Introduction: Obsessive-compulsive disorder (OCD) has a relevant polygenic contribution (1). Secondary forms of obsessive-compulsive symptoms (OCS) are associated with therapy resistance (2,3) and might be caused by rare copy number variants (CNVs) (4-6). A recent study analyzing CNVs in 2,248 OCD cases and 3,608 controls identified a significant increase in the burden of large CNVs in the OCD group without a specific locus (6). The rationale of this article is to describe a paradigmatic case with OCS and a possibly underlying microduplication of the RB1CC1 (also known as FIP200) gene with signs of brain involvement detected via magnetic resonance imaging (MRI). Methods: The diagnostic workup, including laboratory, magnetic resonance imaging (MRI), and electroencephalography (EEG) analyses, was carried out according to the Freiburg diagnostic protocol for OCD (7). Psychometric testing included a test battery with questionnaires for OCD (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] (8) and Obsessive-Compulsive Inventory-Revised [OCI-R]) (9), attention deficit hyperactivity disorder (ADHD), and autism. Neuropsychological testing comprised the Wechsler Adult Intelligence Scale (10) and Test of Attentional Performance (11). Genetic testing comprised cytogenetic analyses (conventional karyotyping) and molecular karyotyping using array-comparative genomic hybridization (aCGH) via CytoSure Constitutional microarray (OGT/Sysmex, Oxford, United Kingdom). Clinical exome sequencing was performed using enrichment with the Twist Human Core Exome Kit (Twist Bioscience, San Francisco, United States) and sequencing on a NextSeq1000 System (Illumina, San Diego, United States). Results: The 31-year-old male patient, who has given his written informed consent for this publication, was admitted to our specialized ward for OCD due to treatment-resistant OCD (Y-BOCS score: 21; OCI-R score: 23). OCS included predominant washing and cleaning compulsions and less prominently aggressive intrusive thoughts that had been chronically present since the age of approximately 15 years. In addition, subsyndromal ADHD and autism symptoms, as well as a intellectual disability (IQ: 63; reference: 85-115), were observed. Dysmorphologies included frontal bossing, short philtrum, high palate, and a single transverse palmar crease. The family history revealed maternal alcohol addiction during pregnancy. The diagnostic work-up revealed a hyperintensity in the right putamen in the susceptibility weighted imaging (SWI) MRI sequence (most likely an indication of microbleed, or possibly calcification or small cavernous malformation) and a slight volume loss in the medulla oblongata in an automated morphometry approach (https://www.veobrain.com/?page=veomorph). Independent component analysis of the electroencephalography found some frontocentral theta activity and no epileptic activity. In addition, a ventricular septal defect (VSD) of the heart and thoracic scoliosis were identified in the transthoracic echocardiography and X-ray, respectively. An external orthopedist diagnosed flat valgus foot. Genetic testing revealed a heterozygous microduplication of the RB1CC1 (FIP200) gene of at least 439.86 kb (position: 8:52470700-52910562, hg38). The karyotype, according to the International System for Human Cytogenomic Nomenclature 2020 (https://iscn.karger.com), was as follows: arr [GRCh38] 8q11.23(52470700_52910562)x3. This microduplication encompasses the entire RB1CC1 (FIP200) gene (RB1-inducible coiled-coil; OMIM *606837) as well as the ALKAL1 (OMIM *619670) gene. Clinical exome analysis did not identify other pathogenic genetic alterations, especially no pathogenic single nucleotide variants. The patient received a combined treatment of sertraline 200 mg (finally reduced to 150 mg because of increased serum levels) and inpatient cognitive behavioral therapy with exposure exercises and response prevention. This treatment resulted in a partial improvement in OCS (Y-BOCS reduction by 57%; OCI-R reduction by 30%).