Assessment of cognitive outcome measures in teenagers with 15q13.3 microdeletion syndrome

Purpose: 15q13.3 microdeletion syndrome causes a spectrum of neuropsychological disorders, including intellectual disability and autism. We aimed to determine if any or all of three neurocognitive tests (the KiTAP, CogState, and Stanford-Binet) were suitable for assessment of cognitive function in affected individuals. Methods: The KiTAP, CogState, and Stanford-Binet tests were administered to ten individuals with 15q13.3 microdeletion syndrome (12-21 years of age), and the results were analyzed to determine feasibility, potential for improvement, and internal consistency. Results: 15q13.3 microdeletion patients were able to complete the components assessed for each of the three tests. Minimal basal and ceiling effects were observed. Patients scored below the 50th percentile on the large majority of test components. Internal consistency was acceptable (≥0.7) for the components assessed. Conclusions: The KiTAP, CogState, and Stanford-Binet are valid tests of cognitive function in 15q13.3 microdeletion patients. These tests may be considered for use as objective outcome measures in future clinical trials, assessing change in neurological function over a period of pharmacological treatment

The expanding clinical phenotype of germline ABL1-associated congenital heart defects and skeletal malformations syndrome.

Congenital heart defects and skeletal malformations syndrome (CHDSKM) is a rare autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive. CHDSKM is caused by germline mutations in ABL1. To date, three variants have been in association with CHDSKM. In this study, we describe three de novo missense variants, c.407C\u3eT (p.Thr136Met), c.746C\u3eT (p.Pro249Leu), and c.1573G\u3eA (p.Val525Met), and one recurrent variant, c.1066G\u3eA (p.Ala356Thr), in six patients, thereby expanding the phenotypic spectrum of CHDSKM to include hearing impairment, lipodystrophy-like features, renal hypoplasia, and distinct ocular abnormalities. Functional investigation of the three novel variants showed an increased ABL1 kinase activity. The cardiac findings in additional patients with p.Ala356Thr contribute to the accumulating evidence that patients carrying either one of the recurrent variants, p.Tyr245Cys and p.Ala356Thr, have a high incidence of cardiac abnormalities. The phenotypic expansion has implications for the clinical diagnosis of CHDSKM in patients with germline ABL1 variants

Assessment of Cognitive Outcome Measures in Teenagers with 15q13.3 Microdeletion Syndrome

15q13.3 microdeletion syndrome causes a spectrum of cognitive disorders, including intellectual disability and autism. We aimed to determine if any or all of three cognitive testing systems (the KiTAP, CogState, and Stanford–Binet) are suitable for assessment of cognitive function in affected individuals. These three tests were administered to ten individuals with 15q13.3 microdeletion syndrome (14–18 years of age), and the results were analyzed to determine feasibility of use, potential for improvement, and internal consistency. It was determined that the KiTAP, CogState, and Stanford–Binet are valid tests of cognitive function in 15q13.3 microdeletion patients. Therefore, these tests may be considered for use as objective outcome measures in future clinical trials, assessing change in cognitive function over a period of pharmacological treatment