Schwartz-Jampel syndrome (SJS) is a rare, inherited condition of the skeletal and muscle systems that causes short stature, joint limitations, and particular facial features.
First described in 1962, SJS is now a clearly defined syndrome that is divided into two types. Type 1A is the classical form that develops in early childhood, usually between the first and third year of life. Type 1B is less common but more severe and its symptoms are present at birth. Both types of SJS involve generalized disease of the muscles called myopathy. The muscles tend to be quite stiff and are unable to relax normally. This is a condition known as myotonia. The myotonia causes many joints in the body to stay in a bent or flexed position (joint contractures).
In addition to muscle problems, the bones in the skeleton do not develop normally and this is why SJS may also be called a type of skeletal dysplasia . Abnormal bone shape and poor bone growth result in decreased total height, incorrect arm and leg postures, as well as curving of the spine (scoliosis ).
Unique facial features of SJS include narrow eye openings with drooping eye lids, a small mouth, and puckered lips. These features are also due to the stiffness of the muscles that support the face and individuals with SJS appear to have a fixed facial expression.
Persons affected with SJS often have normal intelligence, although varying degrees of mental retardation may affect as many as 25% of patients. However, the myotonia may lead to poor speech articulation and drooling so that affected individuals are sometimes misdiagnosed as having mental retardation.
Respiratory and feeding difficulties are frequent with SJS Type 1B due to the more severe nature of the muscle and bone disease. These problems may be fatal in early infancy. Persons with SJS Type 1A have a much longer life expectancy, although this depends on how their disease progresses.
SJS has also been referred to as:
- myotonic myopathy, dwarfism, chrondrodystrophy, and ocular and facial abnormalities
- Schwartz-Jampel-Aberfeld syndrome
- Schwartz syndrome
- Aberfeld syndrome
- chrondrodystrophic myotonia
- osteochondromuscular dystrophy
- spondylo-epimetaphyseal dysplasia with myotonia
Both types of SJS are known to be inherited in an autosomal recessive manner. This was concluded after the following observations were made. SJS affects males and females alike. Parents of affected individuals rarely show any signs or symptoms of SJS. Parents have been reported to have more than one affected child. Consanguineous relationships were seen in some families.
Genetic studies of many families revealed that all cases of SJS were linked to an area on chromosome one, described as 1p36.1. A gene in this region, named HSPG2, makes a protein called perlecan that is thought to play the primary role in causing SJS. The function of the perlecan protein is not completely understood. However, it has an important job in the cells of the body's connective tissue (bone, cartilage, muscles, ligaments, tendons and blood vessels). As of the year 2001, studies have shown that perlecan helps keep cartilage and bone strong and are essential for certain chemical processes in the muscle tissue. It is also thought that perlecan helps to direct the normal growth of some cells.
The gene for perlecan (HSPG2) is fairly large and mistakes or mutations in the instructions of the gene have been found in some persons with SJS. These gene mutations change how the perlecan protein is made and usually prevents it from doing its normal job in the muscles and bones of the body. The effects of these HSPG2 gene mutations cause SJS.
The location 1p36.1 means that the gene is near the top or end of the short arm of chromosome number one. A human being has 23 pairs of chromosomes in nearly every cell of their body. One of each kind (23 total) is inherited from the mother and another of each kind (23 total) is inherited from the father, for a total of 46. One chromosome may hold hundreds to thousands of individual genes and as the chromosomes exist in pairs, so do the genes. Therefore, every person has two copies of the HSPG2 gene that makes perlecan. Individuals that have a diagnosis of SJS are thought to have a mutation in both copies of their HSPG2 gene, each of which was inherited from one of their parents. Unaffected parents of children with SJS are therefore carriers for SJS. Their one normal HSPG2 gene appears to make enough perlecan so those carriers do not show any symptoms of SJS. Most parents do not know that they are carriers for SJS until they have an affected child. When both parents are carriers for the same autosomal recessive disease such as SJS, there is a 25% chance with each and every pregnancy that they have together that their child will inherit both mutated HSPG2 genes and develop SJS.
SJS is a very rare genetic syndrome that affects males and females in many ethnic backgrounds. The exact incidence is unknown. Approximately 100 cases have been reported in scientific publications as of the year 2001. This may not accurately reflect the incidence of SJS, as some persons may not come to medical attention or may be misdiagnosed.
Signs and symptoms
A child born with SJS Type 1A may show no outward signs of the condition at birth. Over the following one to three years, progressive myotonia of the muscles and resulting joint contractures develop. The typical bone problems become obvious and growth in height slows down. These symptoms are evident at birth in children with SJS Type 1B. The following descriptions apply to both SJS Type 1A and Type 1B. However, each person with SJS may be affected to a different degree and their kinds of symptoms may vary.
Head and neck
Myotonia of the muscles in the face causes a tight and fixed facial expression. The eye openings are almost always narrowed and small and the upper and lower eyelids are not joined properly at the corners of the eye (blepharophimosis). The upper eyelid may also appear droopy (ptosis). Nearsightedness (myopia ) is present in 50% of patients and occasionally cataracts and lens dislocation may develop in the eye. The mouth is small and lips are puckered due to tight facial muscles. This may lead to speech difficulty. The chin may also be small or set back.
Hernias of the groin and navel areas are often noticed at birth. A hernia is the bulging of a tissue outside of its normal space and a simple operation can usually place it back inside. Pectus carinatum is a common bony deformity of the chest that causes the breast bone to protrude forward. Abnormalities in the growth and development of the bones of the spinal column (vertebrae) lead to scoliosis that usually worsens with age. Development of puberty is most often normal for persons with SJS.
Some babies with SJS are born with a dislocation of their hip joint. This is common in infants without SJS as well. As the muscle disease of SJS progresses, the joints become very stiff. The hips, knees and elbows in particular have very limited range of motion. These joint contractures worsen until puberty and then tend to stay the same from that point on. Eventually, a wheelchair is needed due to significant limitation of movement. The long bones in the body (i.e.: the thighbone) are bowed and shortened. This can cause a person with SJS to waddle as they walk and to stand in a crouching position. Therefore, an individual with SJS tends to be shorter than 90% of unaffected persons their age. A few have been reported to reach average height. Typically, their arms and legs have an increased amount of body hair as well.
The muscles of the body show progressive myotonia, as they remain tight and are unable to relax normally. The muscle bulk may be increased in some areas, such as the thighs, and may waste away in others. As the muscles are unable to function normally, physical activity is restricted and a person may tire very easily.
Central nervous system and behavior
Most individuals with SJS have normal intelligence, although some degree of mental retardation has been reported. Developmental language problems and attention difficulties have also been seen in some cases. Reflexes tend to be slower than normal. A high-pitched voice and drooling may be noticed due to muscle stiffness in the mouth and throat area. This may cause feeding difficulties and choking may be of concern.
The diagnosis of SJS Type 1A or Type 1B is made mainly by the presence of the symptoms described above. There is no specific biochemical or muscle testing that confirms a suspected diagnosis. Although research studies have identified mutations in the HSPG2 gene in some families, widespread genetic testing is not clinically available as of the year 2001. Such genetic mutations may be unique to each family and therefore may not be found in other persons affected with SJS.
Several different studies may be performed to determine the type and severity of muscle disease when considering a diagnosis of SJS. This may include a muscle biopsy that samples a piece of muscle and examines the appearance of the muscle cells. A muscle biopsy may appear normal or it may show signs of myopathy. A particular chemical, called creatine kinase, can be measured in a person's blood. Very high levels of creatine kinase usually indicate the presence of muscle disease or wasting. An electromyogram (EMG) is a test that measures the electrical currents made within an active muscle. The EMG pattern is usually abnormal in persons with SJS. These tests will confirm the presence of muscle disease but there are no specific changes in any of them that are unique to SJS.
The following are some abnormalities of the bones that are frequently noticed on x rays:
- flat and irregularly formed vertebrae
- deformity of the upper part of the thigh bone
- a flattened joint socket where the hip and thigh bone meet
- specific changes in the development of the bones in the hand
- bowing of the long bones, especially the leg bones
- curvature of the spine that causes a hunchback appearance
Many of the symptoms of SJS are also present in other conditions and it is important to distinguish SJS from the following disorders:
- Stuve-Wiedemann syndrome (which was previously called SJS Type 2 until it was determined that they were the same condition)
- Freeman-Sheldon syndrome (also known as whistling face syndrome)
- Marden-Walker syndrome
- Kniest dysplasia
- Seckel syndrome
- myotonic dystrophy
- the mucopolysaccharidoses
Treatment and management
There is not a cure for SJS. The treatment involves managing the symptoms of the condition as they develop and supporting the needs of the individual as the disability progresses. Several medical specialists may monitor a person with SJS for particular symptoms or complications. An orthopedic doctor manages the abnormal bone development and may offer surgical options for treatment of hip dislocation, scoliosis or bone curvature. An ophthalmologist monitors eye problems such as nearsightedness and cataracts, for which glasses and surgery may be available. Cosmetic repair of blepharophimosis by plastic surgery may also be considered.
For those with a mental deficiency, special education programs with options for activities in regular classrooms may offer the best opportunities for learning. Physical therapy may help maintain the greatest possible range of motion of the joints and speech therapy may improve speech problems due to a small and tight mouth. Physical activities of children are usually limited due to their stiff joints. As the condition progresses, persons with SJS are often wheelchair-bound by their teenage years and occupational therapy may help improve their everyday living skills. Adults who live independently may require some assistance with everyday tasks that their disability prevents them from doing, such as household chores or even bathing.
Individuals with SJS can live well into adulthood despite progressive disability but the average life expectancy is unclear. They are usually wheelchair-bound by their teenage or young adult years. Although puberty development may be normal, no reports have been made of an individual with SJS fathering children or carrying a pregnancy.
SJS Type 1B may be fatal in the newborn period due to serious respiratory and feeding problems. As the muscles in the face and neck may be very tight, it can be difficult to place a tube down the throat (intubation) to allow a baby to breathe. Feeding may be a continuous struggle due to problems with or an inability to swallow.
Both types of SJS cause persons to be more prone to develop chest infections and pneumonia. There is also an increased risk for complications from anesthesia, specifically malignant hyperthermia (MH). MH is an abnormal chemical reaction in the body to the use of some anesthesia medications. It causes high fevers, breathing difficulty, rigid muscles and general serious illness. This condition may be life threatening.
Spranger, J., et al. "Spectrum of Schwartz-Jampel Syndrome Includes Micromelic Chondrodysplasia, Kyphomelic Dysplasia, and Burton Disease." American Journal of Medical Genetics 94 (2000): 287–295.
International Center for Skeletal Dysplasia. Saint Joseph's Hospital, 7620 York Rd., Towson, MD 21204. (410) 337-1250.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
Genetic Alliance. <http://www.geneticalliance.org>.
National Institute of Child Health and Human Development. <http://www.nichd.nih.gov>.
Jennifer Elizabeth Neil, MS, CGC
"Schwartz-Jampel Syndrome." Gale Encyclopedia of Genetic Disorders. . Encyclopedia.com. (November 20, 2018). https://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/schwartz-jampel-syndrome
"Schwartz-Jampel Syndrome." Gale Encyclopedia of Genetic Disorders. . Retrieved November 20, 2018 from Encyclopedia.com: https://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/schwartz-jampel-syndrome