PotockiLupski

Potocki-Lupski syndrome, also called 17p11.2 duplication syndrome, is a microduplication syndrome characterized by a duplication of the distal portion of chromosome 17p11.2. It was described by Potocki and Lupski in 1996. Most cases arise de novo, but a minority are inherited from a parent carrying the same duplication. The duplicated region typically spans about 3.7 to 5.3 megabases and includes the RAI1 gene, a dosage-sensitive regulator of development.

Clinical features include hypotonia in infancy, feeding difficulties, and global developmental delay with delays in speech and motor skills. Behavioral differences such as attention problems and features overlapping with autism spectrum disorders are common. Minor facial dysmorphism and ear anomalies may be present. Some individuals have congenital heart defects, skeletal issues such as scoliosis, and vision or hearing problems. Phenotype is highly variable.

Diagnosis is usually made by chromosomal microarray analysis, which detects the 17p11.2 duplication, with confirmatory testing by FISH or other methods. Molecular testing can also determine the size and gene content of the duplication, aiding prognosis and counseling. PTLS is distinct from, but related to, Smith-Magenis syndrome, which results from a deletion of the same 17p11.2 region.

Management is multidisciplinary, including developmental therapies, speech and language therapy, physical therapy, and monitoring for cardiac, orthopedic, and sensory issues. Early intervention can improve communication and motor outcomes. Genetic counseling addresses recurrence risk, which is generally low for de novo cases but nonzero if a parent carries the duplication.