Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients

Abstract

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio-facio-cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r-FLACC, Wang-Baker scale, NPSI, BPI, NCCPC-R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs-QL, SF-36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscleskeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level. K E Y W O R D S cardiofaciocutaneous syndrome, costello syndrome, Noonan syndrome, pain, RASopathies

Impact of Costello syndrome on growth patterns

“…After 3-5 years, all acquire full oral abilities. Based on our clinical experience we speculate this could be due to improvement of oral over-sensitivity (Leoni et al, 2019) and foregut enteral nervous system maturation, as already hypothesized by Shah, Rodriguez, Louis, Lindley, and Milla (1999).…”

Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status

“…Interestingly, both Johnson's and our study did not detect a signi cant difference in the comfort and pain domains between syndromic patients and normative values. We believe that parents' report could represent a crucial bias, since detection of pain in patients with intellectual disability is quite challenging [25]. On the same way, the absence of signi cant differences between happiness domain in CS vs normative values could be related to the friendly behavior shown by patients with CS [26].…”

Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

“…Secondary experiences of medical involvement, such as pain interference, however, may have a more robust association with emotional symptoms in adolescents with NF1 (Wolters et al, 2015). We did not directly measure the extent of pain, but this is an area that is receiving increasing recognition as a problem interfering with quality of life in individuals with RASopathies (Leoni et al, 2019;Wolkenstein, Zeller, Revuz, Ecosse, & Leplege, 2001;Wolters et al, 2015), and should be examined more closely in future research.…”