关键词: SETBP1基因, 发育障碍, 功能缺失变异, 单倍剂量不足

Abstract:

Objective To summarize the clinical phenotype and genetic variation characteristics of patients with SETBP1 haploinsufficiency disorder (SETBP1-HD). Methods The genetic variations and clinical characteristics of three children with SETBP1-HD from January 2019 to December 2021 were retrospectively analyzed. Results Three SETBP1-HD children, 1 boy and 2 girls (identical twins), were 5 years old and 5 months old respectively. All patients presented moderate intellectual disabilities, motor and language developmental retardation. Compared with the verbal expression ability, the language comprehension ability of case 1 was better, and the child also had attention deficits. Case 2 and case 3 had febrile seizures. No obvious autism-like manifestations were observed in the 3 cases, and no specific manifestations were observed on head MRI scan and video electroencephalogram. De novo heterozygous variations in SETBP1 gene were found in all patients, including a frameshift variation (c.607delG/p.Gly203Valfs*4) from case 1 and a nonsense variation (c.1873C>T/p.Arg625*) from case 2 and case 3. Conclusions SETBP1-HD is a different phenotype from Schinzel-Giedion syndrome. The main clinical features of SETBP1-HD are intellectual disabilities, speech and language disorder, and motor developmental retardation. Speech and language disorders are the core symptoms of the disease. Some patients may have behavioral problems and convulsive seizures. Loss of function variation in SETBP1 resulting in haploinsufficiency is the cause of this disease. Patients can benefit partially from supportive treatment such as rehabilitation training, behavioral therapy, and anticonvulsant medication. Prenatal diagnosis is an important measure to prevent this disease.

Key words: SETBP1 gene, developmental disorder, loss of function variation, haploinsufficiency