ANKRD11 was reported in relation to autosomal dominant KBG syndrome as early as 2011 (Sirmaci et al., PMID: 21782149). KBG syndrome is characterized by phenotypes including neurological involvement, characteristic facial dysmorphisms, macrodontia, short stature, and hand anomalies. Evidence supporting this gene-disease relationship includes case-level data and experimental data. More than 100 affected individuals have been described in the literature; however, only 9 probands (across 8 publications: 21782149, 25543316, 30088855, 27900361, 27605097, 25424714, 25464108, 28449295) are documented here, as these probands are enough to maximize the genetic evidence score in this rubric. Eight of these probands presented with mild to moderate intellectual disability, two had formal diagnoses of autism spectrum disorder, and 1 additional proband displayed autistic behavior. Six probands had developmental delay ranging from mild to severe; however, it is possible that not all patients were evaluated for this phenotype. While the majority of cases of KBG syndrome occur de novo, variants in ANKRD11 segregated with disease in 8 additional individuals in 3 of these families (PMID: 21782149, 25424714, 25464108). The proposed mechanism of disease is dominant-negative (Walz et al. 2015, PMID: 25413698). This gene-disease association is supported by animal models, expression studies, and in vitro functional assays. In summary, ANKRD11 is definitely associated with autosomal dominant KBG syndrome.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.