Background <p>Contactin-associated protein-like 2 (CASPR2) antibody-related neurological syndrome is well defined in adults, while data in children is rare. We perform this case series and literature review to ascertain the clinical features of this disorder in children.</p> Case presentations <p>We describe three cases who were diagnosed with CASPR2 antibody-related neurological syndrome, and then systematically characterized clinical features, therapeutic responses, and outcomes in 64 patients in literature. Among the 67 patients, the median age was 8.4 years (range 0.5–18), with a male predominance (65.7%). The most characteristic symptoms of CASPR2 antibody-related neurological syndrome include psychiatric abnormalities (68.7%), sleep disorders (55.2%), dysautonomia (44.8%), movement disorders (43.3%), seizures (41.8%), neuropathic pain (34.3%), and cognitive disturbances (31.3%). Autoimmune encephalitis (AE, 62.7%) was most frequent, followed by Morvan syndrome (MoS, 26.9%) and peripheral nerve hyperexcitability (PNH, 7.5%). CASPR2 antibodies are typically detected in serum (85.1%), but rarely in CSF exclusively (3.0%). Investigations revealed abnormalities in CSF analysis (22.9%; 13 AE, 5 MoS), brain MRI (24.1%; 11 AE, 3 MoS), and EEG (67.3%; 26 AE, 7 MoS). Neoplasm was not found in our case series and literature review. Regarding treatment, 46 patients received first-line immunotherapy alone, while 5 required second-line treatment. Immunotherapy demonstrated highly effective, with 95.8% achieving a favorable outcome (mRS score ≤ 2) and a low recurrence rate of 5.1%.</p> Conclusions <p>We therefore recommend that all children presenting with new-onset psychiatric abnormalities, sleep disorders, dysautonomia, movement disorders, seizures, neuropathic pain, and cognitive disturbances should be suspected of having CASPR2 antibody-related neurological syndrome. Neoplastic processes are rare in pediatric patients. Early recognition of the disease is important because it responds well to immunotherapy.</p>