Phenotypic description of a large French series of individuals with Potocki-Lupski syndrome

Background Potocki-Lupski syndrome (PTLS) is a rare genetic disorder, with an estimated prevalence of 1:25 000. Detection of a duplication at position 17p11.2 comprising the RAI1 gene establishes the diagnosis. Deletion of this same region is responsible for Smith-Magenis syndrome (SMS). Hitherto, the non-specific clinical features included psychomotor and growth retardation and multiple congenital anomalies. Our aim was to further delineate the clinical spectrum of PLTS. Methods We gathered a series of 56 individuals carrying a 17p11.2 duplication, one of the largest reported to date. We collected detailed phenotypic data and established a phenotypic comparison with individuals already described in the literature. Results We corroborated the main clinical signs associated with PTLS and highlighted additional features present in a significant proportion in our series, such as intrauterine growth retardation or low birth weight, musculoskeletal and ophthalmological anomalies, and abnormalities of the skin appendages. In line with previous reports, behavioural disorders were frequently identified (23%). Yet unexpectedly, self-aggressive and hetero-aggressive behaviours, characteristic features of SMS, were found in a small number of individuals. Forty-six individuals harboured the recurrent duplication (85%), five had larger duplications (9%) and three had smaller duplications (6%). We did not identify inherited duplications when parental information was available (n=43). Conclusion Our study refined the clinical features of PTLS and their relative frequencies. Our findings therefore contribute to improving management of people with PTLS. These open up new pathophysiological hypotheses involving RAI1 gene dosage of the genesis and control of behaviour, as well as new, more complex regulatory pathways.