A Sadhwani1, J M Willen2,3, H Miller2,4, R Barbieri-Welge5, L T Horowitz6, L M Noll7, S Peters8, R Hundley8, L M Bird9, W H Tan2. 1. Department of Psychiatry, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA. 2. Division of Genetics & Genomics, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA. 3. Department of Psychiatry, Kennedy Krieger Institute, Baltimore, MD, USA. 4. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 5. Developmental Evaluation Clinic, Rady Children's Hospital San Diego, San Diego, CA, USA. 6. Greenwood Genetic Center, Greenwood, SC, USA. 7. Psychology Service, Texas Children's Hospital, Houston, TX, USA. 8. Division of Developmental Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 9. University of California, San Diego, Department of Pediatrics and Genetics/Dysmorphology, Rady Children's Hospital San Diego, San Diego, CA, USA.
Abstract
BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar. METHODS: Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings. RESULTS: Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups. CONCLUSIONS: The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.
BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar. METHODS: Through an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings. RESULTS: Second-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups. CONCLUSIONS: The presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.
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