Linkage analysis was performed in a four-generational German family with restless legs syndrome (RLS) affecting 15 of 37 family members, in a study at the University of Lubeck, Germany. Age at onset was in early childhood or adolescence in 9 (60%) cases. Clinical findings included a desire to move the legs, paresthesias, motor restlessness at night resulting in sleep disturbance and daytime fatigue. Several family members had severe psychiatric problems, including depression and personality disorder. The inheritance pattern was autosomal dominant. A new RLS gene locus (RLS3) was identified on chromosome 9 in all of 12 patients tested, and 11 of these carried an additional closely linked RLS locus. 
COMMENT. A linkage to a new locus (RLS3) on chromosome 9p has been identified in a family with RLS of early onset. Five gene loci have previously been mapped in cases of primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p. To date, no gene mutation has been found. RLS is primary or secondary. The primary form is highly familial; secondary RLS is often associated with iron deficiency, renal disease, or pregnancy. The pathophysiology may be related to dopamine insufficiency and low iron storage in substantia nigra.