About smith-magenis chromosome region

What is smith-magenis chromosome region?

Smith-Magenis syndrome is characterized by particular facial features, developmental delays, mental retardation and behavioral abnormalities.

The facial features include a broad square-shaped face, an abnormally short, broad head (brachycephaly); an abnormally broad, flat midface; a broad nasal bridge; an unusually prominent jaw (prognathism); eyebrows growing across the base of the nose (synophrys); a short full tipped nose and fleshy upper lip with a tented appearance.

Developmental delays and intelligence are variable but most affected individuals have mild to moderate mental retardation. Behavioral abnormalities include sleep disturbances, repetitive movements (stereotypies) and a tendency to inflict harm on oneself.

What are the symptoms for smith-magenis chromosome region?

Smith-Magenis syndrome is a highly variable disorder. The specific symptoms present and the overall severity of the disorder can vary from one person to another. It is important to understand that affected individuals will not have all of the symptoms discussed below and that every individual case is unique. Parents should talk to the physician and medical team about their child’s specific case, associated symptoms and overall prognosis.

Many individuals with SMS have Distinctive facial features including a broad, square-shaped facial appearance, a prominent forehead, deep-set eyes that are farther apart than usual (hypertelorism), an upslanting palpebral (eye) fissures, a broad bridge of the nose, hair growth between the eyebrows so it appears as one long eyebrow (synophrys), a down-turned (everted; cupid bow) upper lip, a short, full-tipped nose, and underdevelopment of the middle portion of the face (midface retrusion). The head may appear disproportionately Short (brachycephaly). Some affected infants may have an abnormally Small jaw (micrognathia) and the facial appearance is more “cherubic” with rosy cheeks. As affected individuals age, micrognathia may change so that the lower jaw abnormally protrudes outward (relative prognathia). In general, the Distinctive facial features associated with SMS progress with age. Affected individuals may also exhibit absence (agenesis) of secondary (permanent) teeth, particularly premolars, and taurodauntism, a condition characterized by enlargement of the pulp chambers and reduction of the roots of teeth; open bite posture with Large tongue (macroglossia) and history of bruxism (teeth grinding) are also common.

Infants usually have Diminished muscle tone (hypotonia), poor reflexes (hyporeflexia), and Feeding difficulties such as poor sucking ability, which can contribute to failure to thrive. Failure to thrive is defined as the failure to grow and gain weight at a rate that would be expected based upon age and gender. Infants are generally quiet and complacent with infrequent Crying and diminished vocalizations reflecting the marked early expressive speech delay. In addition, affected infants may nap for prolonged periods of time and exhibit generalized daytime lethargy. Gastroesophageal Reflux is also common during infancy.

Individuals with SMS have varying degrees of cognitive ability. Many individuals exhibit mild to moderate intellectual disability. Affected individuals often exhibit delays in attaining speech and motor skills and in reaching developmental milestones (developmental delays). Expressive language is often more delayed than receptive language skills.

Specific Behavioral problems (maladaptive behaviors) occur in children with SMS. A common initial sign is head banging during early childhood. Frequent upper body squeezes often described as “self-hugging” is also common. Affected children may also display impulsivity, Hyperactivity and attention deficient disorder, frequent and prolonged tantrums, sudden mood changes, toilet training difficulties, disobedience, and aggressive or attention-seeking behaviors. In addition to head banging, affected children may develop other self-injurious behavior such as hand biting, face slapping, skin picking, and wrist biting. Repeated head banging can potentially cause detachment of the retina, which although a concern, is not a high risk. Older children may yank at fingernails and toenails (onychotillomania) or insert objects into body orifices (polyembolokoilamania). Affected children tend to be excitable and easily distracted. Although Behavioral issues are common, many individuals tend to have endearing and engaging personalities, with great senses of humor, and facile long-term memory for faces, places and things.

Affected children may experience chronic ear infections, including repeated middle ear infections (otitis media). Hearing loss is very common, typically ranging from slight to mild in degree and showing a pattern of fluctuating and progressive hearing decline with age. Both conductive and/or sensorineural Hearing loss may develop. Conductive Hearing loss is most common in early childhood (under 10 years), while sensorineural Hearing loss occurs more frequently at older ages (11years – adulthood). Conductive Hearing loss develops when sound waves are inappropriately conducted through the external or middle ear to the inner ear, resulting in decreased sensitivity to sound. Sensorineural Hearing loss develops where there is damage to the inner ear (cochlea) or the nerve pathway from inner ear to the brain. Some affected children may be abnormally sensitive to certain sounds or frequencies (hyperacusis). Frequent sinus infections (sinusitis) are also common. Eye abnormalities such as progressive nearsightedness (myopia), crossed eyes (strabismus), and unusually smallness of the cornea (microcornea) may also occur.

Affected children often have abnormalities affecting the larynx (voice box) or surrounding tissue. Laryngeal abnormalities include the formation of polyps and nodules or swelling due to fluid retention (edema). Paralysis of the vocal cords has also developed. Affected children may experience velopharyngeal insufficiency, in which the soft palate of the mouth does not close properly during speech. Oral sensorimotor dysfunction, in which affected individuals have difficulties controlling the lips, tongue and jaw muscles, may also develop and can cause tongue protrusion and frequent drooling. Due to such abnormalities, children may develop a hoarse, deep voice. These abnormalities also contribute to delays in speech development.

Excessive weight gain and obesity may be seen in adolescence and approximately 90% of children may be Overweight or obese by the age of 14. Affected individuals may exhibit Short stature during childhood, although height is typically within the normal range as adults. Approximately 50% of children may have unusually high levels of cholesterol in the blood (hypercholesterolemia). Chronic constipation is also a frequent complication.

The sleep disturbance that occurs in affected individuals is a chronic lifelong problem. In addition to sleep issues during infancy (generalized Lethargy & “too sleepy”), affected individuals develop significant Sleep disturbances from early childhood that continue into adolescence and adulthood. The sleep cycle is characterized by problems that can include difficulty falling asleep, shortened sleep cycles, an inability to enter REM sleep and frequently awaking during the night and early in the morning (5:30-6:30AM). In general, the hours of sleep are less than expected for age. As a consequence of the disrupted nighttime sleep cycle affected individuals may exhibit periods of drowsiness during the day, known as excessive daytime sleepiness or sleep debt, which remains a chronic issue. The sleep abnormalities are associated with an inverted circadian rhythm of melatonin, reported in over 90% of studied cases. A circadian rhythm sleep disorder occurs when a person’s biological clocks fails to synchronize to a normal 24-hour day. Specifically, melatonin, a normal occurring hormone, rises and falls; it rises, peaking at night and causes drowsiness. Melatonin levels lessen in the morning, reaching their lowest levels during the middle of the day. In individuals with an inverted circadian rhythm, the rising and falling of melatonin levels is reversed (daytime highs).

Skeletal malformations are common in individuals with SMS and can include front-to-back curvature of the spine (lordosis), mild-to-moderate sideways curvature of the spine (scoliosis), abnormally small hands and feet, and markedly flat or highly arched feet that can cause an unusually manner of walking (abnormal broad-based gait). In rare cases, affected children have vertebral anomalies and forearm and elbow limitations.

Less often, other symptoms or physical findings have occurred in individuals with SMS including immune system dysfunction, thyroid function abnormalities (hypothyroidism), heart (cardiac) defects, kidney (renal) and/or urinary tract malformations, cleft lip and cleft palate, and seizures. Seizure activity can occur subtly so that seizure goes unnoticed (subclinical seizures). Peripheral neuropathy, which is a general term for any disorder of the peripheral nervous system, may also occur. Peripheral neuropathy encompasses any disorder that primarily affects the nerves outside the central nervous system (i.e. brain and spinal cord). Symptoms may include a decreased sensitivity to Pain commonly seen in SMS. Peripheral neuropathy is often associated with the loss of sensation or abnormal sensations such as tingling, burning, or pricking along the affected nerves, but it is unknown whether this occurs in individuals with SMS.

What are the causes for smith-magenis chromosome region?

In approximately 90% of affected individuals, a portion of the short arm (p) of chromosome 17 (17q11.2) is missing, which is referred to as deleted or monosomic. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 17p11.2” refers to band 11.2 on the short arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

In individuals with SMS, the deleted section of chromosome 17 includes the retinoic acid-induced 1 (RAI1) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a gene is missing due to a monosomic chromosome abnormality, the protein product of that gene is reduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. The specific functions of the protein produced (encoded) by the RAI1 gene are not fully understood.

The exact cause of the chromosomal alteration in SMS is unknown. The medical literature has indicated that virtually all documented cases appear to be due to a spontaneous (de novo) genetic change that occurs for unknown reasons.

In rare cases, SMS is the result of an error during very early embryonic development due to a chromosomal balanced translocation in one of the parents. A translocation is balanced if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes. If a chromosomal rearrangement is balanced, it is usually harmless to the carrier. However, they may be associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. In these cases, the clinical features of children may be influenced by additional imbalances of other chromosomes than 17. Chromosomal testing can determine whether a parent has a balanced translocation. In parents with a child with SMS who have a normal chromosome analysis the risk of recurrence in a future pregnancy is below 1%.

The remaining 10% of cases of SMS are caused by mutations in the RAI1 gene. These mutations may occur randomly with no family history (i.e. new mutation) or be inherited in an autosomal dominant manner. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. Mutations in the RAI1 gene lead to insufficient levels of functional copies of the protein product normally produced by the gene.

In two families reported in the medical literature, SMS occurred because of germline mosaicism. In germline mosaicism, some of a parent’s reproductive (germ) cells carry the RAI1 gene mutation or chromosome 17p deletion, while other germ cells do not (mosaicism). In addition, the other cells of a parent also do not have either to these chromosomal abnormalities; consequently, the parents are unaffected. However, as a result, one or more of the parent’s children may inherit the germ cell with a chromosomal abnormality, leading to the development of SMS. Germline mosaicism is suspected when apparently unaffected parents have more than one child with the disorder. The likelihood of a parent passing on a mosaic germline chromosomal abnormality to a child depends upon the percentage of the parent’s germ cells that have the abnormality versus the percentage that do not. There is no test for germline mutation or chromosome abnormality prior to pregnancy. Testing during pregnancy may be available and is best discussed with a genetic specialist.

A child born to an individual with SMS is at a theoretical risk of 50% to inherit the deletion or RAI1 mutation that causes the disorder. The fertility in SMS in general is not fully understood; however, there is at least one report in the medical literature of a mother with SMS having a child with SMS.

What are the treatments for smith-magenis chromosome region?

Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, dental specialists, speech pathologists, audiologists, ophthalmologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan and affect child’s treatment. Genetic counseling is of benefit for affected individuals and their families. Psychosocial support for the entire family is essential as well.

Treatment is symptomatic and supportive. Early intervention is important in ensuring that affected children reach their highest potential. Services that may be beneficial include special remedial education, speech/language therapy, physical therapy, occupational therapy, and sensory integration therapy, in which certain sensory activities are undertaken in order to help regulate a child’s response to sensory stimuli. Additional medical, social and vocational services may be recommended when appropriate.


Because of the highly variable nature of SMS, it is impossible to generalize about prognosis for individual cases. Some affected individuals have been able to become employed and even live semi-independently with support from family and friends. However, others require constant care and may need to live with family or in a residential facility. As stated above, parents should talk to the physician and medical team about their child’s specific case and overall prognosis.

What are the risk factors for smith-magenis chromosome region?

Smith-Magenis syndrome affects males and females in equal numbers. The incidence is estimated to be 1 in 15,000-25,000 people in the general population in the United States. However, cases may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of SMS in the general population. SMS has been reported throughout the world and in all ethnic groups.

Is there a cure/medications for smith-magenis chromosome region?

Certain medications may be used to treat behavioral problems such as attention deficit or hyperactivity. Specific medications have also been used to treat sleep disorders potentially associated with SMS. Melatonin supplementation, in order to normalize melatonin levels, taken at bedtime has shown benefit in anecdotal reports. Use of the B-blocker acebutolol in the morning to inhibit/suppress daytime melatonin secretion has shown some benefit in one French study.

Feeding difficulties require identification and appropriate therapy. Additional treatment follows standard guidelines for the specific symptom. For example, anti-seizure medications (anti-convulsants) may be used to treat seizures.

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