Smith-Magenis syndrome is a developmental disorder which affects several organs and systems of the body.
As previously stated, SMS signs might be very variable, especially in later life stages. Thus, each case might show a different clinical presentation and family members of affected children should discuss the details with the medical team.
Facial features appear to be very distinctive:
The jaw might appear noticeable small (micrognathia) early in life, but as the child ages the jaw begins to abnormally protrude outward (relative prognathia) together with the general progression of all SMS signs. In addition, secondary teeth, particularly premolars, might be absent while the other teeth might display enlarged pulp chambers and reduced roots (taurodauntism). These dental signs may be accompanied by an open bite posture characterized by a considerable tongue enlargement (macroglossia) and previous episodes of teeth grinding (bruxism).
SMS signs can involve other body parts as well. Muscle tone might appear diminished (hypotonia), a condition which is frequently coupled with the presence of poor reflexes (hyporeflexia). Infants may show difficulties in growing and gaining weight at the expected rate based upon gender and age, a condition known as failure to thrive. This further complication is often worsened due to feeding difficulties such as poor sucking ability. Speech delay may also be observed in this early phase, especially as infrequent crying and diminished vocalizations characterizing the infant behavior. Affected infants may also show a general state of lethargy along with the tendency of napping for prolonged periods at daytime. The digestive system may be effected too, as indicated by the repeated appearance of gastroesophageal refluxes.
Cognitive ability is cut back to a state of mild or moderate intellectual disability in affected individuals. These are strictly connected with behavioral problems such as head banging and self-hugging which appear very early in life. Other behavioral problems can be summed up as follows:
Other signs of aggression might involve behaviors such as face slapping, skin picking, and hand/wrist biting which can result in self-inflicted injuries. Fingernail and toenail yanking (onychotillomania) might appear in older children, which is frequently coupled with the tendency of inserting objects into the orifices of the body (polyembolokoilamania)   and an unusual capability of remembering faces, things, and places. It should be noted that despite the behavioral problems, affected individuals tend to show engaging personalities and a sense of humor.
Symptoms involving the ears and eyes include chronic ear infection, together with conductive hearing loss (occurring when sound wave conductivity problems arise) or increased sensitivity to particular sounds and frequencies. In regard to eye problems progressive nearsightedness (myopia), reduced cornea and crossed eyes (strabismus) are particularly frequent.
Signs might also involve larynx and its surrounding areas. Laryngeal abnormalities like polyps, nodules, and especially swelling, which results from edema, may be observed. Affected individual may experience difficulty of the mouth palate to properly close during speech (velopharyngeal insufficiency), or the problems in controlling lip, tongue, and jaw muscle movements often resulting in tongue protrusion. All these abnormalities commonly lead to vocal cord paralysis and contribute to speech delay development.
Weight gain and obesity tend to set in during adolescence, affecting 90% of children with SMS. In addition, high cholesterol levels and chronic constipation may be present. On the other hand, height seems to be seldom affected, with the majority of the patients maintaining a proper stature.
Sleep disturbances represent a life-long problem. They appear in early childhood and tend to continue in both adolescence and adulthood. Major sleep problems include difficulty in falling asleep, inability to enter into REM phase, shortening of sleep cycles, and frequent night awakening episodes. As a consequence, this might result in drowsiness during daytime associated with an inverted melatonin circadian rhythm (reported in around 90% of all cases).
Skeletal malformations often involve the spine, especially lordosis (front-to-back spine curvature) and scoliosis (sideway spine curvature). These appear frequently along with hand and feet abnormalities causing walking problems. Vertebral abnormalities and forearm and elbow limitations are rare but still significant. Other signs may suggest problems with other body systems, like:
SMS can be usually diagnosed by using the following techniques:
The main goal of SMS treatment is to treat and control symptoms as far as possible . SMS treatment includes:
The diet plays an important role and should be based on vegetarian foods and other healthy products. Paramount is also the melatonin treatment, in the attempt of restoring the impaired circadian rhythm and avoiding aggressive behavior resulting from it. This is usually coupled with the administration of anticonvulsant and antipsychotic drugs to cope with psychological complications. All in all, SMS treatment requires the involvement of a team made up of different professionals, such as genetic counselors, psychologists, speech therapists, and molecular biologists.
If SMS is diagnosed early in life, prognosis for the affected patients is very good, especially in terms of life expectancy. With the proper treatment provided on a regular basis, SMS patients might live up to 60 or 70 years, just as a normal person would.
The etiological factor of SMS is a deletion of the chromosome number 17, in a section which includes the retinoic acid-induced (RAI1) gene. RAI1 has been reported to play a pivotal role in many functions of the body, including those of the brain. Unfortunately, the precise role of this gene and its related protein has not been fully understood yet , while the cause of the chromosomal alteration, which appears to be spontaneous, is still unknown. The chromosome rearrangements which lead to the 7p11.2 deletion are sporadic, and this explains the rare occurrence of this disorder.
SMS has been identified all over the world, with no significant difference among human races. The incidence of SMS is estimated to be around 1 every 25.000 births, even though the actual prevalence is slightly higher than that, with a rate of around 1 every 15.000 births. Therefore, the disorder is sporadic, and neither recurrence in a family or germinal mosaicism has been observed.
It is interesting to notice that a great part of affected individuals identified to date is aged between 5 to 10 years.
The vast majority of SMS cases (around 90%) has been associated with the previously mentioned deletion of the chromosome 17 in the p11.2 position (17p11.2 deletion). Deletion is usually caused by irregularities in the chromosome recombination due to the presence of frequently repeated elements in the region concerned. In particular, the region p11.2 of the chromosome 17 is among the most recombination-prone locations, reported to be associated with other genetic diseases such as hereditary neuropathy with liability to pressure palsies and Charcot Marie Tooth disease type 1A. In around 70% of the cases, the deletion is usually caused by an unequal meiotic crossover following nonallelic recombination between the repeated elements flanking the deleted region called SMS REPs. In the remaining 30% of the cases, instead, the deletion is due to recombination between other repeated elements such as AT-rich repeats or Alu elements. Furthermore, in around 10% of all SMS cases the disorder is due to mutations occurring in the RAI1 gene.
As SMS is a congenital disorder, no particular measure can be suggested to prevent it.
Smith-Magenis syndrome (SMS) is a complex developmental disorder which affects a series of body organs and systems. It is characterized by some major signs such as particular facial features and mild to moderate intellectual disabilities, which in turn are usually associated with impaired speech or language skills and sleep or behavior problems.
Main facial features include a broad and square-shaped face, full cheeks, deep-set eyes and a prominent lower jaw. Furthermore, the middle of the face and the bridge of the nose appear clearly flattened. Another characteristic feature presents the mouth as turned downward, forming an outward-curving upper lip, as well as dental abnormalities. In early childhood, these facial differences are usually mild, but become more distinctive in later stages of life.
An affectionate and engaging personality is characteristic in individuals with SMS. Moreover, they often display fits of temper, anxiety, aggression, and impulsiveness. Common behavioral abnormalities include episodes of self-injury (e.g. head banging, skin picking), difficulty in paying attention, compulsively licking fingers and flipping book pages (a behavior known as "lick and flip"), and repeatedly hugging oneself. Disrupted sleep patterns may frequently be observed early in life, with the affected subjects sleeping at day but experiencing problems falling asleep at night.
Other signs may be:
Heart and kidney defects are reported less often     .
Smith-Magenis syndrome is a rare congenital disorder associated with a significant developmental delay. The genetic causes responsible for Smith-Magenis syndrome generally result in learning and behavioral difficulties together with characteristic disturbances in the sleep pattern.
The major features of Smith-Magenis syndrome are the characteristic developmental delay and the related learning difficulties, which might rage from a moderate to a severe level. Early in life, failure to thrive is particularly frequent, which is usually associated with the distinctive low tone of muscles, the typical feeding difficulty and the frequent ear infections. Another characteristic feature is speech delay, especially in terms of difficult language comprehension and expression, which is usually more pronounced than motor difficulty.
Typical facial features present as heavy brows, up-slanting eyes, flat and wide head linked to a prominent forehead, and a broad mouth characterized by upper lips with fleshy and inverted central portion. Key features can involve other body parts, like spine (scoliosis and lordosis), kidney, the immune system, and frequent episodes of peripheral neuropathy like decreased sensitivity to pain and temperature.
Behavioral problems represent another key feature of Smith-Magenis syndrome, which especially consist of self-injuries like self-pitching, hand biting, and scratching. These are then accompanied by psychological problems like a restless mental state, aggression, hyperactivity, frequent and prolonged tantrum episodes, and in general easy distractibility, which partially explains the learning difficulties of affected individuals. Sleep disturbances are also typical and usually tend to continue in more advanced ages. Autistic-type behaviors, like unwillingness to change, repetitive questioning and a marked preoccupation for particular topics may also be commonly observed.
Despite the behavioral and psychological difficulties, the character of affected children is often described as loving and caring, with a great sense of humor and a peculiar love for the attention and the interaction of adults.