Refining of the electroclinical phenotype in familial and sporadic cases of CSNK2B-related Neurodevelopmental Syndrome.

CSNK2B encodes a regulatory subunit of casein kinase II, which is highly expressed in the brain. Heterozygous pathogenic variants in CSNK2B are associated with Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) (OMIM #618732), characterized by facial dysmorphisms, seizures, intellectual disability, and behavioral disturbances. We report ten new patients with CSNK2B-related Neurodevelopmental Syndrome associated with heterozygous variants of CSNK2B. In three patients, a pathogenic variant was inherited from an affected parent. We describe both molecular and clinical features, focusing on epileptic and neurodevelopmental phenotypes. The median age at follow-up was 8.5 years (range 21 months-42 years). All patients had epilepsy, with onset at a median age of 10.5 months range 6 days-10 years). Seizures were both focal and generalized and were resistant to anti-seizure medications in two out of ten patients. Six patients had mild to moderate cognitive delays, whereas four patients had no cognitive disability. Although all previously reported patients had a de novo CSNK2B pathogenic variant, here we report, for the first time, two familial cases of CSNK2B-related Neurodevelopmental Syndrome. We confirmed the highly variable expressivity of the disease among both interfamilial and intrafamilial cases. Furthermore, this study provides information about the long-term outcome in adult patients and underlines the importance of detailed family history collection before performing genetic testing in patients with epilepsy and neurodevelopmental disorders.

Insights into cognitive and behavioral comorbidities of SLC6A1-related epilepsy: five new cases and literature review.

Introduction: SLC6A1 pathogenic variants have been associated with epilepsy and neurodevelopmental disorders. The clinical phenotype includes different seizure types, intellectual disability, and psychiatric symptoms affecting mood and behavior. Few data regarding neuropsychological features have been described, and details on cognitive profiles are often missing due to the lack of standardized tests. Methods: We retrospectively reviewed the neuropsychological assessments of five subjects carrying heterozygous missense genetic variants in SLC6A1. We also collected data on epileptic features, EEGs, and brain MRIs. Additionally, we reviewed neuropsychological data from 204 previously reported patients with SLC6A1 pathogenic variants. Results: In our series, at the last evaluation (median 12.6 years), three patients had borderline intellectual functioning, one patient had mild cognitive impairment, and one patient presented with a moderate cognitive disability. Three out of five patients underwent at least two neuropsychological evaluations, which revealed a worsening of cognitive functions over time. We detected attention deficits in all patients. In addition, we observed anxiety, disruptive behavior disorder, emotional instability, and hetero aggressiveness. We also performed a literature review that highlighted that most of the patients with SLC6A1 pathogenic variants have mild-to-moderate intellectual disability and that one-third of cases have autistic traits. Discussion: Based on the literature review and the detailed description of our cases, we conclude that patients with SLC6A1-related epilepsy mostly present with mild-to-moderate intellectual disability, often associated with attention disorders. Such symptoms may worsen over time. Periodic standardized neuropsychological tests may be useful tools to follow development over time, and patient-specific rehabilitation programs could be tailored consistently.

Cross-Cultural Adaptation and Preliminary Validation of Upper Limb Lymphedema Quality of Life Questionnaire (ULL-27) in Italian Female Patients with Breast Cancer-Related Lymphedema.

Purpose: Lymphedema is one of the most recurrent problems reported by breast cancer survivors, which negatively affects quality of life (QoL). The Upper Limb Lymphedema Quality of Life Questionnaire (ULL-27) is a tool that assesses the QoL in patients with breast cancer-related lymphedema. At present, an Italian adaptation does not exist. The aim of this study is to perform a preliminary cross-cultural validation of the Italian version of the ULL-27. Materials and Methods: A forward-backward translation and cross-cultural adaptation have been performed. One hundred twenty women with lymphedema were evaluated using the Italian version of the ULL-27. The mean age was 60.25 (±11.88) years, and mean body-mass index was 26.35 (5.13) kg/m2. The Functional Assessment of Cancer Therapy-Breast (FACT-B) was analyzed using Pearson's correlation analysis with the ULL-27 to indicate convergent and external construct validity. Cronbach's alpha and factor analysis were used to assess the questionnaire's structure. Results: The internal consistency for the total score of the Italian ULL-27 was high (0.90). Content validity was good because items were understandable for all participants. The alpha coefficients for subscale scores were high. External construct validity was confirmed by expected correlations with comparator scales. However, the factor structure of ULL-27 does not seem to completely reflect the original scale. Conclusions: The Italian version of ULL-27 has good internal consistency and validity. It is a reliable tool for evaluating the QoL of these patients, but additional data should be collected to clarify the factorial structure and test-retest reliability of the scale.