Objective measures of sleep disturbances in children with Potocki–Lupski syndrome

Abstract

Potocki-Lupski syndrome (PTLS; MIM 610883) is a neurodevelopmental disorder caused by a microduplication, a 3.7 Mb copy number variant, mapping within chromosome 17p11.2, encompassing the dosage-sensitive RAI1 gene. Whereas RAI1 triplosensitivity causes PTLS, haploinsufficiency of RAI1 due to 17p11.2 microdeletion causes the clinically distinct Smith-Magenis syndrome (SMS; MIM 182290). Most individuals with SMS have an inversion of the melatonin cycle. Subjects with PTLS have mild sleep disturbances such as sleep apnea with no melatonin abnormalities described. Sleep patterns and potential disturbances in subjects with PTLS have not been objectively characterized. We delineated sleep characteristics in 23 subjects with PTLS who underwent a polysomnogram at Texas Children's Hospital. Eleven of these subjects (58%) completed the Child's Sleep Habits Questionnaire (CSHQ). Urinary melatonin was measured in one patient and published previously. While the circadian rhythm of melatonin in PTLS appears not to be disrupted, we identified significant differences in sleep efficiency, percentage of rapid eye movement sleep, oxygen nadir, obstructive apnea hypopnea index, and periodic limb movements between prepubertal subjects with PTLS and previously published normative data. Data from the CSHQ indicate that 64% (7/11) of parents do not identify a sleep disturbance in their children. Our data indicate that younger individuals, <10 years, with PTLS have statistically significant abnormalities in five components of sleep despite lack of recognition of substantial sleep disturbances by parents. Our data support the contention that patients with PTLS should undergo clinical evaluations for sleep disordered breathing and periodic limb movement disorder, both of which are treatable conditions. K E Y W O R D S duplication 17p11.2, Potocki-Lupski syndrome, sleep

Neurological phenotype of Potocki–Lupski syndrome

“…In some patients sleep anomalies can be less apparent and manifests in subtler ways, such as daytime sleepiness (Kaplan, McCool, Lupski, Glaze, & Potocki, 2019). It is essential to monitor similar symptoms, as they could also be the only hint of a significant sleep breathing disorder, that is reported to be present in as much as 60% of PLS children below 10 years of age (Kaplan et al, 2019); such data do not find a confirmation in our study, as a night-time breathing problem was suspected in two children, but in both of them the nocturnal polysomnography resulted to be normal.…”