Schwartz-Jampel Syndrome Health Article

Definition

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.

Description

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

Genetic profile

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.