The 15q11.2 microdeletion syndrome, also known as Burnside-Butler syndrome (BBS), is a rare genetic disorder involving a deletion in the breakpoint 1 to breakpoint 2 (BP1-BP2) on the long arm of chromosome 15, often associated with growth retardation and delayed speech development. In contrast, rare manifestations consist of dysmorphic traits, seizures, and neurodevelopmental or psychiatric conditions such as epilepsy, autism spectrum disorder (ASD), and schizophrenia. The BP1-BP2 region contains genes critical for brain development and function, including non-imprinted in Prader-Willi/Angelman syndrome 1 (NIPA1), non-imprinted in Prader-Willi/Angelman syndrome 2 (NIPA2), cytoplasmic FMR1 interacting protein 1 (CYFIP1), and tubulin gamma complex associated protein 5 (TUBGCP5), which have been linked to conditions such as attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and epilepsy. Prenatal tests and karyotype lead to unclear results, but the current chromosomal microarray analysis (CMA) provides an accurate diagnosis of BBS. Treatment for these individuals is personalized and typically involves a multidisciplinary approach. We present the case of a six-year-old male patient with 15q11.2 microdeletion syndrome and a complex neurological and developmental profile, including developmental delay and ASD. We highlight the rare combination of early-onset refractory epilepsy, schizencephaly, and cystic fibrosis transmembrane conductance regulator (CFTR) variant carrier status, which adds to the uniqueness of the case. This article contributes to expanding the clinical spectrum of 15q11.2 microdeletion syndrome. It underscores the importance of genetic testing in children with complex neurodevelopmental symptoms, as the clinical presentation of this syndrome is often subtle or nonspecific, making early diagnosis and genetic counseling challenging but essential for guiding appropriate interventions.

15q11.2 microdeletion can lead to syndromes affecting the nervous system. However, 15q11.2 microdeletion has large phenotypic differences and incomplete penetrance, which brings challenges to prenatal diagnosis. We reported 21 cases of 15q11.2 microdeletion fetuses in Eastern China and reviewed literature on the prenatal clinical characteristics related to the deletion variants to provide a basis for prenatal genetic counseling. The clinical data of 21 cases of 15q11.2 microdeletion fetuses collected from June 2018 to September 2021 were retrospectively analyzed, and chromosomal microarray analysis was performed. The reported prenatal clinical features of 15q11.2 microdeletion fetuses were reviewed and summarized. A meta-analysis of 20 studies was performed to test heterogeneity, data integration, and sensitivity on the correlation between 15q11.2 microdeletion and neuropsychiatric diseases. The median age of the women was 29.5 years. The median gestational age at interventional examination was 24 weeks. All fetuses showed deletion variants of the 15q11.2 fragment, and the median deletion range was approximately 0.48 MB. Ultrasound of five cases showed no abnormalities; however, four of them showed a high risk of Down's syndrome (risk values were 1/184, 1/128, 1/47, and 1/54, respectively). The remaining 16 fetuses showed congenital heart disease (7/16), elevated nuchal translucency (5/16), abnormal brain structure (2/16) and renal disease (2/16). In a literature review of 82 prenatal cases, 44% (36/82) had abnormal ultrasound features, 31% (11/36) showed abnormal nuchal translucency, approximately 28% (10/36) showed abnormal cardiac structure, and 14% (5/36) had brain structural abnormalities. The meta-analysis revealed that the frequency of the 15q11.2 microdeletion mutation in patients with schizophrenia and epilepsy was significantly higher (odds ratio 2.04, 95% confidence interval: 1.78-2.33, p < 0.00001; odds ratio 5.23, 95% confidence interval: 2.83-9.67, p < 0.00001) than that in normal individuals. More than half of the 15q11.2 microdeletion cases presented no abnormalities in prenatal ultrasound examination. The cases with ultrasound features mainly showed isolated malformations such as elevated nuchal translucency, congenital heart disease, and brain structural abnormalities. Postpartum 15q11.2 microdeletion patients are at an increased risk of suffering from schizophrenia, epilepsy, and other neurological and mental diseases from 15q11.2 microdeletion. Therefore, prenatal diagnosis of 15q11.2 microdeletion not only depends on molecular diagnostic techniques but also requires cautious genetic counseling.

Burnside Butler syndrome or 15q11.2 microdeletion syndrome is a relatively rare chromosomal abnormality that is recently being recognized. Current diagnostic techniques like chromosomal microarray analysis (CMA) have profoundly contributed to currently reported cases. The diagnostic dilemma is that prenatal screening and karyotype analysis typically yield unclear results. We would like to emphasize the importance of taking a detailed family history, knowing the classic clinical features, and using CMA to help diagnose this syndrome. We present an eight-year-old Caucasian female with a past medical history of intrauterine growth restriction, microcephaly, a high arched palate, speech delay, and a learning disability with recurrent bleeding from the eyes and oral cavity. The bleeding co-occurs whenever she develops the common cold.