Periodic limb movements during sleep in Lesch-Nyhan syndrome

To characterize the periodic limb movements during sleep (PLMS) in children with Lesch-Nyhan syndrome (LNS).

Three subjects with LNS aged 2 to 7 years were enrolled. PLMS was diagnosed clinically in one patient, and based on polysomnography (PSG) in two.

Repetitive, clustered movements during sleep, involving upper and lower extremities, were first observed in each child between 1 and 5 years of age, preceding the onset of self-injurious behaviors (SIB) characteristic of LNS. The movement patterns consisted of either flexion, or a combination of flexion and extension, of all four limbs. Duration of muscle contraction ranged from 0.5 to 5 s, with inter-movement intervals generally of 5 to 20 s. PSG qualified these movements as PLMS, by demonstration of four or more movements in clusters, occurring predominantly during N1 sleep stage. The PLMS index was 6.9 and 8.8 events per sleep hour for each patient.

PLMS may represent impaired spinal sensory gating in LNS, potentially resulting from reduced dopaminergic activity and/or dopamine receptor hypersensitivity. We propose that SIB in LNS constitutes a maladaptive motor response to aberrant sensory processing or dysesthesia, arising from dopaminergic imbalance across cortico-striatal, trigeminal, and spinal gating systems.