SOX5: Lamb-Shaffer syndrome-A case series further expanding the phenotypic spectrum.

To delineate further the clinical phenotype of Lamb-Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype-phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant.

Communication with children and adolescents about the diagnosis of a life-threatening condition in their parent.

Many adults diagnosed with a life-threatening condition have children living at home; they and their partners face the dual challenge of coping with the diagnosis while trying to maintain a parenting role. Parents are often uncertain about how, when, and what to tell their children about the condition, and are fearful of the effect on their family. There is evidence that children are often aware that something is seriously wrong and want honest information. Health-care professionals have a key role in supporting and guiding parents and caregivers to communicate with their children about the diagnosis. However, the practical and emotional challenges of communicating with families are compounded by a scarcity of evidence-based guidelines. This Review considers children's awareness and understanding of their parents' condition, the effect of communication around parental life-threatening condition on their wellbeing, factors that influence communication, and the challenges to achieving effective communication. Children's and parents' preferences about communication are outlined. An expert workshop was convened to generate principles for health-care professionals, intended as practical guidance in the current absence of empirically derived guidelines.

Communication with children and adolescents about the diagnosis of their own life-threatening condition.

When a child is diagnosed with a life-threatening condition, one of the most challenging tasks facing health-care professionals is how to communicate this to the child, and to their parents or caregivers. Evidence-based guidelines are urgently needed for all health-care settings, from tertiary referral centres in high-income countries to resource limited environments in low-income and middle-income countries, where rates of child mortality are high. We place this Review in the context of children's developing understanding of illness and death. We review the effect of communication on children's emotional, behavioural, and social functioning, as well as treatment adherence, disease progression, and wider family relationships. We consider the factors that influence the process of communication and the preferences of children, families, and health-care professionals about how to convey the diagnosis. Critically, the barriers and challenges to effective communication are explored. Finally, we outline principles for communicating with children, parents, and caregivers, generated from a workshop of international experts.

Association of Maternal and Paternal Depression in the Postnatal Period With Offspring Depression at Age 18 Years.

Importance: Paternal depression during the postnatal period has been associated with adverse child outcomes. Family environment has been reported as a pathway for risk transmission from fathers to children. The influence of paternal depression during the postnatal period on offspring depression remains to be clarified. Objective: To investigate the association between paternal depression in the postnatal period and offspring depression and explore potential mediating and moderating factors that influence any association between paternal and offspring depression. Design, Setting, and Participants: This prospective study of a UK community-based birth cohort (the Avon Longitudinal Study of Parents and Children) of parents and their adolescent offspring investigated associations between paternal depression during the postnatal period and offspring depression at age 18 years. We tested a hypothesized moderator (ie, sex) and conducted path analysis to examine hypothesized mediators (ie, depression in the other parent, couple conflict, and paternal involvement and emotional problems, conduct problems, and hyperactivity in offspring at age 3.5 years) of the associations between both paternal and maternal depression and offspring depression. Data collection for the Avon Longitudinal Study of Parents and Children began in 1991 and is ongoing. Data analysis for this study was conducted from June 2015 to September 2018. Exposures: Depression symptoms in fathers at 8 weeks after the birth of their children. Main Outcomes and Measures: Offspring depression symptoms at age 18 years, using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Results: A total of 3176 father-offspring pairs were analyzed; of the children, 1764 were girls (55.5%) and 1412 (44.5%) were boys. Paternal mean (SD) age at delivery was 29.6 (9.6) years. The offspring of fathers who had depression during the postnatal period were at increased risk of experiencing depression symptoms at age 18 years (ß = 0.053 [95% CI, 0.02-0.09]). The association is mediated by maternal depression at 8 months after birth (ß = 0.011 [95% CI, 0.0008-0.02]; 21% [0.011/0.053]) and conduct problems at 42 months after birth (ß = 0.004; [95% CI , -0.00004 to 0.009]; 7.5% [0.004/0.053]). Couple conflict and paternal involvement do not mediate this association. The increased risk is seen in girls but not boys (interaction ß = 0.095; P = .01). Conclusions and Relevance: The association between paternal depression in the postnatal period and depression in girls at age 18 years is partially explained by maternal depression. Couple conflict and paternal involvement were not found to play a role in the risk of transmission; this contrasts with the role that couple conflict was found to play in the risk of childhood behavior problems. Conduct problems in childhood appear to be a pathway for risk transmission between paternal depression and subsequent depression in offspring at age 18 years.

Paternal depression in the postnatal period and child development: mediators and moderators.

OBJECTIVE: To explore potential mediating and moderating factors that influence the association between paternal depression in the postnatal period and subsequent child behavioral and emotional problems. METHODS: A population-based cohort (N = 13,822) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was recruited during pregnancy. Paternal and maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale at 8 weeks after the birth of the child. Child outcomes were assessed at 3.5 years by using the Rutter revised preschool scales and at 7 years by using the Strengths and Difficulties Questionnaire. Path analysis was used to assess hypothesized mediators (ie, depression in the other parent, couple conflict, and paternal noninvolvement) of the associations between both paternal and maternal depression and child outcomes. We also tested for hypothesized moderators (ie, paternal education and antisocial traits). RESULTS: Family factors (maternal depression and couple conflict) mediated two-thirds of the overall association between paternal depression and child outcomes at 3.5 years. Similar findings were seen when children were 7 years old. In contrast, family factors mediated less than one-quarter of the association between maternal depression and child outcomes. There was no evidence of moderating effects of either parental education or antisocial traits. CONCLUSIONS: The majority of the association between depression in fathers postnatally and subsequent child behavior is explained by the mediating role of family environment, whereas the association between depression in mothers and child outcomes appears to be better explained by other factors, perhaps including direct mother-infant interaction.

Parental depression and child temperament: assessing child to parent effects in a longitudinal population study.

Current research supports a link between maternal depression and difficult child temperament. The direction of effect is often assumed to be from parent to child, but few studies have addressed child to parent effects. In a large cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=14663), we aimed to further existing knowledge by investigating the relationship between maternal and paternal depressive symptoms and child temperament, and determining the direction of any effects found. Data was collected at 2 time-points (when the children were 6 and 24 months old), using the Edinburgh Postnatal Depression Scale and the Mood and Intensity subscales of the Carey Temperament Scales. Significant parent to child effects were seen, with maternal and paternal depressive symptoms at Time 1 leading to more difficult temperament at Time 2. Father to child effects were significant only in male children. Little evidence was found for child to parent effects.