TY - JOUR
T1 - Contrasting painless and painful phenotypes of pediatric restless legs syndrome : a twin family study
AU - Champion, David
AU - Bui, Minh
AU - Aouad, Phillip
AU - Sarraf, Sara
AU - Donnelly, Theresa
AU - Bott, Aneeka
AU - Chapman, Cindy
AU - Goh, Shuxiang
AU - Ng, Georgia
AU - Jaaniste, Tiina
AU - Hopper, John
PY - 2020
Y1 - 2020
N2 - Objective: This study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders. Methods: In a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets. Results: Data were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04). Conclusions: Pediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS.
AB - Objective: This study was designed to investigate painless and painful subsets of pediatric restless legs syndrome (RLS) for genetic influence and for associations with iron deficiency and common pediatric pain disorders. Methods: In a twin family study, twins (3–18 years) and their oldest siblings, mothers and fathers completed questionnaires, assessing lifetime prevalence of RLS using current criteria, as well as history of iron deficiency and pediatric pain disorders. Subsets were categorized as RLS-Painless or RLS-Painful. Within twin pair analyses were conducted to assess familial and potential genetic effects for the defined subsets. Penalized maximum likelihood logistic regression was used to test familial associations. Random-effects logistic regression modeling was used in the total pediatric sample to investigate univariate and multivariate associations with the subsets. Results: Data were available for 2033 twin individuals (1007 monozygous (MZ), 1026 dizygous (DZ); 51.7% female), 688 siblings, 1013 mothers and 921 fathers. Odds ratios, correlations and casewise concordance were significantly higher in MZ than in DZ twins only for RLS-Painful. RLS-Painless, though familial (co-twin and mother), was not genetically influenced, but was independently associated with female sex (OR 0.52, p = 0.003), iron deficiency (OR 4.20, p < 0.001) and with persistent pain disorders (OR 2.28, p = 0.02). RLS-Painful was familial and was probably genetically influenced; was independently associated with non-migraine headaches (OR 2.70, p = 0.02) and recurrent abdominal pain (OR 2.07, p = 0.04). Conclusions: Pediatric RLS was heterogeneous and was categorized into contrasting painless and painful phenotypes. RLS-Painless was associated with iron deficiency while RLS-Painful accounted for the heritability of RLS.
UR - https://hdl.handle.net/1959.7/uws:64828
U2 - 10.1016/j.sleep.2020.08.024
DO - 10.1016/j.sleep.2020.08.024
M3 - Article
SN - 1389-9457
VL - 75
SP - 361
EP - 367
JO - Sleep Medicine
JF - Sleep Medicine
ER -