Biallelic OTUD6B variants associated with a Kabuki syndrome-like disorder in three siblings: A clinical report and literature review.

Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clinical findings similar to those of previously reported individuals. However, clinical manifestations such as long palpebral fissures, prominent and cupped ears, developmental delay, growth deficiency, persistent fetal fingertip pads, vertebral anomaly, and seizures in the proband were initially suggestive of KS. In addition, previously unreported clinical manifestations such as delayed eruption of primary dentition, soft doughy skin with reduced sweating, and mirror movements present in our patients suggest an expansion of the phenotype, and we perform a literature review to update on current information related to OTUD6B and human gene-disease association.

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

PURPOSE: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. METHODS: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. RESULTS: The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. CONCLUSION: We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed "SNAREopathies."

Meaning-making and psychological adjustment to cancer: development of an intervention and pilot results.

PURPOSE/OBJECTIVES: To develop an intervention that uniquely addresses the existential impact of cancer through meaning-making coping strategies and to explore the intervention's impact on psychological adjustment. DESIGN: Descriptive, qualitative approach to develop the intervention; one-group pre- and post-test design to pilot test the intervention. SETTING: Patients' homes or ambulatory oncology clinics affiliated with a university health center in eastern Canada. SAMPLE: 18 participants who were newly diagnosed in the past three months (n = 14), had completed treatment (n = 1), or were facing recurrence (n = 3) of breast (n = 10) or colorectal (n = 8) cancer. METHODS: Data were collected during interviews using a prototype intervention for trauma patients, and content was analyzed on an ongoing basis to fit the needs of the cancer population. Pretest and post-test questionnaires were administered to determine the intervention's effect. MAIN RESEARCH VARIABLES: Meaning-making intervention (MMI), patients' background variables, disease- or treatment-related symptoms, and psychological adjustment. FINDINGS: The MMI for patients with cancer consisted of as many as four two-hour, individualized sessions and involved the acknowledgment of losses and life threat, the examination of critical past challenges, and plans to stay committed to life goals. At post-test, participants significantly improved in self-esteem and reported a greater sense of security in facing the uncertainty of cancer. CONCLUSIONS: Findings suggest that meaning-making coping can be facilitated and lead to positive psychological outcomes following a cancer diagnosis. IMPLICATIONS FOR NURSING: The MMI offers a potentially effective and structured approach to address and monitor cancer-related existential issues. Findings are useful for designing future randomized, controlled trials.