Severe congenital ichthyosiform dermatosis in CHIME syndrome successfully treated with ixekizumab.

Coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, conductive hearing loss, and epilepsy (CHIME) syndrome is a rare autosomal recessive neuroectodermal disorder caused by PIGL gene mutations. There is emerging literature to support the use of interleukin-17 (IL-17) antagonists in the treatment of certain ichthyosiform dermatoses. Here, we report a case of severe ichthyosiform dermatosis in a child with CHIME syndrome who was recalcitrant to multiple topical medications and dupilumab. This is the first reported case of successful treatment of congenital ichthyosiform dermatosis in a CHIME syndrome patient with ixekizumab, an IL-17A antagonist.

Child with a mild CHIME syndrome phenotype and carrying a novel p.(Asp52Asn) PIGL pathogenic variant in association with the previously reported p.(Leu167Pro) variant: A case report.

Coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies (CHIME) syndrome is a very rare autosomal recessive neuroectodermal disorder related to PIGL gene mutations. Here, we report a patient who showed an initial delay in psychomotor development and skin abnormalities consistent with CHIME syndrome but with atypical clinical features and laboratory findings. In line with our clinical suspicion, the c.500T>C, p.(Leu167Pro) variant (found in all the previously described cases of CHIME syndrome) was found on the paternal allele. A novel "likely pathogenic" PIGL missense variant (c.154G>A, p.(Asp52Asn)) was detected on the maternal allele. This case provides new insights into the clinical spectrum of CHIME syndrome and highlights the potential for phenotypic/genotypic variations.

Journey to wellness: A socioecological analysis of veterans in recovery from substance use disorders.

Substance use disorders are increasingly prevalent among veterans in the United States. Veterans in recovery face unique challenges, such as high rates of psychiatric comorbidities, difficulties adjusting to civilian life, and inadequate housing and mental health services. While prior research has explored veterans' experiences in recovery, studies have not implemented a multilevel perspective in their analyses. The current qualitative study examined how individual veteran experiences intersect with interpersonal and systemic factors. Semistructured focus groups were conducted with veterans who were former or current residents of recovery homes (N = 20). Thematic analysis was utilized to explore veterans' personal experiences through the CHIME-D framework (connectedness, hope & optimism, identity, meaning in life, empowerment, and difficulties). The data were further analyzed within a socioecological model (intrapersonal, interpersonal, and community). Each component of the CHIME-D framework was salient across all focus groups, with connectedness, empowerment, and difficulties being the most prominent themes that occurred across all socioecological levels. Results suggest that recovery initiatives can effectively assist veterans by promoting empowerment, facilitating social connections, and addressing cooccurring difficulties across multiple socioecological contexts. Additionally, treatment programs should encourage veterans to take on meaningful roles in their communities. Future research should continue to explore veterans' recovery experiences using a socioecological model.

Mapping landscape canopy nitrogen content from space using PRISMA data.

Satellite imaging spectroscopy for terrestrial applications is reaching maturity with recently launched and upcoming science-driven missions, e.g. PRecursore IperSpettrale della Missione Applicativa (PRISMA) and Environmental Mapping and Analysis Program (EnMAP), respectively. Moreover, the high-priority mission candidate Copernicus Hyperspectral Imaging Mission for the Environment (CHIME) is expected to globally provide routine hyperspectral observations to support new and enhanced services for, among others, sustainable agricultural and biodiversity management. Thanks to the provision of contiguous visible-to-shortwave infrared spectral data, hyperspectral missions open enhanced opportunities for the development of new-generation retrieval models of multiple vegetation traits. Among these, canopy nitrogen content (CNC) is one of the most promising variables given its importance for agricultural monitoring applications. This work presents the first hybrid CNC retrieval model for the operational delivery from spaceborne imaging spectroscopy data. To achieve this, physically-based models were combined with machine learning regression algorithms and active learning (AL). The key concepts involve: (1) coupling the radiative transfer models PROSPECT-PRO and SAIL for the generation of a wide range of vegetation states as training data, (2) using dimensionality reduction to deal with collinearity, (3) applying an AL technique in combination with Gaussian process regression (GPR) for fine-tuning the training dataset on in field collected data, and (4) adding non-vegetated spectra to enable the model to deal with spectral heterogeneity in the image. The final CNC model was successfully validated against field data achieving a low root mean square error (RMSE) of 3.4 g/m2 and coefficient of determination (R 2) of 0.7. The model was applied to a PRISMA image acquired over agricultural areas in the North of Munich, Germany. Mapping aboveground CNC yielded reliable estimates over the whole landscape and meaningful associated uncertainties. These promising results demonstrate the feasibility of routinely quantifying CNC from space, such as in an operational context as part of the future CHIME mission.

Using the CHIME Personal Recovery Framework to Evaluate the Validity of the MHRM-10 in Individuals with Psychosis.

The recovery movement has revealed that outcomes which focuses on just symptoms and functioning may not be holistic and that consumer-rated outcomes may contribute to a more holistic and person-centric care model. However, a brief and effective measure is required in clinical settings; hence, the aim of the current study is to evaluate the psychometric properties of the briefest personal recovery measure- Mental Health Recovery Measure-10 items, using the CHIME (Connectedness, Hope and optimism about the future, Identity, Meaning in life, Empowerment) personal recovery framework. 64 outpatients with schizophrenia or schizoaffective disorder were assessed at two time points, 2 weeks apart. Data collected included sociodemographic information, MHRM-10, Psychological factors related to the CHIME framework, in respective order: RYFF subscale positive relations with others; Herth Hope Index (HHI); Internalized Stigma of Mental Illness (ISMI) and RYFF subscale self-acceptance; World Health Organization Quality of Life- BRIEF (WHOQOL-BREF); Empowerment, and Clinical factors- symptoms as measured by Positive and Negative Syndrome Scale, functioning (PSP) and depressive symptoms (CDSS). MHRM-10 demonstrated convergent validity with CHIME personal recovery psychological factors (all ρ > 0.5). MHRM-10 had excellent internal consistency (Cronbach's alpha = 0.904) and adequate test-retest reliability (ρ = 0.742, p < 0.001). Initial factor structure analysis revealed a one factor structure. The MHRM-10 is a valid instrument for use and can serve as a tool to facilitate a more collaborative and person-centric model of care for individuals with psychosis.

An Asian study on clinical and psychological factors associated with personal recovery in people with psychosis.

BACKGROUND: Despite the rising recognition of personal recovery, there is a lack of research on personal recovery in individuals with psychosis in Singapore. This study aims to evaluate the psychometric properties of the QPR-15 using the CHIME personal recovery framework and to examine its associations with clinical recovery factors. METHODS: Sixty-six stable outpatients were recruited and assessed at two time points approximately 2 weeks apart. Convergent validity was examined through Spearman correlations with scores on CHIME-related psychological factors: connectedness (Ryff subscale- positive relations with others), hope (Herth Hope Index- abbreviated), identity (Ryff subscale- self-acceptance, Internalized Stigma of Mental Illness- Brief), meaning (World Health Organization Quality of Life Assessment-Brief Form), empowerment (Empowerment Scale). Pearson's correlation was used to examine the test-retest reliability, while Cronbach's alpha was used to examine internal consistency. The initial factor structure was evaluated via principal component analysis, Velicer's minimum average partial (MAP) criteria, parallel analysis, and a scree plot. Spearman correlations and hierarchical multiple linear regression (controlling for age and gender) were employed to examine the association of clinical (symptoms and functioning) and psychological factors with the QPR-15. RESULTS: The QPR-15 demonstrated convergent validity with all CHIME-related psychological factors (rs ranged from 0.472 to 0.687). Internal consistency was excellent (Cronbach's alpha = 0.934), and test-retest reliability was adequate (r = 0.708). Initial factor structure evaluations revealed a one-factor model. Correlations of clinical factors with the QPR-15 were mostly low (rs ranged from - 0.105 to - 0.544) but significant, except for depressive symptoms (CDSS: rs = - 0.529 to - 0.544), while correlations were moderate for psychological factors. Clinical factors significantly explained 28.3-31.8% of the variance of the QPR-15. Adding psychological factors significantly increased the model variance at baseline (∆ adjusted R2 = 0.369, F change < 0.001) and at time point 2 (∆ adjusted R2 = 0.208, F change < 0.001). CONCLUSION: Our results provide preliminary evidence that the QPR-15 has adequate psychometric properties in Singapore and encompasses the CHIME personal recovery framework. In addition, our results suggest that clinical recovery and personal recovery are not substitutes for each other but rather are complementary, thereby promoting a more holistic evaluation of recovery in people with psychosis. Implications are discussed.

The art of recovery: outcomes from participatory arts activities for people using mental health services.

BACKGROUND: There is a growing evidence base for the use of participatory arts for the purposes of health promotion. In recent years, recovery approaches in mental healthcare have become commonplace in English speaking countries amongst others. There are few studies that bring together these two fields of practice. AIMS: The two aims of this study were (a) to investigate the validity of the CHIME framework for characterising the experience of Participatory Arts and (b) to use the CHIME framework to investigate the relationship between participatory arts and mental health recovery. METHOD: The study employed a two-phase methodology: a rapid review of relevant literature followed by secondary analysis of qualitative data collected from 38 people who use mental health service who took part in participatory arts activities designed to improve mental health. RESULTS: Each of the recovery processes identified by CHIME are present in the qualitative research literature as well as in the data of the secondary analysis. CONCLUSIONS: Participatory arts activities produce outcomes which support recovery, specifically including enhancing connectedness and improving hope. They can be recommended to people living with mental health problems.

Personal recovery for special populations: a qualitative study exploring the role of special interest meetings within 12-step fellowships.

BACKGROUND: This study explores how Special Interest Meetings (SIMs), also called topic-specific meetings (e.g., meetings for young people), support recovery in 12-Step fellowships for Special Populations like young people, women and LGBTQIA+ members. Despite their emergence to address the needs of these groups, the specific ways Special Interest Meetings contribute to recovery experiences are understudied. METHODS: In-depth interviews were conducted with 12 participants who had attended Special Interest Meetings in 12-Step fellowships to explore the role of these meetings in recovery. The interviews were analysed using the CHIME-D personal recovery framework (Connectedness, Hope, Identity, Meaning in life, Empowerment, Difficulties). RESULTS: Special Interest Meetings serve as recovery pathways for Special Populations, incorporating CHIME-D elements to aid recovery and address challenges. This study found four "Special Population Pathways" for recovery: Traditional, Hybrid, SIM-Only, and Outside-Sim Hybrid Pathway. CONCLUSIONS: Special Interest Meetings address specific challenges like discrimination and exclusion faced by Special Populations in recovery. These meetings offer tailored support, deeper connections, improved recovery outcomes, and a sense of empowerment. The existence of "Special Population Pathways" emphasises the ongoing need to address diverse individuals' specific needs throughout the recovery process.

We-Care-Well: exploring the personal recovery of mental health caregivers through Participatory Action Research.

Family caregivers play a critical role in supporting the recovery journeys of their loved ones, yet the recovery journeys of family caregivers have not been well-explored. Using a Participatory Action Research approach, we explore the personal recovery journeys of family caregivers for individuals with mental illness. This case study involved piloting and exploring the impact of a novel online workshop series offered to mental health caregivers at Ontario Shores Center for Mental Health Sciences. Recovery courses and workshops conventionally engage patients living with mental health conditions. In the current case, the recovery model is adapted to the needs and experiences of their family caregivers, resulting in a pilot workshop series called "We Care Well". Through participant-led discussions, interactive and take-home activities, and experiential learning, caregivers co-created workshop content and engaged in peer-learning on seven personal recovery-oriented topics. This included: self-care, resilience-building, non-violent communication, storytelling, and mental health advocacy. Throughout the sessions, participants implemented their learnings into their caregiving roles, and shared their experiences with the group to progress through their own recovery journeys. The We Care Well series was found to be an effective intervention to adapt and apply the personal recovery framework to mental health caregivers. PAR, and co-design are viable approaches to engage caregivers in mental health research, and can facilitate knowledge exchange, as well as relationship building with peers and program facilitators.

Scalability, test-retest reliability and validity of the Brief INSPIRE-O measure of personal recovery in psychiatric services.

Introduction: Mental health services have transitioned from treating symptoms to emphasizing personal recovery. Despite its importance, integrating personal recovery into clinical practice remains work in progress. This study evaluates the psychometric qualities of the Brief INSPIRE-O, a five-item patient-reported outcome measure assessing personal recovery. Method: The study collected data from 2018 to 2020 at the Mental Health Services, Capital Region of Denmark, using an internet-based system examining 8,192 non-psychotic patients - receiving outpatient treatment. Materials: This study evaluated the Brief INSPIRE-O and used measures of symptomatology (SCL-10), well-being (WHO-5), and social functioning (modified SDS). Results: The study population comprised 76.8% females with a mean age of 32.9 years, and diagnoses included anxiety (28%), depression (34%), and personality disorder (19%). The mean Brief INSPIRE-O score (39.9) was lower than the general population norm (71.1). The Brief INSPIRE-O showed acceptable test-retest reliability (0.75), scalability (0.39), and internal consistency (0.73). Correlations with other mental health criteria were in the expected direction for symptomatology (-0.46), well-being (0.60), and social functioning (-0.43) and remained consistent across diagnoses. Discussion: The Brief INSPIRE-O demonstrated strong psychometric qualities and could be recommended as a measure of personal recovery for use in both research and clinical practice. Its strong theoretical basis and short completion time make it suitable for use for research. Incorporating Brief INSPIRE-O into clinical assessment will further support the process of mental health systems re-orientating towards personal recovery.

Systematic review and citation content analysis of the CHIME framework for mental health recovery processes: recommendations for developing influential conceptual frameworks.

Objectives: To identify design features of the CHIME conceptual framework of mental health recovery which are associated with high rates of citation. Research Design and Methods: Systematic review of all citations of the Connectedness, Hope, Identity, Meaning, and Empowerment (CHIME) framework of mental health recovery. Papers citing CHIME were screened and extracted from three citation databases. Citation content analysis was used to investigate associations between nine CHIME design features. Citations were investigated across six forms of visibility: all citations; Anglophone vs non-Anglophone; academic vs non-academic; academic discipline; professional group; and clinical population. Results: There were 915 eligible documents identified. Six CHIME framework design features met predefined thresholds for high levels of influence: (i) using a systematic review methodology for development, (ii) adopting a memorable acronym, (iii) having disaggregable components, and being unaligned to a (iv) particular discipline (i.e., transdisciplinary), (v) professional group, or (vi) diagnostic population. Documents from Anglophone countries were more likely to cite CHIME with reference to trans-professional (χ2=3.96, df=1, p=0.05) and ethnicity sub-group analysis (p=0.039) design features than non-Anglophone documents. Non-academic documents were more likely to cite the acronym design feature than academic papers (χ2=5.73, df=1, p=0.01). Public Health-related publications were more likely to cite CHIME within a trans-diagnostic framework (χ2=16.39, df=1, p<0.001) than other disciplines. Conclusions: The influence and impact of conceptual frameworks for recovery are increased when the framework is underpinned by a systematic review, includes disaggregable components which can be summarized using a memorable acronym, and when the framework is transdisciplinary, trans-professional, and trans-diagnostic.

Exploring the Lived Experience on Recovery from Major Depressive Disorder (MDD) among Women Survivors and Five CHIME Concepts: A Qualitative Study.

OBJECTIVE: Depression is estimated to be the leading cause of disease by 2030 and is already the leading cause in women worldwide. In Malaysia, nearly 2.3 million people have experienced depression at least once. Yet, this problem has not been thoroughly investigated and addressed. Thus, a study exploring the lived experience of the survivors needs to be carried out. With most Major Depressive Disorder (MDD) patients being women compared to men, this study focused on women MDD survivors to understand their journey to recovery. Survivors or also called 'People with Lived Experience' (PWLE) have a range of first-hand experiences with treatment and recovery, making them an expert by experience. METHOD: A qualitative study was conducted using purposive sampling of four women survivors. This method was able to explore the experience of informants rigorously as it gave flexibility and encouraged discussion between researchers and informants. The data from in-depth interviews conducted were then analyzed using thematic analysis, focusing on the key concepts of CHIME conceptual framework of recovery. RESULTS: This study found four major themes with fifteen subordinate themes: survivor's efforts, challenges, social support, and hopes. The findings of this study were then integrated with CHIME framework, also known as the guiding philosophy of recovery for mental illness patients. CONCLUSION: These findings contributed to a better understanding of the recovery process and supports needed for MDD patients to recover. In addition, this study also gives hopes that MDD patients can recover, therefore breaking the social stigma still prevalent in the community. Based on these first-hand experiences shared by the survivors, it is hoped that the present interventions conducted by related organizations and caregivers can yield improvements so that the current patients who are still struggling with MDD can recover faster holistically. Limitations and implications for future research have also been discussed.

Understanding Protective Factors for Men at Risk of Suicide Using the CHIME Framework: The Primacy of Relational Connectedness.

Suicide is a global problem, ranking among the leading causes of death in many countries across the world. Most people who die by suicide are "under the radar", having never seen a mental health professional or been diagnosed with a mental illness. This article describes the protective factors for men experiencing suicidal thoughts, plans, and/or attempts who are "under the radar". Using in-depth qualitative interviews, we aimed to understand stakeholder perspectives on the protective factors that influence men's wellbeing. The pervasiveness of relational connectedness in men's narratives was identified as a central protective factor. Other key protective factors included meaningful activity, empowerment, and hope. These results have the potential to facilitate the development of focused community initiatives. More generally, the current research offers an example of a qualitative inquiry into men's wellbeing that focuses on strengths and positive factors in their lives and may provide a guide for future community-based suicide prevention research.

"Beyond laughter": a systematic review to understand how interventions utilise comedy for individuals experiencing mental health problems.

Introduction: There is evidence for the impact of comedy and humour for mental health and wellbeing. Existing systematic reviews have concluded laughter has a positive impact on wellbeing, however other potential benefits of comedy interventions have remained under explored. The aim of the current study was to synthesise current evidence for comedy/humour interventions and evaluate mechanisms through which comedy interventions may impact upon the recovery of those experiencing psychological distress, using the Connectedness, Hope, Identity, Meaning and Purpose and Empowerment (CHIME) framework. Methods: Five electronic databases were searched for studies exploring the impact of interventions using comedy on wellbeing and mental health recovery, from earliest record until January 2023. Grey literature was obtained via contacting experts in comedy interventions for mental health and supplemented by an internet search for comedy interventions. To be eligible for inclusion, studies had to include primary data, published in English or German, and explore a population of adults, with self-reported distress or a self-reported/diagnosed mental health condition. Studies included only explored interventions which utilised comedy as the main intervention and aimed to induce 'simulated' laughter, in response to a stimulus. 17 studies were included in the review. Results: Studies were found to have positive impact on mental health symptoms and several mechanisms of the CHIME framework for recovery, including connectedness, hope, identity and empowerment. Potential theorised mechanisms for change included confidence in new skills, promotion of social skills, opportunities for social interaction, laughter, vulnerability, and cognitive flexibility. The current review found that comedy/humour interventions are beneficial for mental health recovery and wellbeing and found preliminary evidence for a range of mechanisms through which comedy may have positive impact. Discussion: Further research should focus on qualitative exploration of the mechanisms by which comedy interventions may have impact on wellbeing and mental health recovery for specific populations and within different settings. It is concluded that there is a need for transdisciplinary collaboration in research on comedy interventions, which brings together the expertise of comedians delivering/developing interventions, those with lived experience of mental health issues and researchers from both health sciences and humanities disciplines.

Corrigendum: "Beyond laughter": a systematic review to understand how interventions utilise comedy for individuals experiencing mental health problems.

[This corrects the article DOI: 10.3389/fpsyg.2023.1161703.].

Neisseria lactamica Controlled Human Infection Model.

Neisseria lactamica is a nonpathogenic commensal of the human upper respiratory tract that has been associated with protection against N. meningitidis colonization and disease. We have previously utilized the N. lactamica controlled human infection model to investigate the protective effect of N. lactamica colonization on N. meningitidis colonization, the nature of cross-reactive immune responses mounted toward N. meningitidis following N. lactamica colonization, and the microevolution of N. lactamica over a 5-month colonization period. More recently, we have assessed the possibility of utilizing genetically modified strains of N. lactamica to enable use of the commensal as a vehicle for prolonged exposure of the nasopharynx of humans to antigens of interest, expressed in carried organisms. A controlled infection with N. lactamica expressing the meningococcal antigen NadA has been executed and the results demonstrate that this strategy is effective at generating immune responses to the target antigen. Throughout this chapter, we outline in a step-by-step manner the methodologies utilized when performing controlled human infection with N. lactamica including procedures relating to: (1) the dilution of N. lactamica stock vials to derive intranasal inocula, (2) the delivery of intranasal inocula to human volunteers, (3) the determination of N. lactamica colonization status following intranasal inoculation using oropharyngeal swabbing and nasal wash sampling, (4) the microbiological procedures utilized to identify N. lactamica colonization among study volunteers, and (5) the identification of N. lactamica colonies as strain Y92-1009 using polymerase chain reaction.

Modeling the effectiveness of social distancing interventions on the epidemic curve of coronavirus disease in Ethiopia.

SARS-CoV-2 infections are now spreading across the world. Different measures were used by governments around the world to combat the spread of COVID-19. The efficacy of social distancing approaches in reducing the spread of COVID-19 in Ethiopia was investigated using geospatial technologies and the CHIME model. The COVID-19 response was predicted, measured, and compared after 25%, 75%, and 95% social distancing interventions in Ethiopia. Social distancing strategies flatten and delay the epidemic curve, according to the model findings. The model result shows that most new events and hospitalizations were avoided when social distancing measures were in effect. Social distancing can provide a critical time for increasing healthcare capability, and the research findings could assist policymakers in estimating the immediate number of resources required and planning for potential COVID-19 initiatives in Ethiopia.

Effectiveness of personal recovery facilitators in adults with schizophrenia and other psychoses: A systematic review of reviews and narrative synthesis.

This review aimed to examine the evidence base for the use of personal recovery facilitators [non-psychopharmacological approaches] for adults with a diagnosis of schizophrenia and other psychoses. A systematic review (umbrella review) was conducted of reviews published in English between January 2010 and February 2022, which examined the effectiveness of personal recovery facilitators to support aspects of personal recovery as defined by the CHIME framework (connectedness, hope and optimism, identity, meaning and purpose, and empowerment). Twenty-one systematic reviews on thirteen different types of personal recovery facilitators [PRFs] were included in this umbrella review. Only one review sought to directly measure personal recovery processes according to the CHIME framework. Outcome measures mostly aligned with the processes of hope (21 reviews) and connectedness (19 reviews). Those related to empowerment (2 reviews), identity (5 reviews) and meaning and purpose (1 review) were less frequently the focus of PRFs. Yoga and music therapy showed the most promise as PRFs. Vocational treatments and integrated supported employment show good potential as personal recovery facilitators. However, together with narrative photovoice, art making and exhibition, they require further robust research to fully examine their impact. Personal recovery is only beginning to be considered as an intended outcome of interventions for persons with schizophrenia and other psychoses. This may be due in part to the continued predominance of the biomedical model approach to recovery within statutory services. Future evaluations of PRFs should include outcome measures that directly assess personal recovery according to the CHIME framework or other measures developed in consultation with recipients of these approaches. Review registration number and date: PROSPERO 2020 CRD42020215471: 10/11/20.

Validation of the Comprehensive Inventory of Mindfulness Experiences (CHIME) in Portuguese Children.

Objectives: Despite the increasing interest in mindfulness, there are few multifaceted mindfulness measures for children, mainly in Portuguese. Thus, this study developed the Portuguese version of the Comprehensive Inventory of Mindfulness Experiences (CHIME). Because this scale was initially created for adolescents, we also aimed to adapt it to children. Methods: After translating the original CHIME to Portuguese and adapting the wording for children, the instrument was administered to 223 9-10-year-olds, along with self-report measures of affect and quality of life, teacher-rated measures of inhibition, inattention, and emotional lability, and a performance-based attentional measure. We examined CHIME's factorial validity, inspected facets' reliability, and tested convergent, discriminant, and predictive validity. Results: Confirmatory factor analyses (CFA) supported a 7-factor structure of the scale, after removing the accepting and non-judgmental attitude facet. Factor loadings (> .34) and reliability indices (> .54) were acceptable, though the average variance extracted was less than desirable. Correlations with external correlates provided support to CHIME's convergent and divergent validity (rs range .13-.55, ps < .05). Finally, evidence of predictive validity was found with a regression analysis showing that external awareness (b = - .16) and openness to experience (b = - .17) predicted academic achievement. Conclusions: This study provided preliminary validity and reliability evidence on the Portuguese CHIME. This instrument can provide relevant insights about the mindfulness facets and offer useful indications for the development of evidence-based interventions in childhood.

Congenital diaphragmatic hernia and early lethality in PIGL-related disorder.

We report on three male siblings who presented prenatally with a nearly identical combination of congenital anomalies and who died shortly after preterm birth. The first baby was a singleton pregnancy, and the other two babies were dichorionic diamniotic twins. Key features included: left-sided congenital diaphragmatic hernia, inferior vermian dysgenesis/hypoplasia, prenasal edema, cleft palate, micropenis/ambiguous genitalia (in 2 of 3 babies), bilateral renal pelvic dilatation (in twins, first baby showed slightly enlarged kidneys) and polyhydramnios (in 2 of 3). Whole genome sequencing performed on DNA from all three babies revealed homozygous missense PIGL gene variants: c.438C>A, p.(Phe146Leu). Both parents were heterozygous carriers of the variant. The reporting clinical laboratory classified the change as a variant of uncertain significance (VUS), and concluded "A genetic diagnosis of autosomal recessive CHIME syndrome is possible". The PIGL gene has been reported to cause two different autosomal recessive conditions: CHIME syndrome and Mabry syndrome. CHIME (Zunich neuroectodermal syndrome) is characterized by ocular Colobomas, Heart defects, Ichthyosiform dermatosis, Mental retardation (intellectual disability), and Ear anomalies, including conductive hearing loss. Mabry [aka hyperphosphatasia mental retardation syndrome (HPMRS)] is characterized by severe developmental delay, moderate to severe intellectual disability, distinctive facial features, brachytelephalangy, increased serum levels of alkaline phosphatase (ALP), and recurrent seizures. Neonatal demise and lack of postmortem examination precluded assessment of some key features (including seizures, developmental delay, ALP levels, colobomas and deafness), but overlapping features observed included cleft palate, brain anomalies, genitourinary abnormalities and prenasal edema. Notably, diaphragmatic hernia is not a common feature of either condition, but is a cardinal feature of Fryns syndrome. The genetic etiology of Fryns syndrome has not been definitively established, although, much like CHIME and Mabry syndrome, can be caused by variants in glycosylphosphatidylinositol (GPI) anchor pathway genes. Our findings suggest further overlap between inherited GPI deficiencies, and possible expansion of the clinical phenotype of PIGL-related disorders to include prenatal presentations with congenital diaphragmatic hernia. Although reported as a VUS, we present phenotypic and familial segregation evidence that supports likely pathogenicity of the c.438C>A variant.