Schwartz-Jampel syndrome – This is a hereditary disease that is expressed in multiple anomalies of the skeleton and is accompanied by failures in the process of neuromuscular excitability. Patients face difficulties in relaxing contracted muscles, against the background of their increased excitability (both mechanical and electrical), which is the main symptom of pathology.
The syndrome was first described in 1962 by two doctors: R. S. Jampel (neuro-ophthalmologist) and O. Schwartz (pediatrician). They observed two children – a brother and a sister aged 6 and 2 years. The children had symptoms characteristic of the disease (blepharophimosis, double row of eyelashes, bone deformities, etc.), which the authors associated with genetic abnormalities.
A significant contribution to the study of this syndrome was made by another neurologist D. Aberfeld, who pointed out the tendency of the pathology to progress, and also focused on neurological symptoms. In this regard, there are often such names of the disease as: Schwartz-Jampel syndrome, myotonia chondrodystrophic.
Schwartz-Jampel syndrome is recognized as a rare disease. Rare diseases are usually those diseases that are diagnosed no more than 1 case per 2000 people. The prevalence of the syndrome is a relative value, since the life of most patients is quite short, and the disease itself is very difficult and is often diagnosed by doctors who do not have knowledge in the field of hereditary neuromuscular pathology.
It has been established that most often the Schwartz-Jampel syndrome occurs in the Middle East, the Caucasus and South Africa. Experts attribute this fact to the fact that it is in these countries that the number of closely related marriages is higher than in the whole world as a whole. At the same time, gender, age, race have no effect on the frequency of occurrence of this genetic disorder.
Causes of Schwartz-Jampel Syndrome
The causes of Schwartz-Jampel syndrome are genetic disorders. It is assumed that this neuromuscular pathology is determined by an autosomal recessive type of inheritance.
Depending on the phenotype of the syndrome, experts identify the following causes of its development:
The classic type of Schwartz-Jampel syndrome is type 1A. Inheritance occurs according to an autosomal recessive type, the birth of twins with this pathology is possible. The HSPG2 gene, located on chromosome 1p34-p36,1, undergoes mutation. Patients produce a mutated protein that affects the functioning of receptors located in a variety of tissues, including muscle tissue. This protein is called perlecan. In the classical form of the disease, the mutated perlecan is synthesized in normal amounts, but it functions poorly.
Schwartz-Jampel syndrome type 1B. Inheritance occurs in an autosomal recessive manner, the same gene on the same chromosome, but perlecan is not synthesized in sufficient quantities.
Schwartz-Jampel syndrome type 2. Inheritance also occurs in an autosomal recessive manner, but the null LIFR gene, located on chromosome 5p13,1, mutates.
However, the reason why the muscles in Schwartz-Jampel syndrome are in constant activity at this point in time is not well understood. It is believed that mutated perlecan disrupts the function of muscle cells (their basement membranes), but the occurrence of skeletal and muscle abnormalities has not yet been explained. In addition, another syndrome (Stuva-Wiedemann syndrome) has a similar symptomatology in terms of muscle defects, but perlecan is not affected. In this direction, scientists still continue to conduct active research.
Symptoms of the Schwartz-Jampel syndrome
The symptoms of Schwartz-Jampel syndrome were isolated from all available case reports in 2008.
The clinical picture is characterized by the following features:
The patient’s height is below average;
Prolonged tonic muscle spasms that occur after voluntary movements;
Face frozen, “sad”;
The lips are compressed tightly, the lower jaw is small;
The palpebral fissures are narrow;
The hairline is low;
The face is flattened, the mouth is small;
Joint movements are limited – this applies to the interphalangeal joints of the feet and hands, the spinal column, femoral joints, wrist joints;
Muscle reflexes are reduced;
Skeletal muscles are hypertrophied;
The vertebral table is shortened;
The neck is short;
Diagnosed with hip dysplasia;
There is osteoporosis;
The arches of the feet are deformed;
The voice of the sick is thin and high;
Vision is impaired, the palpebral fissure is shortened, the eyelids at the outer corner of the eye are fused, the cornea is small, there is often myopia and cataracts;
Eyelashes are thick, long, their growth is disordered, sometimes there are two rows of eyelashes;
The ears are set low;
Often a hernia is found in children – inguinal and umbilical;
Boys have small testicles;
The gait is waddling, duck, often there is a clubfoot;
While standing and while walking, the child is in a half-squat;
The patient’s speech is fuzzy, unclear, salivation is characteristic;
Mental faculties are disturbed;
There is a lag in growth and development;
Bone age is less than passport age.
In addition, the symptoms of Schwartz-Jampel syndrome differ depending on the phenotype of the disease:
Phenotype 1A is a symptom
The 1A phenotype is characterized by an early manifestation of the disease. This occurs before the age of 3 years. The child has moderate swallowing and breathing difficulties. There are contractures on the joints, which can be present both from birth and be acquired. The patient’s hips are short, kyphoscoliosis and other anomalies in the development of the skeleton are pronounced.
The mobility of the child is low, which is explained by the difficulties in performing movements. The face is motionless, reminiscent of a mask, the lips are compressed, the mouth is small.
The muscles are hypertrophied, especially the muscles of the thighs. When treating children with the classic course of Schwartz-Jampel syndrome, one should take into account the high risk of developing anesthetic complications, especially malignant hyperthermia. It occurs in 25% of cases and is fatal in 65-80% of cases.
Mental impairment ranges from mild to moderate. At the same time, 20% of such patients are recognized as mentally retarded, although there are descriptions of clinical cases when the intelligence of people was quite high.
A decrease in myotonic syndrome is observed when taking Carbamazepine.
Phenotype 1B is a symptom
The disease develops in infancy. Clinical signs are similar to those observed in the classical variant of the course of the disease. The difference is that they are more pronounced. First of all, this concerns somatic disorders, especially the patient’s breathing suffers.
Skeletal anomalies are more severe, the bones are deformed. The appearance of patients resembles patients with Knist syndrome (shortened torso and lower limbs). The prognosis for this phenotype of the disease is unfavorable, often patients die at an early age.
Phenotype 2 is a symptom
The disease manifests itself at the birth of a child. The long bones are deformed, the growth rate is slowed down, the course of the pathology is severe.
The patient is prone to frequent fractures, muscle weakness, respiratory and swallowing disorders are characteristic. Children often develop spontaneous malignant hyperthermia. The prognosis is worse than with phenotypes 1A and 1B, the disease most often ends with the death of the patient at an early age.
Features of the clinical course of the disease in childhood:
On average, the disease debuts in the first year of a child’s life;
The child has difficulty sucking (begins to suck after a certain period of time after being attached to the breast);
Motor activity is low;
It can be difficult for a child to immediately pick up an object that he is holding from his hands;
Intellectual development can be preserved, violations are observed in 25% of cases;
Most of the patients successfully graduate from school, and the children attend a general educational institution, and not specialized educational institutions.
Diagnosis of the Schwartz-Jampel syndrome
Perinatal diagnosis of Schwartz-Jampel syndrome is possible. For this, ultrasound of the fetus is used, during which skeletal anomalies, polyhydramnios, and impaired sucking movements are detected. Congenital contractures can be visualized at 17-19 weeks of gestation, as well as shortening or deformity of the hip.
Biochemical analysis of blood serum gives a slight or moderate increase in LDH, AST and CPK. But against the background of independently developing or provoked malignant hyperthermia, the level of CPK increases significantly.
To assess muscle disorders, electromyography is performed, and changes will be noticeable already when the child reaches six months of age. A muscle biopsy is also possible.
Kyphosis of the spine, osteochondrodystrophy is diagnosed by X-ray examination. Lesions of the musculoskeletal system are clearly visible during MRI and CT. It is these two diagnostic methods that are used most often by modern doctors.
It is important to make a differential diagnosis with such diseases as: Knist’s disease, Pyle’s disease, Rolland-Desbuquois dysplasia, congenital myotonia of the first type, Isaacs syndrome. Distinguishing pathologies allows such a modern diagnostic method as genetic DNA typing.
Treatment of Schwartz-Jampel syndrome
At the moment, there is no pathogenetic treatment of the Schwartz-Jampel syndrome. Doctors recommend that patients adhere to the daily routine, limit or completely eliminate physical overstrain, as it is the most powerful factor stimulating the progression of the pathology.
As for the rehabilitation of patients, these activities are selected on an individual basis and will vary depending on the stage of the disease. Patients are recommended physiotherapy exercises with dosed and regular physical activity.
As for nutrition, you should exclude foods that contain a large amount of potassium salts in their composition – these are bananas, dried apricots, potatoes, raisins, etc. The diet should be balanced, rich in vitamins and fiber. Dishes should be offered to the patient in the form of puree, in liquid form. This will minimize the difficulties with chewing food that occur as a result of spasm of the facial muscles and masticatory muscles. In addition, one should be aware of the risk of aspiration of the airways with a food bolus, which can lead to the development of aspiration pneumonia. Also, the progression of the disease is influenced by the use of cold drinks and ice cream, bathing in cold water.
The benefits of physiotherapy for the treatment of the syndrome should not be underestimated.
Schwartz-Jampel. Tasks assigned to the physiotherapist:
Reducing the severity of miotic manifestations;
Training of the extensor muscles of the legs and arms;
Stopping or slowing down the formation of bone and muscle contractures.
Various baths (salt, fresh, coniferous) lasting 15 minutes daily or every other day are effective. Useful are local baths with a gradual increase in water temperature, ozocerite and paraffin applications, exposure to infrared rays, gentle massage and other procedures.
Recommendations regarding spa treatment are as follows: travel to areas whose climate is as close as possible to the usual conditions in which the patient lives, or visit areas with a mild climate.
To reduce the severity of the symptoms of the disease, the following medications are indicated:
Antiarrhythmic agents: Quinine, Diphenine, Quinidine, Quinora, Cardioquin.
Acetazolamide (Diacarb), taken orally.
Anticonvulsants: Phenytoin, Carbamazepine.
Botulinum toxin administered topically.
Muscle nutrition is maintained by taking vitamin E, selenium, taurine, coenzyme Q10.
With the development of bilateral blepharospasm and in the presence of bilateral ptosis, patients are recommended ophthalmic surgery. Progressive bone deformities, the occurrence of contractures – all this leads to the fact that patients will have to go through several orthopedic operations. Due to the risk of developing malignant hyperthermia in childhood, drugs are administered rectally, orally or intranasally. The operation without fail requires preliminary sedation with barbiturates or benzodiazepines.
The classical course of the disease according to phenotype 1A does not have a significant effect on the life expectancy of the patient. The risk of having a child in a family with a burdened history is equal to 25%. Patients need psychological and social support. In addition, the patient should be led by such specialists as: a geneticist, a cardiologist, a neurologist, an anesthesiologist, an orthopedist, a pediatrician. If there are speech disorders, then classes with a speech pathologist-defectologist are shown.