Enlarged cavum septum pellucidum and small thymus as markers for 22q11.2 deletion syndrome.

BACKGROUND: Enlarged cavum septum pellucidum (CSP) and hypoplastic thymus are proposed extra-cardiac fetal markers for 22q11.2 deletion syndrome. We sought to determine if they were part of the fetal phenotype of our cohort of fetuses with 22q11.2 deletion syndrome. METHODS: Case-control study of fetuses evaluated from 2016 to 2022. The study group included fetuses with laboratory confirmation of 22q11.2 deletion syndrome. The control group included pregnancies with conotruncal cardiac anomalies with normal microarray as well as structurally normal fetuses with normal microarray. The CSP and thymus were routinely measured during anatomical ultrasound in all patients at their initial visit at 27.1 ± 4.7 weeks. The CSP and thymus measurements were classified as abnormal if they were >95% or <5% for gestational age, respectively. The groups were compared using analysis of variance or Kruskal-Wallis for continuous variables and Fisher's exact test for categorical variables. Logistic regression was performed, and a Receiver Operating Characteristic (ROC) curve was constructed. RESULTS: We identified 47 fetuses with 22q11.2 deletion syndrome and compared them to 47 fetuses with conotruncal anomalies and normal microarray and 47 structurally normal fetuses with normal microarray. 51% (24/47) of fetuses with 22q11.2 deletion syndrome had an enlarged CSP compared to 6% (3/47) of fetuses with a conotruncal anomaly and normal microarray and none of the structurally normal fetuses (p < 0.001). Of the fetuses with 22q11.2 deletion syndrome, 83% (39/47) had a hypoplastic or absent thymus compared to 9% (4/47) of the fetuses with a conotruncal anomaly and normal microarray and none of the structurally normal fetuses (p < 0.001). 87% (41/47) of the fetuses with 22q11.2 deletion syndrome had conotruncal cardiac anomalies. Logistic regression revealed that both enlarged CSP and hypoplastic/absent thymus were associated with 22q11.2 deletion syndrome. The area under the ROC curve for the two markers was 0.94. CONCLUSION: An enlarged CSP and hypoplastic/absent thymus appear to be part of the fetal phenotype of 22q11.2 deletion syndrome. These markers are associated with conotruncal anomalies in the setting of 22q11.2 deletion syndrome but not in normal controls or fetuses with conotruncal defects and normal microarrays.

Paid summer undergraduate internships are one strategy to increase diversity in genetic counseling.

The genetic counseling profession has attempted to enhance the diversity of its workforce since its inception but does not yet reflect the demographics of the United States. One barrier to entry into genetic counseling programs may be the ability to gain exposure to the profession prior to applying for entry. Many applicants participate in unpaid shadowing experiences, which could be a limitation to students from underrepresented backgrounds who may be less familiar with the field or who cannot forgo a salary. To address this concern, the University of Pennsylvania Master of Science in Genetic Counseling Program developed a six-week, paid summer internship designed for undergraduates interested in genetic counseling and from underrepresented backgrounds in the field. Students were recruited via social media and word of mouth. Three undergraduates participated in the first year and four in the second year. Participants received lectures on basic topics in genetics and medical genetics, engaged in workshops and panel discussions, attended rounds and case conferences, interacted with genetic counseling mentors, and were able to shadow genetic counselors in the clinic. Benefits to the interns included enhanced appreciation for the field, development of connections with practicing genetic counselors, and development of connections with each other. The program received positive and constructive feedback and has been continued for future summers.

Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders.

PURPOSE: Pathogenic variants in SCN2A cause a wide range of neurodevelopmental phenotypes. Reports of genotype-phenotype correlations are often anecdotal, and the available phenotypic data have not been systematically analyzed. METHODS: We extracted phenotypic information from primary descriptions of SCN2A-related disorders in the literature between 2001 and 2019, which we coded in Human Phenotype Ontology (HPO) terms. With higher-level phenotype terms inferred by the HPO structure, we assessed the frequencies of clinical features and investigated the association of these features with variant classes and locations within the NaV1.2 protein. RESULTS: We identified 413 unrelated individuals and derived a total of 10,860 HPO terms with 562 unique terms. Protein-truncating variants were associated with autism and behavioral abnormalities. Missense variants were associated with neonatal onset, epileptic spasms, and seizures, regardless of type. Phenotypic similarity was identified in 8/62 recurrent SCN2A variants. Three independent principal components accounted for 33% of the phenotypic variance, allowing for separation of gain-of-function versus loss-of-function variants with good performance. CONCLUSION: Our work shows that translating clinical features into a computable format using a standardized language allows for quantitative phenotype analysis, mapping the phenotypic landscape of SCN2A-related disorders in unprecedented detail and revealing genotype-phenotype correlations along a multidimensional spectrum.

Have You Ever Googled a Patient or Been Friended by a Patient? Social Media Intersects the Practice of Genetic Counseling.

Patients and healthcare providers are becoming increasingly connected via social media, bringing new opportunities and challenges. Direct connection can occur between patients and providers using online tools such as Facebook and LinkedIn. In addition, providers can gather information about patients using a search engine such as Google, referred to as patient-targeted Googling (PTG). An online 54-item survey was used to gain information on (1) how and to what extent genetic counseling students and genetic counselors connect directly with patients via social media sites, and (2) gather information on providers using PTG. Four hundred genetic counseling students and genetic counselors participated in the survey. The majority of respondents (88.9%; n = 344/387) find it is never or rarely acceptable to interact with current patients via social media sites; however, 27.7% (n = 110/397) have visited a patient's social media site. Gathering information for patient care was the most commonly reported reason (76.8%; n = 43/56). Thirty-three percent (n = 130/394) have considered searching online or actually searched online for information about a patient. Curiosity was the most common reason (92.7%; n = 114/123); although, respondents also used PTG to obtain contact information and to prepare for patient sessions. Our study supports the need for development and dissemination of professional guidelines to serve as a valuable resource for practicing genetic counselors and genetic counseling training programs.

Maternal communicative behaviours and interaction quality as predictors of language development: findings from a community-based study of slow-to-talk toddlers.

BACKGROUND: Identifying risk and protective factors for language development informs interventions for children with developmental language disorder (DLD). Maternal responsive and intrusive communicative behaviours are associated with language development. Mother-child interaction quality may influence how children use these behaviours in language learning. AIMS: To identify (1) communicative behaviours and interaction quality associated with language outcomes; (2) whether the association between a maternal intrusive behaviour (directive) and child language scores changed alongside a maternal responsive behaviour (expansion); and (3) whether interaction quality modified these associations. METHODS & PROCEDURES: Language skills were assessed at 24, 36 and 48 months in 197 community-recruited children who were slow to talk at 18 months. Mothers and 24-month-olds were video-recorded playing at home. Maternal praise, missed opportunities, and successful and unsuccessful directives (i.e., whether followed by the child) were coded during a 10-min segment. Interaction quality was rated using a seven-point fluency and connectedness (FC) scale, during a 5-min segment. Linear regressions examined associations between these behaviours/rating and language scores. Interaction analysis and simple slopes explored effect modification by FC. OUTCOMES & RESULTS: There was no evidence that missed opportunities or praise were associated with language scores. Higher rates of successful directives in the unadjusted model and unsuccessful directives in the adjusted model were associated with lower 24-month-old receptive language scores (e.g., unsuccessful directives effect size (ES) = -0.41). The association between unsuccessful directives and receptive language was weaker when adjusting for co-occurring expansions (ES = -0.34). Both types of directives were associated with poorer receptive and expressive language scores in adjusted models at 36 and 48 months (e.g., unsuccessful directive and 48-month receptive language, ES = -0.66). FC was positively associated with 24-, 36- and 48-month language scores in adjusted models (e.g., receptive language at 24 months, ES = 0.21, at 48 months, ES = 0.18). Interaction analysis showed the negative association between successful directives and 24-month receptive language existed primarily in poorly connected dyads with low FC levels. CONCLUSIONS & IMPLICATIONS: These findings illustrate the effects of the combined interaction between different maternal communicative behaviours and features of the interaction itself on child language development, and the need to consider both in research and practice. Whilst more intrusive directives were associated with poorer language scores, this association attenuated when adjusting for co-occurring responsive expansions, and the association was strongest for children in lower quality interactions. This work may inform clinical practice by helping clinicians target the most appropriate communicative behaviours for specific mother-child dyads.

Associations between expressive and receptive language and internalizing and externalizing behaviours in a community-based prospective study of slow-to-talk toddlers.

BACKGROUND: Evidence suggests that language and social, emotional and behavioural (SEB) difficulties are associated in children and adolescents. When these associations emerge and whether they differ by language or SEB difficulty profile is unclear. This knowledge is crucial to guide prevention and intervention programmes for children with language and SEB difficulties. AIMS: To determine whether receptive and expressive language skills are associated with internalizing and externalizing behaviours in slow-to-talk toddlers. METHODS & PROCEDURES: In a community-based prospective study of 200 slow-to-talk children, language was measured at 24 and 36 months using Preschool Language Scale 4th Edition and at 48 months using Clinical Evaluation of Language Fundamentals-Preschool 2nd Edition. Internalizing and externalizing behaviours were measured by parent report at each age. Longitudinal data were analysed using repeated-measures regression, with up to three observations per child. Robust standard errors were used to account for non-independence of measures within participants. The shape of the associations were examined by fitting quadratic and cubic terms. The effects of confounders on the associations were examined. OUTCOMES & RESULTS: Receptive language had a negative linear association with internalizing behaviours after adjusting for confounders (ß = -0.16, 95% [CI = -0.26, -0.07], p = .001); and a negative curved association with externalizing behaviours after adjusting for biological confounders (ßquadratic = 0.08 [0.01, 0.15], p = .03, ßcubic = -0.04 [-0.07, -0.02], p = .001), attenuating after adjusting for environmental confounders (ßquadratic = 0.06 [-0.01, 0.13], p = .09, ßcubic = -0.03 [-0.06, -0.003], p = .03). The curvature suggests that the negative association with externalizing behaviours only existed for children with either very low or very high receptive language scores. After controlling for confounders, there was no evidence that expressive language scores were associated with internalizing (ß = -0.08, 95% [CI = -0.17, 0.01], p = .10) or externalizing behaviours (ß = 0.03, 95% [CI = -0.09, 0.18], p = .61). Tests of interaction revealed no evidence of a differential association by age. CONCLUSIONS & IMPLICATIONS: In 24-48-month-old slow-to-talk children, lower receptive language scores were associated with higher internalizing behaviours. The magnitude of the association was small. For children with very poor receptive language scores, lower receptive language skills were associated with higher externalizing behaviours. Young children with low receptive language abilities may be at risk of internalizing difficulties; those with very low receptive language skills may be at particular risk of externalizing difficulties. This has clinical implications for interventions for young children with receptive language difficulties.

Attitudes about the use of internet support groups and the impact among parents of children with Cornelia de Lange syndrome.

There is an abundance of information in the literature on patient experiences with Internet support groups (ISGs). However, studies exploring these experiences in a rare disease population are scarce, even though these families are often at a disadvantage for resources, reliable information, and support. The aim of the current study was to explore the experiences with ISGs for parents of children with Cornelia de Lange syndrome (CdLS), a rare genetic diagnosis, in order to better understand the impact on emotional support and their child's medical care. Focus groups were conducted to inform the design of a large-scale internet survey. The survey asked parents closed- and open-ended questions regarding experiences with ISGs, with a focus on the psychosocial, medical, and logistical aspects. The survey found that 141/170 (82.6%) respondents have visited an Internet-based support group to find support or information about their child's CdLS diagnosis. The majority of respondents (71.7%) reported that ISGs have been helpful in finding emotional support, with the most common areas impacted as a result of ISG participation being behavior toward their children and family dynamic. Regarding medical care, most respondents (63.9%) reported that ISGs have been helpful in finding medical information and support, with the most commonly impacted areas of their child's care including day-to-day management, diet, therapy interventions, and healthcare providers. These findings provide a greater understanding of the role of Internet networking in healthcare and may inform future approaches to medical care and psychosocial support for rare, complex genetic diagnoses. © 2016 Wiley Periodicals, Inc.

Benefits and limitations of a multidisciplinary approach to individualized management of Cornelia de Lange syndrome and related diagnoses.

Given the clinical complexities of Cornelia de Lange Syndrome (CdLS), the Center for CdLS and Related Diagnoses at The Children's Hospital of Philadelphia (CHOP) and The Multidisciplinary Clinic for Adolescents and Adults at Greater Baltimore Medical Center (GBMC) were established to develop a comprehensive approach to clinical management and research issues relevant to CdLS. Little work has been done to evaluate the general utility of a multispecialty approach to patient care. Previous research demonstrates several advantages and disadvantages of multispecialty care. This research aims to better understand the benefits and limitations of a multidisciplinary clinic setting for individuals with CdLS and related diagnoses. Parents of children with CdLS and related diagnoses who have visited a multidisciplinary clinic (N = 52) and who have not visited a multidisciplinary clinic (N = 69) were surveyed to investigate their attitudes. About 90.0% of multispecialty clinic attendees indicated a preference for multidisciplinary care. However, some respondents cited a need for additional clinic services including more opportunity to meet with other specialists (N = 20), such as behavioral health, and increased information about research studies (N = 15). Travel distance and expenses often prevented families' multidisciplinary clinic attendance (N = 41 and N = 35, respectively). Despite identified limitations, these findings contribute to the evidence demonstrating the utility of a multispecialty approach to patient care. This approach ultimately has the potential to not just improve healthcare for individuals with CdLS but for those with medically complex diagnoses in general. © 2016 Wiley Periodicals, Inc.

Intimate Partner Violence and Child and Adolescent Cognitive Development: A Systematic Review.

Intimate partner violence (IPV) is a public health and human rights issue, with millions of children affected worldwide. While several reviews have explored the emotional-behavioural functioning of children exposed to IPV, this review aimed to examine the relationship between children's exposure to IPV and their cognitive development, and to identify associated factors such as aspects of parenting. The databases MEDLINE, PsycInfo, EMBASE, Family and Society Studies Worldwide, CINAHL, and ERIC were searched using key words related to IPV, such as domestic, family, partner, interparental, spousal, marital, violence, abuse, aggression, assault, combined with key words related to cognitive functioning, such as neuropsychological, executive, intelligence, learning, memory, and key words related to children and adolescents. A total of 38 studies met the criteria for review which included reporting an estimate of the relationship between IPV and cognition using direct assessments of cognitive functioning. Approximately 70% of studies found a relationship between IPV and poorer cognitive functioning, with general IQ the most frequently assessed domain of functioning, followed by verbal abilities and academic skills. Most studies assessed skills during early childhood, with fewer studies assessing children during middle childhood and adolescence. Results were consistent across cognitive domains and developmental stages. In terms of factors associated with IPV and cognition, a range of demographic, individual, and family factors were included, with several studies exploring mediating and moderating mechanisms. The findings suggest that IPV in childhood is associated with poorer cognitive skills across a range of domains. Implications for policy, practice and research are discussed.

Children's language abilities at age 10 and exposure to intimate partner violence in early childhood: Results of an Australian prospective pregnancy cohort study.

BACKGROUND: Approximately one in four children in Australia have mothers who experience intimate partner violence (IPV). These children are at risk of poor mental health. Less is known about their language outcomes, despite evidence that childhood adversity threatens neurodevelopment, and the home environment effects language development. OBJECTIVE: This study aimed to examine the relationship between early childhood IPV exposure and language outcomes (receptive vocabulary, general language, pragmatic language) at age 10, including the influence of maternal depressive symptoms. PARTICIPANTS AND SETTING: Participants were 615 mothers and their first-born child participating in a prospective, community-based pregnancy cohort study in Melbourne. METHODS: Mothers reported their experience of IPV and depressive symptoms in the first and fourth year postpartum. At 10 years postpartum, children's receptive vocabulary was directly assessed and mothers reported on their child's general and pragmatic language skills. RESULTS: Exposure to IPV was related to scores indicating poorer abilities in receptive vocabulary (d=-0.26, p = .009), general language (d = 0.23, p = .047) and pragmatic language skills (d = 0.41, p < .001) at age 10. After adjusting for maternal depressive symptoms, evidence remained for the relationship with pragmatic language (d=-0.32, p = .006), and a trend for receptive vocabulary (d=-0.20, p = .052). CONCLUSIONS: At a community-level, children whose mothers experienced IPV during the child's first four years had poorer language skills in middle childhood than children whose mothers did not experience IPV. This is important because poor child language skills are associated with adverse outcomes across the lifespan including academic under-achievement and mental health problems. Clinical implications are discussed.

Intimate partner violence, maternal depression, and pathways to children's language ability at 10 years.

Intimate partner violence (IPV) between parents is associated with poorer child language development. This study aimed to examine pathways from IPV and maternal depressive symptoms in children's 1st year to language skills at 10 years. Pathways were examined via IPV, maternal depressive symptoms, and maternal involvement in home learning activities (e.g., reading, storytelling) at age 4. A secondary aim was to examine whether these pathways differed by child gender. Data were drawn from 1,507 mothers and their firstborn children participating in a community-based prospective longitudinal study. At child age 1 and 4 years, mothers reported IPV using the Composite Abuse Scale (CAS) and completed a depression scale. At child age 10 years, mothers completed the Children's Communication Checklist (2nd edition) Short Form and 4 pragmatic subscales, and children completed a receptive vocabulary test. Results provided some evidence that maternal depressive symptoms at 4 years postpartum may be an important mechanism by which exposure to IPV and maternal depressive symptoms in the child's 1st year is associated with poorer language at age 10. These pathways remained evident after accounting for social disadvantage, number of siblings, and concurrent IPV exposure at 10 years. There was little evidence that the pathways were mediated by maternal involvement or differed by gender. Implications for speech pathology, health, and education professionals concern identifying and supporting the language needs of children in family contexts where IPV is present. Intervention strategies for families affected by IPV such as supporting maternal mental health and the mother-child relationship could be extended to support child language development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Intimate partner violence and child outcomes at age 10: a pregnancy cohort.

OBJECTIVE: Assess the mental health, physical health, cognitive and language development of 10-year old children in families where mothers have reported intimate partner violence (IPV) compared with children with no reported IPV exposure. DESIGN: Prospective pregnancy cohort. Maternal report of IPV (Composite Abuse Scale) at 1, 4 and 10 years. Maternal and direct assessment of child mental health (probable psychiatric diagnosis, anxiety and emotional/behavioural difficulties), cognition (IQ and executive function), language (general, pragmatic and receptive) and physical health at 10 years. SETTING: A subsample of 615 mother-child dyads drawn from a pregnancy cohort of 1507 nulliparous women recruited from six public hospitals in Melbourne, Australia. RESULTS: Any IPV exposure from infancy to age 10 was associated with poorer child outcomes at age 10. Specifically, twice the odds of a probable psychiatric diagnosis, emotional/behavioural difficulties, impaired language skills (general and pragmatic), and having consulted a health professional about asthma or sleep problems. IPV exposure at age 10 associated with two to three times higher odds of all mental health outcomes, elevated blood pressure and sleep problems. Early life exposure alone (at 1 and/or 4 years) associated with three times higher odds of a general language problem and asthma at age 10. CONCLUSION: The high prevalence of IPV and increased risk of poorer health and development among children exposed highlights the burden of ill health carried by children in families experiencing IPV. Fewer difficulties where exposure was limited to the early years builds the case for better identification, understanding and resourcing of effective early intervention.

Genetic risk perception and reproductive decision making among people with epilepsy.

We investigated estimated offspring risk among people with epilepsy and factors important in the family-planning process. Data were collected for 88 participants using a questionnaire assessing perceived risk of offspring to develop epilepsy, importance of factors in the reproductive decision-making process, decision to have fewer children, and association between risk perception and family planning decisions. Thirty-four percent of participants had fewer children because of their epilepsy. Concerns about the ability to care for a child (p < 0.0001) and passing epilepsy onto a child (p = 0.003) were associated with the decision to have fewer children. The mean estimated risk of offspring to develop epilepsy was 26%, a 4-fold increase over estimated population risks. Genetic counseling may be beneficial for people with epilepsy, given the considerable overestimation of offspring risk.

Infant sleep and child mental health: a longitudinal investigation.

OBJECTIVE: To determine whether infants with severe persistent sleep problems are at increased risk of (1) meeting diagnostic criteria for a psychiatric disorder (age 10 years), and (2) having elevated symptoms of mental health difficulties (ages 4 and 10 years), in comparison with infants with settled sleep. DESIGN AND SETTING: Prospective longitudinal community cohort study-the Maternal Health Study. Mothers completed questionnaires/interviews at 15 weeks' gestation; 3, 6, 9 and 12 months post partum; and when their child turned 4 and 10 years old. Measures included parental report of infant night waking and sleep problems and child mental health (Strengths and Difficulties Questionnaire; Spence Children's Anxiety Scale; Development and Well-being Assessment). PARTICIPANTS: 1460 mother-infant dyads. RESULTS: 283 (19.4%) infants had persistent severe sleep problems, 817 (56.0%) had moderate/fluctuating sleep problems and 360 (24.7%) infants were settled. Infants with persistent severe sleep problems were more likely to report emotional symptoms at age 4 (adjusted odds ratio (AOR)=2.70, 95% CI 1.21 to 6.05, p=0.02), and meet diagnostic criteria for an emotional disorder at age 10 (AOR=2.37, 95% CI 1.05 to 5.36, p=0.04). Infants with persistent severe sleep problems also had elevated symptoms of separation anxiety (AOR=2.44, 95% CI 1.35 to 4.41, p<0.01), fear of physical injury (AOR=2.14, 95% CI 1.09 to 4.18, p=0.03) and overall elevated anxiety (AOR=2.20, 95% CI 1.13 to 4.29, p=0.02) at age 10. CONCLUSIONS: Infants with persistent severe sleep problems during the first postnatal year have an increased risk of anxiety problems and emotional disorders at age 10.

Physical and mental health of women exposed to intimate partner violence in the 10 years after having their first child: an Australian prospective cohort study of first-time mothers.

OBJECTIVE: To investigate mental and physical health of mothers exposed to recent and early postpartum intimate partner violence (IPV) in the 10 years after having their first child. DESIGN: Prospective pregnancy cohort study. SETTING: Women were recruited at six metropolitan public maternity hospitals in Melbourne, Australia and followed up at 1, 4 and 10 years post partum. STUDY MEASURES: Exposure to physical and/or emotional IPV was measured using the Composite Abuse Scale at 1, 4 and 10 years. At 10-year follow-up, mothers reported on physical and mental health, and functional health status. PARTICIPANTS: 1507 first-time mothers enrolled at mean of 15 weeks' gestation. RESULTS: One in three women experienced IPV during the 10 years after having their first child. Women experiencing recent IPV (19.1%) reported worse physical and mental health than women not reporting IPV. Compared with women not reporting IPV, women experiencing recent IPV had higher odds of poor functional health status (Adj OR=4.5, 95% CI 3.2 to 6.3), back pain (Adj OR=2.0, 95% CI 1.4 to 2.9), incontinence (Adj OR=1.8, 95% CI 1.2 to 2.6), depressive symptoms (Adj OR=4.9, 95% CI 3.2 to 7.5), anxiety (Adj OR=5.1, 95% CI 3.0 to 8.6) and post-traumatic stress symptoms (Adj OR=7.2, 95% CI 4.6 to 11.1) at 10 years. Women with past IPV at 1 and/or 4 years (15.7% of the cohort) also had higher odds of physical and mental health problems. There was evidence of a gradient in health outcomes by recency of exposure to IPV. CONCLUSIONS: Both recent and past exposure to IPV are associated with poor maternal physical and mental health 10 years after a first birth. Health services and advocacy organisations providing support to women need to be aware of the consistent relationship between IPV and a range of physical and mental health conditions, which may persist even after IPV appears to have ceased.