Review of disrupted sleep patterns in Smith-Magenis syndrome and normal melatonin secretion in a patient with an atypical interstitial 17p11.2 deletion

• Published in: American journal of medical genetics. Part A Vol. 149A; no. 7; pp. 1382 - 1391
• Main Authors: Boudreau, Eilis A., Johnson, Kyle P., Jackman, Angela R., Blancato, Jan, Huizing, Marjan, Bendavid, Claude, Jones, MaryPat, Chandrasekharappa, Settara C., Lewy, Alfred J., Smith, Ann C.M., Magenis, R. Ellen
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2009; Wiley-Liss; Wiley
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - metabolism; array CGH; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 17; Complex syndromes; Development Biology; Female; Genetics; Humans; Intellectual Disability - complications; Intellectual Disability - genetics; interstitial deletion 17p11.2; Life Sciences; Medical genetics; Medical History Taking; Medical sciences; melatonin; Melatonin - metabolism; Retrospective Studies; sleep; Sleep Initiation and Maintenance Disorders - complications; Sleep Initiation and Maintenance Disorders - diagnosis; Sleep Initiation and Maintenance Disorders - genetics; Smith-Magenis syndrome; Syndrome; Young Adult; Chromosomal aberration; Human; Smith-Magenis syndrome; Melatonin; array CGH; Secretion; Patient; Review; interitial deletion 17p11.2; Normal; Sleep; Malformation; Smith―Magenis syndrome; Deletion; Atypical; Interstitial; Complex syndrome; Bibliographic review; Pineal hormone
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32846

Smith–Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body's signal for nighttime darkness. Published reports of 24‐hr melatonin secretion patterns in two independent SMS cohorts (US and France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion (∼6Mb; cen<‐>TNFRSFproteinB) of chromosome band (17)(p11.2p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern. © 2009 Wiley‐Liss, Inc.