Smith-Magenis Syndrome—Clinical Review, Biological Background and Related Disorders

Abstract

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions (90%), encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1), or by pathogenic variants in RAI1 itself (10%). RAI1 is a dosage-sensitive gene expressed in many tissues and acting as transcriptional regulator. The majority of individuals exhibit a mild-to-moderate range of intellectual disability. The behavioral phenotype includes significant sleep disturbance, stereotypes, maladaptive and self-injurious behaviors. In this review, we summarize current clinical knowledge and therapeutic approaches. We further discuss the common biological background shared with other conditions commonly retained in differential diagnosis.

Cerebral Venous Thrombosis in a Patient With Smith-Magenis Syndrome

“…SMS is characterized by distinctive physical features (particularly coarse facial features that progress with age), cognitive impairment, behavioral abnormalities, developmental delay, sleep disturbance, and childhood-onset abdominal obesity. The majority of individuals function in the mildto-moderate range of intellectual disability [1]. SMS is a rare disorder with continuous exploration of multisystemic manifestations.…”

“…SMS is a rare disorder with continuous exploration of multisystemic manifestations. Multisystemic manifestations including cardiovascular (congenital heart defects), genitourinary malformations, ocular (microcornea, strabismus), otolaryngological (sensorineural hearing loss), and malignancy are known [1]. However, hematological manifestations such as venous thrombosis (VT) including cerebral venous thrombosis (CVT) have not been reported to date.…”

Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome

“…The behavioral symptoms include self-inflicted injury and stereotyped movements [ 3 ]. Most SMS patients exhibit neurological symptoms, mild-to-moderate intellectual disability, and strong long-term memory deficits [ 4 ], and almost all (96%) SMS patients also show delayed speech and motor skills [ 4 ], hyperphagia [ 5 ], and sleep disturbance [ 6 ]. Sleep disturbance is one of the earliest diagnostic indicators of SMS and manifests by frequent awakenings during night-time sleep and excessive daytime sleepiness [ 7 ].…”

Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome

“…Behavioral symptoms include self-in icted injury and stereotyped movements 3 . Most SMS patients show neurological symptoms, mild-to-moderate intellectual disability, and strong long-term memory de cits 4 . Almost all (96%) SMS patients also show delayed speech and motor skills 5 , hyperphagia 6 , and sleep disturbance 7 .…”

“…Most SMS patients show neurological symptoms, mild-to-moderate intellectual disability, and strong long-term memory de cits 4 . Almost all (96%) SMS patients also show delayed speech and motor skills 5 , hyperphagia 6 , and sleep disturbance 7 . Sleep disturbance is one of the earliest diagnostic indicators of SMS, manifesting with frequent awakenings during night-time sleep and excessive daytime sleepiness 8 .…”