Pathogenic variants in chromatin‐related genes: Linking immune dysregulation to neuroregression and acute neuropsychiatric disorders

We report eight children with de novo pathogenic DNA variants in chromatin‐related genes: MORC2, CHD7, KANSL1, KMT2D, ZMYND11, HIST1HIE, EP300, and KMT2B. All children experienced infection or vaccine‐provoked neuroregression or abrupt‐onset neuropsychiatric syndromes. Most had delayed development (n = 6) before the first regression, and four had immune deficiency or autoimmunity (n = 4). At a mean age of 4 years 2 months (range 1–8 years), symptoms included infection‐provoked autistic/language regression (n = 6), cognitive decline (n = 3), gait deterioration (n = 3), or abrupt‐onset anxiety, obsessive‐compulsive disorder, and/or tics (n = 5). Three children had ongoing infection‐provoked deteriorations. Six children benefited from intravenous immunoglobulin (n = 3) or antibiotics (n = 4). Ribonucleic acid expression of the eight chromatin genes was similar in neuronal, glial, and peripheral leukocytes, unlike non‐chromatin neurodevelopmental genes, which have predominantly neuronal expression. These cases demonstrate the role of chromatin dysregulation in autistic regression and abrupt‐onset neuropsychiatric syndromes, potentially related to brain and immune gene dysregulation.