Potocki-Lupski Syndrome (PTLS)

Potocki-Lupski Syndrome (PTLS) is a disorder caused by a duplication of the 17p11.2 region of chromosome 17, including the RAI1 (Retinoic acid-induced protein 1) gene. Duplication of the RAI1 gene in particular is thought to be the key contributor to the symptoms of this disorder. These symptoms are vast and include cognitive, behavioral, and medical issues. The prevalence of PTLS is about one in every 25,000 people. This duplication is reciprocal to deletion of this area, causing Smith-Magenis syndrome.

Individuals with PTLS typically have developmental delay, intellectual disability (ID), attention issues, hyperactivity, anxiety, and in some cases, autism spectrum disorder. Medically, issues can include hypotonia (weak muscle tone), oropharyngeal dysphagia (difficulty or abnormality in swallowing),congenital heart disease, sleep apnea, low blood sugar, and dysmorphic facial features. Management of these symptoms depends on severity, but patients should be monitored for developmental and behavioral issues as they grow. While this duplication typically occurs spontaneously and is not inherited, genetic counseling is recommended to determine the cause, especially if the family is planning on having more children.

The diagnosis of this disorder is established only after a genetic test confirms duplication in the 17p11.2 region that includes the RAI1 gene. Approximately two-thirds of individuals with PTLS have a duplication spanning 3.7Mb. The other one-third have duplications (that include RAI1) spanning 0.4Mb-19.7Mb. Yuan-Harel-Lupski syndrome (duplication in 17p12-p11.2 that includes both RAI1 and PMP22 genes) is close to PTLS. It has similar symptoms as PTLS, but with the addition of peripheral neuropathy (caused by the PMP22 duplication).

Potocki et al. “Potocki-Lupski Syndrome”. GeneReviews. 2017.