Chronic pain in Noonan Syndrome: A previously unreported but common symptom

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 12; pp. 2998 - 3005
• Main Authors: Vegunta, Sravanthi, Cotugno, Richard, Williamson, Amber, Grebe, Theresa A.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Child; Child, Preschool; chronic pain; Chronic Pain - etiology; Chronic Pain - genetics; climate; Female; genotype-phenotype correlations; growth hormone; Growth Hormone - therapeutic use; Humans; joint hypermobility; Male; medical genetics; Middle Aged; Mutation; Noonan syndrome; Noonan Syndrome - drug therapy; Noonan Syndrome - etiology; Noonan Syndrome - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics; Ras-dependent mitogen-activated protein kinase kinase kinase; Surveys and Questionnaires; Young Adult; chronic pain; medical genetics; Noonan syndrome; Ras-dependent mitogen-activated protein kinase kinase kinase; genotype-phenotype correlations; joint hypermobility; climate; growth hormone
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37337

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. © 2015 Wiley Periodicals, Inc.