title: Chronic pain in Noonan Syndrome: A previously unreported but common symptom.
abstract: Noonan syndrome (NS) is a multiple malformation syndrome characterized by pulmonic stenosis, cardiomyopathy, short stature, lymphatic dysplasia, craniofacial anomalies, cryptorchidism, clotting disorders, and learning disabilities. Eight genes in the RAS/MAPK signaling pathway are implicated in NS. Chronic pain is an uncommon feature. To investigate the prevalence of pain in NS, we distributed a two-part questionnaire about pain among NS individuals at the Third International Meeting on Genetic Syndromes of the Ras/MAPK Pathway. The first part of the questionnaire queried demographic information among all NS participants. The second part was completed by individuals with chronic pain. Questions included musculoskeletal problems and clinical features of pain. Forty-five questionnaires were analyzed; 53% of subjects were female. Mean age was 17 (2-48) years; 47% had a PTPN11 mutation. Sixty-two percent (28/45) of individuals with NS experienced chronic pain. There was a significant relationship between prevalence of pain and residing in a cold climate (P = 0.004). Pain occurred commonly in extremities/joints and head/trunk, but more commonly in extremities/joints (P = 0.066). Subjects with hypermobile joints were more likely to have pain (P = 0.052). Human growth hormone treatment was not statistically significant among subjects without chronic pain (P = 0.607). We conclude that pain is a frequent and under-recognized clinical feature of NS. Chronic pain may be associated with joint hypermobility and aggravated by colder climate. Our study is a preliminary investigation that should raise awareness about pain as a common symptom in children and adults with NS.
authors: University of Arizona College of Medicine, Phoenix, Arizona.
authors: Sravanthi
authors: S
authors: Vegunta
authors: Department of Pediatric Pain Management, Phoenix Children's Hospital, Phoenix, Arizona.
authors: Richard
authors: R
authors: Cotugno
authors: Department of Pediatric Pain Management, Phoenix Children's Hospital, Phoenix, Arizona.
authors: Amber
authors: A
authors: Williamson
authors: Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, Arizona.
authors: Theresa A
authors: TA
authors: Grebe
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D059350:Chronic Pain / Q000209:etiology* / Q000235:genetics; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009634:Noonan Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D013006:Growth Hormone; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: Noonan syndrome; Ras-dependent mitogen-activated protein kinase kinase kinase; chronic pain; climate; genotype-phenotype correlations; growth hormone; joint hypermobility; medical genetics