conclusion: NIPT demonstrates high detection efficiency in sex chromosome diseases. However, the efficiency varies significantly across different chromosomal abnormalities. Pregnant women with NIPT results indicating sex chromosome abnormalities should undergo amniocentesis for karyotype analysis and MLPA.

Social Communication in Young Children With Sex Chromosome Trisomy (XXY, XXX, XYY): A Study With Eye Tracking and Heart Rate Measures.

Children with sex chromosome trisomy (SCT) have an increased risk for suboptimal development. Difficulties with language are frequently reported, start from a very young age, and encompass various domains. This cross-sectional study examined social orientation with eye tracking and physiological arousal responses to gain more knowledge on how children perceive and respond to communicative bids and evaluated the associations between social orientation and language outcomes, concurrently and 1 year later. In total, 107 children with SCT (33 XXX, 50 XXY, and 24 XYY) and 102 controls (58 girls and 44 boys) aged between 1 and 7years were included. Assessments took place in the USA and Western Europe. A communicative bids eye tracking paradigm, physiological arousal measures, and receptive and expressive language outcomes were used. Compared to controls, children with SCT showed reduced attention to the face and eyes of the on-screen interaction partner and reduced physiological arousal sensitivity in response to direct versus averted gaze. In addition, social orientation to the mouth was related to concurrent receptive and expressive language abilities in 1-year-old children with SCT. Children with SCT may experience difficulties with social communication that extend past the well-recognized risk for early language delays. These difficulties may underlie social-behavioral problems that have been described in the SCT population and are an important target for early monitoring and support.

Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX, and 45,X/47,XXX.

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis is on potential fertility. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5 % of females with the Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population, but not nearly so severe as those with 47,XXY karyotype. Assisted reproductive technology, especially micro-TESE has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3-D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of prenatal cfDNA screening for sex chromosomes

PurposeThe aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. MethodsThis was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. ResultsA total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. ConclusionScreening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.

(Not) getting what you want: frustration and emotion regulation in children with sex chromosome trisomies.

The presence of an additional X or Y chromosome (sex chromosome trisomies, SCT) is associated with an increased risk for neurodevelopmental difficulties, including socio-emotional problems, across the life span. Studying emotion regulation in young children with SCT could signal deviations in emotional development that serve as risk markers to guide clinical care. This study explored the presence and variety of emotion regulation strategies in 75 SCT children and 81 population-based controls, aged 1-7 years, during a frustration-inducing event in which physiological (heart rate) and observational data (behavioral responses) were collected. Children with SCT were equally physiologically aroused by the event as compared to controls. However, they showed more emotion regulation difficulties in terms of behavior compared to controls that were not explicable in terms of differences in general intellectual functioning. Specifically, they had a more limited range of behavioral alternatives and tended to rely longer on inefficient strategies with increasing age. The field of practice should be made aware of these early risk findings regarding emotion regulation in SCT, which may potentially lay the foundation for later socio-emotional problems, given the significant impact of emotion regulation on child and adult mental health outcomes. The current results may help to design tailored interventions to reduce the impact of the additional sex chromosome on adaptive functioning, psychopathology, and quality of life.

Neurocognitive and behavioral development in young children (1-7 years) with sex chromosome trisomy.

Investigating sex chromosome trisomies (SCTs) may help in understanding neurodevelopmental pathways underlying the risk for neurobehavioral problems and psychopathology. Knowledge about the neurobehavioral phenotype is needed to improve clinical care and early intervention for children with SCT. This is especially relevant considering the increasing number of early diagnosed children with the recent introduction of noninvasive prenatal screening. The TRIXY Early Childhood Study is a longitudinal study designed to identify early neurodevelopmental risks in children with SCT, aged 1-7 years. This review summarizes the results from the TRIXY Early Childhood Study, focusing on early behavioral symptoms in areas of autism spectrum disorder, attention-deficit hyperactivity disorder, and communication disorders, and underlying neurocognitive mechanisms in domains of language, emotion regulation, executive functioning, and social cognition. Behavioral symptoms were assessed through structured behavior observation and parental questionnaires. Neurocognition was measured using performance tests, eyetracking, and psychophysiological measures of arousal. In total, 209 children aged 1-7 years were included: 107 children with SCT (33 XXX, 50 XXY, and 24 XYY) and 102 age-matched population controls. Study outcomes showed early behavioral symptoms in young children with SCT, and neurocognitive vulnerabilities, already from an early age onward. Neurobehavioral and neurocognitive difficulties tended to become more pronounced with increasing age and were rather robust, independent of specific karyotype, pre/postnatal diagnosis, or ascertainment strategy. A more longitudinal perspective on neurodevelopmental 'at-risk' pathways is warranted, also including studies assessing the effectiveness of targeted early interventions. Neurocognitive markers that signal differences in neurodevelopment may prove to be helpful in this. Focusing on early development of language, social cognition, emotion regulation, and executive functioning may help in uncovering early essential mechanisms of (later) neurobehavioral outcome, allowing for more targeted support and early intervention.

A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy.

All eutherian mammals show chromosomal sex determination with contrasting sex chromosome dosages (SCDs) between males (XY) and females (XX). Studies in transgenic mice and humans with sex chromosome trisomy (SCT) have revealed direct SCD effects on regional mammalian brain anatomy, but we lack a formal test for cross-species conservation of these effects. Here, we develop a harmonized framework for comparative structural neuroimaging and apply this to systematically profile SCD effects on regional brain anatomy in both humans and mice by contrasting groups with SCT (XXY and XYY) versus XY controls. Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences. However, mice do show subtle effects of XXY and XYY on regional volume, although there is not a general spatial convergence in these effects within mice or between species. Notwithstanding this general lack of conservation in SCT effects, we detect several brain regions that show overlapping effects of XXY and XYY both within and between species (cerebellar, parietal, and orbitofrontal cortex), thereby nominating high priority targets for future translational dissection of SCD effects on the mammalian brain. Our study introduces a generalizable framework for comparative neuroimaging in humans and mice and applies this to achieve a cross-species comparison of SCD effects on the mammalian brain through the lens of SCT.SIGNIFICANCE STATEMENT Sex chromosome dosage (SCD) affects neuroanatomy and risk for psychopathology in humans. Performing mechanistic studies in the human brain is challenging but possible in mouse models. Here, we develop a framework for cross-species neuroimaging analysis and use this to show that an added X- or Y-chromosome significantly alters human brain anatomy but has muted effects in the mouse brain. However, we do find evidence for conserved cross-species impact of an added chromosome in the fronto-parietal cortices and cerebellum, which point to regions for future mechanistic dissection of sex chromosome dosage effects on brain development.

Speech Sound Development in 18-Month-Old Children With Sex Chromosome Trisomies.

This study aimed to describe speech sound development in a group of 18-month-old children with sex chromosome trisomies (SCTs), compared with a group of typically developing (TD) peers. Concurrent and longitudinal relationships between speech sound abilities and lexical development were examined. A group of 76 children aged 18 months, 38 children prenatally diagnosed with SCTs (12 with XXY, 12 with XYY, and 14 with XXX) and 38 TD children, participated in the study. From video recordings of semistructured naturalistic parent-child play sessions, quantitative and qualitative measures of speech sound development were collected (e.g., the number of consonants, type and place of articulation, and syllable structures used), and group differences were observed. The relationships between the number of consonants produced and vocabulary size at 18 and 24 months were assessed. At 18 months, children with SCTs used a significantly lower number of consonants than TD children. Qualitatively, children with SCTs used significantly fewer articulatory complex consonants (fricative/affricates) and a more restricted inventory of syllable structures. The number of consonants used was significantly correlated with lexical development at 18 months. Moreover, in the SCTs group (but not in the TD group), the children with lower speech sound development at 18 months showed a significantly smaller vocabulary growth between 18 and 24 months than those with higher speech-sound development. Toddlers with SCTs showed a significantly delayed speech sound development pattern rather than an atypical one. Children with SCTs with low speech sound development also showed lower vocabulary growth between 18 and 24 months of age. These results can be clinically relevant for follow-up and treatment planning for children with SCTs.

P195: The eXtraordinarY Babies Study: Prevalence of congenital anomalies and medical conditions among neonates and infants with sex chromosome trisomies (SCT)*

P195: The eXtraordinarY Babies Study: Prevalence of congenital anomalies and medical conditions among neonates and infants with sex chromosome trisomies (SCT)*

P323: Creating developmental growth curves and milestone charts for infants with sex chromosome trisomy using data from the eXtraordinarY Babies Study*

P323: Creating developmental growth curves and milestone charts for infants with sex chromosome trisomy using data from the eXtraordinarY Babies Study*

Clinical, Cognitive and Neurodevelopmental Profile in Tetrasomies and Pentasomies: A Systematic Review.

Background: Sex chromosome aneuploidies (SCAs) are a group of disorders characterised by an abnormal number of sex chromosomes. Collective prevalence rate of SCAs is estimated to be around 1 in 400-500 live births; sex chromosome trisomies (e.g., XXX, XXY, XYY) are most frequent, while tetra- and pentasomies (e.g., XXXX, XXXXX, XXXY, XXXXY) are rarer, and the most common is 48, XXYY syndrome. The presence of additional X and/or Y chromosomes is believed to cause neurodevelopmental differences, with increased risk for developmental delays, language-based learning disabilities, cognitive impairments, executive dysfunction, and behavioural and psychological disorders. Aim of the Study: Our review has the purpose of analysing the neurocognitive, linguistical and behavioural profile of patients affected by sex chromosomes supernumerary aneuploidies (tetrasomy and pentasomy) to better understand the specific areas of weakness, in order to provide specific rehabilitation therapy. Methods: The literature search was performed by two authors independently. We used MEDLINE, PubMed, and PsycINFO search engines to identify sources of interest, without year or language restrictions. At the end of an accurate selection, 16 articles fulfilled the inclusion and exclusion criteria. Results and Conclusions: International literature has described single aspects of the neuropsychological profile of 48, XXYY and 49, XXXXY patients. In 48, XXYY patients, various degrees of psychosocial/executive functioning issues have been reported and there is an increased frequency of behavioural problems in childhood. Developmental delay and behavioural problems are the most common presenting problems, even if anxiety, depression and oppositional defiant disorder are also reported. They also show generalized difficulties with socialization and communication. Cognitive abilities are lower in measures of verbal IQ than in measures of performance IQ. Visuospatial skills are a relative strength compared to verbal skills. In patients with 49, XXXXY, both intellectual and adaptive functioning skills fall into the disability range, with better non-verbal cognitive performance. Speech and language testing reveals more deficits in expressive language than receptive language and comprehension. Anxiety, thought problems, internalizing and externalizing problems, and deficits in social cognition and communication are reported. Behavioural symptoms lessen from school age to adolescence, with the exception of thought problems and anxiety. Individuals affected by sex chromosome aneuploidies show testosterone deficiency, microorchidism, lack of pubertal progression and infertility. Hormone replacement therapy (HRT) is usually recommended for these patients: different studies have found that testosterone-based HRT benefit a wide range of areas initiated in these disorders, affecting not only neuromotor, cognitive and behavioural profile but also structural anomalies of the brain (i.e., increase of volume of grey temporal lobe matter). In conclusion, further studies are needed to better understand the neuropsychological profile with a complete evaluation, including neurocognitive and psychosocial aspects and to establish the real impact of HRT on improving the cognitive and behavioural profile of these patients.

Short report. Narrative competence in Italian preschool children with sex chromosome trisomies

BackgroundThe neuropsychological profile of children with sex chromosome trisomies [SCTs] is frequently characterised by delays and impairments in language development. However, no studies so far have specifically investigated their narrative competence. AimsThe aim of the study was to analyse the oral narrative competence of preschool children with SCTs due to the importance of this skill for language development and learning abilities. Methods and proceduresParticipants were 34 Italian children with SCTs one-to-one matched by age and sex to typically developing [TD] children. A storytelling task, the Narrative Competence Task, was used to assess the macrostructural and microstructural features of the children's narratives. Outcomes and resultsChildren with SCTs showed significantly lower scores than TD peers in all the narrative indices considered, except for mental state lexicon and story length in words. Conclusions and implicationsThe problems found in narrative competence confirmed the existence of difficulties in the language development of children with SCTs. Narrative difficulties could affect these children's future learning skills and academic achievements.