Smith-Magenis syndrome is a rare genetic disease that occurs when the short arm of the 17th chromosome is micro—damaged. Pathology is manifested by multiple congenital malformations, among which anomalies of the facial skeleton predominate, as well as intellectual disabilities, various behavioral features. Molecular genetic testing, neurological examination, and instrumental imaging methods are prescribed for the diagnosis of Smith-Magenis syndrome. Patients require the help of speech therapists, rehabilitologists, correctional teachers, according to indications, treatment of somatic complications is carried out.
Q93.5 Other chromosome part deletions
The syndrome is named after American clinician Ann Smith and cytogeneticist Ellen Magenis, who in 1980 first described a characteristic symptom complex in a group of children. Previously, it was believed that the disease occurs with a frequency of 1:25,000, but with the development of molecular genetic diagnostic methods, a higher prevalence was confirmed – 1:15,000. The pathology is most often observed in children with mental retardation — 1 case per 569 patients.
The disease occurs due to a spontaneous chromosomal anomaly — deletion of chromosome 17 at the 17p11.2 locus, which involves the loss of up to 4 million nucleotide pairs. Up to 25% of clinical cases of Smith-Magenis syndrome are atypical microdeletions, which are expressed in the loss of a smaller portion of the short arm of the chromosome. The disease is sporadic, while scientists have not been able to establish typical patterns and provoking factors.
The development of symptoms characteristic of the syndrome is primarily associated with a violation of the RAI1 gene, which is an inducer of retinolic acid. Scientists discuss its involvement in tissue differentiation, which explains the formation of multiple birth defects. Also, RAI1 is presumably used in the differentiation of neurons. Some mental manifestations of Smith-Magenis syndrome are caused by a defect in the synthesis and degradation of melanin.
Children have typical features of appearance, which are found already in infancy. They usually have a wide square head shape, a convex forehead, deep-set eyes with a Mongoloid cut. Also, the syndrome is characterized by underdevelopment of the middle zone of the face, a short nose with turned-out nostrils, a tent-shaped upper lip with a relatively small lower jaw. Children have disproportionately short arms and legs, and growth retardation is noted from an early age.
A specific diagnostic sign of Smith-Magenis syndrome is sleep disorders. In the first year of life, pathological drowsiness is observed, such children sleep a lot during the day, they have to be woken up for the next feeding. Over time, circadian rhythms are disrupted, late bedtime prevails with frequent night awakenings. With age, the patient sleeps more and more during the day, cannot sleep at night.
Neuropsychiatric changes include moderate mental retardation, which occurs in almost all patients. It is characterized by a delay in psychorechological development, difficulties in pronouncing words, attention deficit with hyperactivity. Up to 30% of patients have neurological disorders: movement coordination disorders, peripheral neuropathy, seizures.
Smith-Magenis disease is accompanied by a specific behavioral profile. Children suffer from stereotypical behavior, show maladaptive personality traits — outbursts of anger, disobedience, constant demand for attention from adults. Some patients are prone to self-harm: bite, pinch or beat themselves, inject foreign objects into the physiological openings of the body.
Most children have muscular hypotension from birth, as a result of which there are difficulties in feeding, swallowing disorders, refusal of food. In 80% of cases, Smith-Magenis syndrome is associated with ophthalmological problems: iris dysplasia, microcornea, Brushfield spots. More than 60% of patients suffer from chronic otitis media, conductive or sensorineural hearing loss. Half of the patients are diagnosed with hypercholesterolemia.
Heart defects occur in 25% of cases of the syndrome. The most common defects of the atrial and interventricular septa, tricuspid valve stenosis, tetrad of Fallot. Up to 15% of children suffer from urinary tract abnormalities, which include unilateral renal agenesis, doubling of the ureters, and an increase in the linear size of organs.
The examination is carried out by a multidisciplinary team of specialists with the participation of a pediatrician, a pediatric neurologist, a psychiatrist, and a geneticist. Smith-Magenis syndrome has pathognomonic phenotypic and behavioral signs, upon detection of which a preliminary diagnosis is established. The following methods are used to verify pathology:
- Genetic analysis. To detect the mutation, FISH hybridization with specific probes is used, which determines the pathology with an accuracy of 96-100%. If the test did not show Smith-Magenis syndrome in the presence of typical clinical signs, additional molecular analyses are performed.
- Prenatal diagnosis. With a burdened family history or alarming ultrasound results to exclude the syndrome, it is possible to study by amniocentesis in the second trimester of pregnancy. Given the spontaneous nature of the mutation, such a diagnosis is rarely made.
- Neurological examination. The patient needs a complete examination with an assessment of reflexes, muscle tone, tests for coordination of movements. Tests on the level of intelligence, the degree of development of cognitive functions are necessarily carried out. Often, the examination is supplemented by a psychiatric consultation.
- Instrumental visualization. Research methods are assigned differentially. Ophthalmoscopy, audiometry, and the study of induced auditory potentials may be required. To identify somatic disorders typical of the clinical picture of the syndrome, echocardiography, ultrasound of the abdominal cavity and retroperitoneal space are recommended.
An annual comprehensive examination of the state of health is shown to control the dynamics of disorders. An individual program of symptomatic therapy is selected for the patient. Medications are rarely prescribed, mainly for the correction of insomnia, and psychotropic drugs are not used because of the risk of aggravating mental problems. Treatment includes the following areas:
- Speech therapy help. At an early age, classes with a speech therapist are necessary to improve the state of the articulatory apparatus and structures of the oral cavity, which facilitates feeding, creates conditions for the development of speech. In the future, a long correction is required to improve verbal skills.
- Occupational therapy. Frequent problems with muscle tone and coordination of movements require the participation of rehabilitation specialists in the treatment program, who help restore motor functions, develop fine motor skills, improve visual and auditory perception.
- Correctional programs. Children with Smith-Magenis disease study well in small, quiet groups of up to 5-7 people, where everyone receives sufficient attention and support from a teacher. The curricula are selected taking into account the degree of intellectual disabilities.
With a complicated course of the syndrome, the treatment regimen expands. Neurological disorders require the use of physiotherapy, exercise therapy, antiepileptic drugs. To normalize vision, some people need optical correction, strabismus correction. Surgical treatment of heart defects is carried out in accordance with the identified anomaly.
Prognosis and prevention
With the timely initiation of complex therapy of Smith-Magenis syndrome, it is possible to significantly develop the patient’s motor and speech skills, adapt him to life in society. The prognosis is relatively favorable with lifelong rehabilitation, social and psychological support. Specific measures for the prevention of the syndrome have not been developed, due to its sporadic nature.