ZMYND11 was first reported in relation to autism in 2012 (Iossifov et al PMID:22542183), and in relation to an autosomal dominant syndromic complex disorder in 2014 (Coe et al PMID:25217958, Cobben et al PMID:25281490). Commonly reported features include developmental delay/intellectual disability, seizures, autistic behaviors, delayed speech and language development, behavioral issues (ADHD and aggressive behavior), dysmorphic facies (broad nose, thin lips, low set or posteriorly rotated ears, hypertelorism or deeply set eyes), and hand, foot, and digital abnormalities. Phenotypic features and severity are variable between probands. Twenty-five heterozygous predicted null, loss of function variants and 11 missense variants have been reported in 11 publications and are included in this curation (PMIDs: 34216016, 27626064, 22542183, 25217958, 25281490, 28933030, 32097528, 31337854, 38397245, 29158550, 35172867). The maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is most likely haploinsufficiency. This gene-disease relationship does not have supporting experimental evidence.
In summary, there is definitive evidence supporting the relationship between ZMYND11 and autosomal dominant syndromic complex neurodevelopmental disorder. This has been repeatedly demonstrated in the clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism GCEP on March 28, 2024 (SOP 10).
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.