Childhood-onset restless legs syndrome: Clinical and genetic features of 22 families

• Published in: Movement disorders 2008-06, Vol.23 (8), p.1113-1121
• Main Authors: Muhle, Hiltrud, Neumann, Anja, Lohmann-Hedrich, Katja, Lohnau, Thora, Lu, Yang, Winkler, Susen, Waltz, Stephan, Fischenbeck, Anke, Kramer, Patricia L., Klein, Christine, Stephani, Ulrich
• Format: Article
• Language: English
• Subjects: Adolescent; Age of Onset; Alleles; Attention Deficit Disorder with Hyperactivity - diagnosis; Biological and medical sciences; Child; Child, Preschool; children; Chromosome Aberrations; Chromosome Mapping; clinical course; Diagnosis, Differential; Female; Genes, Dominant - genetics; Genetic Predisposition to Disease - genetics; genetics; Genotype; Haplotypes; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Male; Medical sciences; Microsatellite Repeats; Nervous system (semeiology, syndromes); Neurology; Pedigree; Polymorphism, Single Nucleotide - genetics; Restless legs syndrome; Restless Legs Syndrome - diagnosis; Restless Legs Syndrome - genetics
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.22016

Restless legs syndrome (RLS) is a sensory‐motor disorder that is underdiagnosed in children and often misclassified as attention deficit hyperactivity disorder. Five different gene loci (RLS1‐5) and three susceptibility loci have been identified in adult‐onset RLS. We included 23 children with RLS (age at onset ≤14 years) from 22 families. In 14 families, we performed linkage and genotype analyses. Of the 23 RLS patients, only seven (30.4%) were admitted for a suspected diagnosis of RLS. Five patients had a retrospectively established onset at an age as early as 1 year. The most frequent complaint in patients were sleep problems (21 of 23; 91%) resulting in fatigue in 14 children (60.9%). Twelve of the 19 tested cases (63.2%) exhibited an index of periodic limb movements in sleep greater than 5. Dopaminergic therapy was successful in 12 of 14 treated patients (85.7%). Family history for RLS was positive in 20 of 23 children (87.0%) and compatible with an autosomal dominant inheritance pattern. Linkage analysis excluded all five loci in two families. A trend for an association at two of the three reported susceptibility regions was observed. RLS symptoms can occur in early childhood. The positive family history suggests a genetic cause in most families with at least one additional RLS gene locus. © 2008 Movement Disorder Society