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.
Keywords: Potocki-Lupski syndrome; duplication 17p11.2; sleep.
© 2019 Wiley Periodicals, Inc.
Conflict of interest statement
DECLARATION of INTERESTS:
Kevin Kaplan: no conflicts of interest
Caroline McCool: No conflicts of interest
James R. Lupski: Baylor College of Medicine (BCM) and Miraca Holdings have formed a joint venture with shared ownership and governance of the Baylor Genetics (BG), which performs clinical microarray analysis and clinical exome sequencing. J.R.L. serves on the Scientific Advisory Board of the BG. J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron pharmaceuticals, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Genetics Laboratories.
Daniel Glaze: No conflicts of interest
Lorraine Potocki: The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from molecular genetic testing offered in the Baylor Genetics Laboratories.
RAI1 Overexpression Promotes Altered Circadian Gene Expression and Dyssomnia in Potocki-Lupski SyndromeSV Mullegama et al. J Pediatr Genet 6 (3), 155-164. PMID 28794907.Retinoic acid induced 1 ( RAI1 ) encodes a dosage-sensitive gene that when haploinsufficient results in Smith-Magenis syndrome (SMS) and when overexpressed …
The Behavioural Phenotype of Potocki-Lupski Syndrome: A Cross-Syndrome ComparisonS Bissell et al. J Neurodev Disord 10 (1), 2. PMID 29329513.Findings suggest some overlap in the behavioural phenotype of PTLS and features of ASD symptomatology; however, the overall profile of behaviours in PTLS appears to be di …
Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients With Smith-Magenis Syndrome and Potocki-Lupski SyndromeCG Lee et al. J Korean Med Sci 27 (12), 1586-90. PMID 23255863. - Case ReportsDeletion and duplication of the -3.7-Mb region in 17p11.2 result in two reciprocal syndrome, Smith-Magenis syndrome and Potocki-Lupski syndrome. Smith-Magenis syndrome is …
Neurodevelopmental Disorders Associated With Abnormal Gene Dosage: Smith-Magenis and Potocki-Lupski SyndromesJ Neira-Fresneda et al. J Pediatr Genet 4 (3), 159-67. PMID 27617127. - ReviewSmith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 M …
Inherited dup(17)(p11.2p11.2): Expanding the Phenotype of the Potocki-Lupski SyndromePL Magoulas et al. Am J Med Genet A 164A (2), 500-4. PMID 24311450. - ReviewPotocki-Lupski syndrome (PTLS, OMIM: 610883) is a microduplication syndrome characterized by infantile hypotonia, failure to thrive, cardiovascular malformations, develop …
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