Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome

Abstract

Idiopathic restless legs syndrome (RLS) frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. We describe the largest German kindred of familial RLS with 20 affected and investigated members in four generations with a variety of clinical symptoms. Patients were examined clinically, and polysomnography was performed in selected cases. The diagnosis was set according to the diagnostic criteria of the International RLS Study Group. All patients showed sensory symptoms of their legs and a worsening of symptoms with increasing age. Older patients, who needed treatment, responded well to opioids. Segregation ratios were close to 0.5, confirming a virtually complete penetrance. The mean age of onset fell from 51.5 years in the second generation to 19.8 years in the fourth generation (ANOVA, p = 0.025). The identification of presymptomatic carriers in the fourth generation in the following years, however, may prejudice this result. This large family showed the variety of clinical RLS symptoms with decreasing age of onset in generations II-IV, suggesting at least the possibility of anticipation.

Restless legs syndrome

“…4,5 There are several reports of RLS occurring in families, which suggest an autosomal dominant mode of inheritance with variable expression and possible anticipation as there was evidence for an earlier age at onset in later generations. [6][7][8] Secondary RLS occurs as a result of certain conditions and the three major reversible causes are iron deficiency anaemia, pregnancy and end-stage renal disease. 9,10 Other secondary causes include vitamin B12/folate deficiency, peripheral neuropathy (associated with diabetes mellitus), rheumatoid arthritis, spinal disorders such as spinal nerve root irritation, Parkinson's disease, fibromyalgia, spinocerebellar ataxia (particularly SCA 3) and Charcot-Marie-Tooth disease (type 2).…”

Restless legs syndrome: an unusual cause for a perplexing syndrome

“…2,5 Associated features include sleep disturbance due to periodic limb movements in sleep (PLMS); dyskinesias, and a family history suggesting autosomal dominant inheritance. 6 RLS is associated with a variety of medical conditions, neurological disorders, and vascular problems and insu ciency. 5,7,8 Among the more frequent conditions are anemias, blood dyscrasias, uremia, myelopathies and neuropathies.…”

Restless Legs Syndrome

“…Occasionally, remissions may occur in which the symptoms decrease signi®cantly or cease for a period of time but more often symptoms remain and worsen. 4,9,10 The incidence of RLS in pregnancy, usually in the second half of gestation, can be as high as 11% to 27%. 5,11,12 The symptoms often appear initially during pregnancy and after delivery may disappear for many years.…”

“…4,19 Electromyogram (EMG) and nerve conduction studies may document any accompanying peripheral neuropathy or radiculopathy. 10,14 Electrophysiological testing in primary RLS patients suggests that polyneuropathy is of an axonal nature. 40 Based on morphometric analysis of sural nerves which showed a signi®cant reduction in myelinated ®ber density, Iannacone et al 54 suggested that axonal neuropathy is often present in patients with primary RLS.…”